Sample records for tal og tale

  1. Revisiting the TALE repeat.

    PubMed

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

  2. Ostéogénèse imparfaite létale: diagnostic antenatal

    PubMed Central

    El Mhabrech, Houda; Zrig, Ahmed; Mazhoud, Ines; Njim, Leila; Hajjeji, Aouatef; Faleh, Raja; Hafsa, Ch

    2016-01-01

    L'ostéogenèse imparfaite (OI) est un groupe hétérogène de maladies affectant le collagène de type I et caractérisées par une fragilité osseuse. Les formes létales sont rares et se caractérisent par une micromélie avec déformation des membres. Un diagnostic anténatal d'OI létale a été fait dans deux cas, par échographie à 17 et à 25 semaines d'aménorrhée, complélées par un scanner du squelette fœtal dans un cas. Une interruption thérapeutique de grossesse a été indiquée dans les deux cas. PMID:28292051

  3. Non-RVD mutations that enhance the dynamics of the TAL repeat array along the superhelical axis improve TALEN genome editing efficacy

    PubMed Central

    Tochio, Naoya; Umehara, Kohei; Uewaki, Jun-ichi; Flechsig, Holger; Kondo, Masaharu; Dewa, Takehisa; Sakuma, Tetsushi; Yamamoto, Takashi; Saitoh, Takashi; Togashi, Yuichi; Tate, Shin-ichi

    2016-01-01

    Transcription activator-like effector (TALE) nuclease (TALEN) is widely used as a tool in genome editing. The DNA binding part of TALEN consists of a tandem array of TAL-repeats that form a right-handed superhelix. Each TAL-repeat recognises a specific base by the repeat variable diresidue (RVD) at positions 12 and 13. TALEN comprising the TAL-repeats with periodic mutations to residues at positions 4 and 32 (non-RVD sites) in each repeat (VT-TALE) exhibits increased efficacy in genome editing compared with a counterpart without the mutations (CT-TALE). The molecular basis for the elevated efficacy is unknown. In this report, comparison of the physicochemical properties between CT- and VT-TALEs revealed that VT-TALE has a larger amplitude motion along the superhelical axis (superhelical motion) compared with CT-TALE. The greater superhelical motion in VT-TALE enabled more TAL-repeats to engage in the target sequence recognition compared with CT-TALE. The extended sequence recognition by the TAL-repeats improves site specificity with limiting the spatial distribution of FokI domains to facilitate their dimerization at the desired site. Molecular dynamics simulations revealed that the non-RVD mutations alter inter-repeat hydrogen bonding to amplify the superhelical motion of VT-TALE. The TALEN activity is associated with the inter-repeat hydrogen bonding among the TAL repeats. PMID:27883072

  4. Designer TAL effectors induce disease susceptibility and resistance to Xanthomonas oryzae pv. oryzae in rice.

    PubMed

    Li, Ting; Huang, Sheng; Zhou, Junhui; Yang, Bing

    2013-05-01

    TAL (transcription activator-like) effectors from Xanthomonas bacteria activate the cognate host genes, leading to disease susceptibility or resistance dependent on the genetic context of host target genes. The modular nature and DNA recognition code of TAL effectors enable custom-engineering of designer TAL effectors (dTALE) for gene activation. However, the feasibility of dTALEs as transcription activators for gene functional analysis has not been demonstrated. Here, we report the use of dTALEs, as expressed and delivered by the pathogenic Xanthomonas oryzae pv. oryzae (Xoo), in revealing the new function of two previously identified disease-related genes and the potential of one developmental gene for disease susceptibility in rice/Xoo interactions. The dTALE gene dTALE-xa27, designed to target the susceptible allele of the resistance gene Xa27, elicited a resistant reaction in the otherwise susceptible rice cultivar IR24. Four dTALE genes were made to induce the four annotated Xa27 homologous genes in rice cultivar Nipponbare, but none of the four induced Xa27-like genes conferred resistance to the dTALE-containing Xoo strains. A dTALE gene was also generated to activate the recessive resistance gene xa13, an allele of the disease-susceptibility gene Os8N3 (also named Xa13 or OsSWEET11, a member of sucrose efflux transporter SWEET gene family). The induction of xa13 by the dTALE rendered the resistant rice IRBB13 (xa13/xa13) susceptible to Xoo. Finally, OsSWEET12, an as-yet uncharacterized SWEET gene with no corresponding naturally occurring TAL effector identified, conferred susceptibility to the Xoo strains expressing the corresponding dTALE genes. Our results demonstrate that dTALEs can be delivered through the bacterial secretion system to activate genes of interest for functional analysis in plants.

  5. Assembly of Customized TAL Effectors Through Advanced ULtiMATE System.

    PubMed

    Yang, Junjiao; Guo, Shengjie; Yuan, Pengfei; Wei, Wensheng

    2016-01-01

    Transcription activator-like effectors (TALEs) have been widely applied in gene targeting. Here we describe an advanced ULtiMATE (USER-based Ligation-Mediated Assembly of TAL Effector) system that utilizes USER fusion technique and archive of 512 tetramer templates to achieve highly efficient construction of TALEs, which takes only half a day to accomplish the assembly of any given TALE construct. This system is also suitable for large-scale assembly of TALENs and any other TALE-based constructions.

  6. An Improved Method for TAL Effectors DNA-Binding Sites Prediction Reveals Functional Convergence in TAL Repertoires of Xanthomonas oryzae Strains

    PubMed Central

    Pérez-Quintero, Alvaro L.; Rodriguez-R, Luis M.; Dereeper, Alexis; López, Camilo; Koebnik, Ralf; Szurek, Boris; Cunnac, Sebastien

    2013-01-01

    Transcription Activators-Like Effectors (TALEs) belong to a family of virulence proteins from the Xanthomonas genus of bacterial plant pathogens that are translocated into the plant cell. In the nucleus, TALEs act as transcription factors inducing the expression of susceptibility genes. A code for TALE-DNA binding specificity and high-resolution three-dimensional structures of TALE-DNA complexes were recently reported. Accurate prediction of TAL Effector Binding Elements (EBEs) is essential to elucidate the biological functions of the many sequenced TALEs as well as for robust design of artificial TALE DNA-binding domains in biotechnological applications. In this work a program with improved EBE prediction performances was developed using an updated specificity matrix and a position weight correction function to account for the matching pattern observed in a validation set of TALE-DNA interactions. To gain a systems perspective on the large TALE repertoires from X. oryzae strains, this program was used to predict rice gene targets for 99 sequenced family members. Integrating predictions and available expression data in a TALE-gene network revealed multiple candidate transcriptional targets for many TALEs as well as several possible instances of functional convergence among TALEs. PMID:23869221

  7. TALEs from a spring--superelasticity of Tal effector protein structures.

    PubMed

    Flechsig, Holger

    2014-01-01

    Transcription activator-like effectors (TALEs) are DNA-related proteins that recognise and bind specific target sequences to manipulate gene expression. Recently determined crystal structures show that their common architecture reveals a superhelical overall structure that may undergo drastic conformational changes. To establish a link between structure and dynamics in TALE proteins we have employed coarse-grained elastic-network modelling of currently available structural data and implemented a force-probe setup that allowed us to investigate their mechanical behaviour in computer experiments. Based on the measured force-extension curves we conclude that TALEs exhibit superelastic dynamical properties allowing for large-scale global conformational changes along their helical axis, which represents the soft direction in such proteins. For moderate external forcing the TALE models behave like linear springs, obeying Hooke's law, and the investigated structures can be characterised and compared by a corresponding spring constant. We show that conformational flexibility underlying the large-scale motions is not homogeneously distributed over the TALE structure, but instead soft spot residues around which strain is accumulated and which turn out to represent key agents in the transmission of conformational motions are identified. They correspond to the RVD loop residues that have been experimentally determined to play an eminent role in the binding process of target DNA.

  8. Molecular Dynamics Simulations of DNA-Free and DNA-Bound TAL Effectors

    PubMed Central

    Wan, Hua; Hu, Jian-ping; Li, Kang-shun; Tian, Xu-hong; Chang, Shan

    2013-01-01

    TAL (transcriptional activator-like) effectors (TALEs) are DNA-binding proteins, containing a modular central domain that recognizes specific DNA sequences. Recently, the crystallographic studies of TALEs revealed the structure of DNA-recognition domain. In this article, molecular dynamics (MD) simulations are employed to study two crystal structures of an 11.5-repeat TALE, in the presence and absence of DNA, respectively. The simulated results indicate that the specific binding of RVDs (repeat-variable diresidues) with DNA leads to the markedly reduced fluctuations of tandem repeats, especially at the two ends. In the DNA-bound TALE system, the base-specific interaction is formed mainly by the residue at position 13 within a TAL repeat. Tandem repeats with weak RVDs are unfavorable for the TALE-DNA binding. These observations are consistent with experimental studies. By using principal component analysis (PCA), the dominant motions are open-close movements between the two ends of the superhelical structure in both DNA-free and DNA-bound TALE systems. The open-close movements are found to be critical for the recognition and binding of TALE-DNA based on the analysis of free energy landscape (FEL). The conformational analysis of DNA indicates that the 5′ end of DNA target sequence has more remarkable structural deformability than the other sites. Meanwhile, the conformational change of DNA is likely associated with the specific interaction of TALE-DNA. We further suggest that the arrangement of N-terminal repeats with strong RVDs may help in the design of efficient TALEs. This study provides some new insights into the understanding of the TALE-DNA recognition mechanism. PMID:24130757

  9. TALEs from a Spring – Superelasticity of Tal Effector Protein Structures

    PubMed Central

    Flechsig, Holger

    2014-01-01

    Transcription activator-like effectors (TALEs) are DNA-related proteins that recognise and bind specific target sequences to manipulate gene expression. Recently determined crystal structures show that their common architecture reveals a superhelical overall structure that may undergo drastic conformational changes. To establish a link between structure and dynamics in TALE proteins we have employed coarse-grained elastic-network modelling of currently available structural data and implemented a force-probe setup that allowed us to investigate their mechanical behaviour in computer experiments. Based on the measured force-extension curves we conclude that TALEs exhibit superelastic dynamical properties allowing for large-scale global conformational changes along their helical axis, which represents the soft direction in such proteins. For moderate external forcing the TALE models behave like linear springs, obeying Hooke's law, and the investigated structures can be characterised and compared by a corresponding spring constant. We show that conformational flexibility underlying the large-scale motions is not homogeneously distributed over the TALE structure, but instead soft spot residues around which strain is accumulated and which turn out to represent key agents in the transmission of conformational motions are identified. They correspond to the RVD loop residues that have been experimentally determined to play an eminent role in the binding process of target DNA. PMID:25313859

  10. DNA-binding proteins from marine bacteria expand the known sequence diversity of TALE-like repeats

    PubMed Central

    de Lange, Orlando; Wolf, Christina; Thiel, Philipp; Krüger, Jens; Kleusch, Christian; Kohlbacher, Oliver; Lahaye, Thomas

    2015-01-01

    Transcription Activator-Like Effectors (TALEs) of Xanthomonas bacteria are programmable DNA binding proteins with unprecedented target specificity. Comparative studies into TALE repeat structure and function are hindered by the limited sequence variation among TALE repeats. More sequence-diverse TALE-like proteins are known from Ralstonia solanacearum (RipTALs) and Burkholderia rhizoxinica (Bats), but RipTAL and Bat repeats are conserved with those of TALEs around the DNA-binding residue. We study two novel marine-organism TALE-like proteins (MOrTL1 and MOrTL2), the first to date of non-terrestrial origin. We have assessed their DNA-binding properties and modelled repeat structures. We found that repeats from these proteins mediate sequence specific DNA binding conforming to the TALE code, despite low sequence similarity to TALE repeats, and with novel residues around the BSR. However, MOrTL1 repeats show greater sequence discriminating power than MOrTL2 repeats. Sequence alignments show that there are only three residues conserved between repeats of all TALE-like proteins including the two new additions. This conserved motif could prove useful as an identifier for future TALE-likes. Additionally, comparing MOrTL repeats with those of other TALE-likes suggests a common evolutionary origin for the TALEs, RipTALs and Bats. PMID:26481363

  11. DNA-binding proteins from marine bacteria expand the known sequence diversity of TALE-like repeats.

    PubMed

    de Lange, Orlando; Wolf, Christina; Thiel, Philipp; Krüger, Jens; Kleusch, Christian; Kohlbacher, Oliver; Lahaye, Thomas

    2015-11-16

    Transcription Activator-Like Effectors (TALEs) of Xanthomonas bacteria are programmable DNA binding proteins with unprecedented target specificity. Comparative studies into TALE repeat structure and function are hindered by the limited sequence variation among TALE repeats. More sequence-diverse TALE-like proteins are known from Ralstonia solanacearum (RipTALs) and Burkholderia rhizoxinica (Bats), but RipTAL and Bat repeats are conserved with those of TALEs around the DNA-binding residue. We study two novel marine-organism TALE-like proteins (MOrTL1 and MOrTL2), the first to date of non-terrestrial origin. We have assessed their DNA-binding properties and modelled repeat structures. We found that repeats from these proteins mediate sequence specific DNA binding conforming to the TALE code, despite low sequence similarity to TALE repeats, and with novel residues around the BSR. However, MOrTL1 repeats show greater sequence discriminating power than MOrTL2 repeats. Sequence alignments show that there are only three residues conserved between repeats of all TALE-like proteins including the two new additions. This conserved motif could prove useful as an identifier for future TALE-likes. Additionally, comparing MOrTL repeats with those of other TALE-likes suggests a common evolutionary origin for the TALEs, RipTALs and Bats. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Engineered TAL Effector modulators for the large-scale gain-of-function screening

    PubMed Central

    Zhang, Hanshuo; Li, Juan; Hou, Sha; Wang, Gancheng; Jiang, Mingjun; Sun, Changhong; Hu, Xiongbing; Zhuang, Fengfeng; Dai, Zhifei; Dai, Junbiao; Xi, Jianzhong Jeff

    2014-01-01

    Recent effective use of TAL Effectors (TALEs) has provided an important approach to the design and synthesis of sequence-specific DNA-binding proteins. However, it is still a challenging task to design and manufacture effective TALE modulators because of the limited knowledge of TALE–DNA interactions. Here we synthesized more than 200 TALE modulators and identified two determining factors of transcription activity in vivo: chromatin accessibility and the distance from the transcription start site. The implementation of these modulators in a gain-of-function screen was successfully demonstrated for four cell lines in migration/invasion assays and thus has broad relevance in this field. Furthermore, a novel TALE–TALE modulator was developed to transcriptionally inhibit target genes. Together, these findings underscore the huge potential of these TALE modulators in the study of gene function, reprogramming of cellular behaviors, and even clinical investigation. PMID:24939900

  13. A TALE-inspired computational screen for proteins that contain approximate tandem repeats.

    PubMed

    Perycz, Malgorzata; Krwawicz, Joanna; Bochtler, Matthias

    2017-01-01

    TAL (transcription activator-like) effectors (TALEs) are bacterial proteins that are secreted from bacteria to plant cells to act as transcriptional activators. TALEs and related proteins (RipTALs, BurrH, MOrTL1 and MOrTL2) contain approximate tandem repeats that differ in conserved positions that define specificity. Using PERL, we screened ~47 million protein sequences for TALE-like architecture characterized by approximate tandem repeats (between 30 and 43 amino acids in length) and sequence variability in conserved positions, without requiring sequence similarity to TALEs. Candidate proteins were scored according to their propensity for nuclear localization, secondary structure, repeat sequence complexity, as well as covariation and predicted structural proximity of variable residues. Biological context was tentatively inferred from co-occurrence of other domains and interactome predictions. Approximate repeats with TALE-like features that merit experimental characterization were found in a protein of chestnut blight fungus, a eukaryotic plant pathogen.

  14. A TALE-inspired computational screen for proteins that contain approximate tandem repeats

    PubMed Central

    Krwawicz, Joanna

    2017-01-01

    TAL (transcription activator-like) effectors (TALEs) are bacterial proteins that are secreted from bacteria to plant cells to act as transcriptional activators. TALEs and related proteins (RipTALs, BurrH, MOrTL1 and MOrTL2) contain approximate tandem repeats that differ in conserved positions that define specificity. Using PERL, we screened ~47 million protein sequences for TALE-like architecture characterized by approximate tandem repeats (between 30 and 43 amino acids in length) and sequence variability in conserved positions, without requiring sequence similarity to TALEs. Candidate proteins were scored according to their propensity for nuclear localization, secondary structure, repeat sequence complexity, as well as covariation and predicted structural proximity of variable residues. Biological context was tentatively inferred from co-occurrence of other domains and interactome predictions. Approximate repeats with TALE-like features that merit experimental characterization were found in a protein of chestnut blight fungus, a eukaryotic plant pathogen. PMID:28617832

  15. Breaking the DNA-binding code of Ralstonia solanacearum TAL effectors provides new possibilities to generate plant resistance genes against bacterial wilt disease.

    PubMed

    de Lange, Orlando; Schreiber, Tom; Schandry, Niklas; Radeck, Jara; Braun, Karl Heinz; Koszinowski, Julia; Heuer, Holger; Strauß, Annett; Lahaye, Thomas

    2013-08-01

    Ralstonia solanacearum is a devastating bacterial phytopathogen with a broad host range. Ralstonia solanacearum injected effector proteins (Rips) are key to the successful invasion of host plants. We have characterized Brg11(hrpB-regulated 11), the first identified member of a class of Rips with high sequence similarity to the transcription activator-like (TAL) effectors of Xanthomonas spp., collectively termed RipTALs. Fluorescence microscopy of in planta expressed RipTALs showed nuclear localization. Domain swaps between Brg11 and Xanthomonas TAL effector (TALE) AvrBs3 (avirulence protein triggering Bs3 resistance) showed the functional interchangeability of DNA-binding and transcriptional activation domains. PCR was used to determine the sequence of brg11 homologs from strains infecting phylogenetically diverse host plants. Brg11 localizes to the nucleus and activates promoters containing a matching effector-binding element (EBE). Brg11 and homologs preferentially activate promoters containing EBEs with a 5' terminal guanine, contrasting with the TALE preference for a 5' thymine. Brg11 and other RipTALs probably promote disease through the transcriptional activation of host genes. Brg11 and the majority of homologs identified in this study were shown to activate similar or identical target sequences, in contrast to TALEs, which generally show highly diverse target preferences. This information provides new options for the engineering of plants resistant to R. solanacearum. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  16. Direct regulation of E-cadherin by targeted histone methylation of TALE-SET fusion protein in cancer cells.

    PubMed

    Cho, Hyun-Soo; Kang, Jeong Gu; Lee, Jae-Hye; Lee, Jeong-Ju; Jeon, Seong Kook; Ko, Jeong-Heon; Kim, Dae-Soo; Park, Kun-Hyang; Kim, Yong-Sam; Kim, Nam-Soon

    2015-09-15

    TALE-nuclease chimeras (TALENs) can bind to and cleave specific genomic loci and, are used to engineer gene knockouts and additions. Recently, instead of using the FokI domain, epigenetically active domains, such as TET1 and LSD1, have been combined with TAL effector domains to regulate targeted gene expression via DNA and histone demethylation. However, studies of histone methylation in the TALE system have not been performed. Therefore, in this study, we established a novel targeted regulation system with a TAL effector domain and a histone methylation domain. To construct a TALE-methylation fusion protein, we combined a TAL effector domain containing an E-Box region to act as a Snail binding site and the SET domain of EHMT 2 to allow for histone methylation. The constructed TALE-SET module (TSET) repressed the expression of E-cadherin via by increasing H3K9 dimethylation. Moreover, the cells that overexpressed TSET showed increased cell migration and invasion. This is the first phenotype-based study of targeted histone methylation by the TALE module, and this new system can be applied in new cancer therapies to reduce side effects.

  17. Computational Predictions Provide Insights into the Biology of TAL Effector Target Sites

    PubMed Central

    Grau, Jan; Wolf, Annett; Reschke, Maik; Bonas, Ulla; Posch, Stefan; Boch, Jens

    2013-01-01

    Transcription activator-like (TAL) effectors are injected into host plant cells by Xanthomonas bacteria to function as transcriptional activators for the benefit of the pathogen. The DNA binding domain of TAL effectors is composed of conserved amino acid repeat structures containing repeat-variable diresidues (RVDs) that determine DNA binding specificity. In this paper, we present TALgetter, a new approach for predicting TAL effector target sites based on a statistical model. In contrast to previous approaches, the parameters of TALgetter are estimated from training data computationally. We demonstrate that TALgetter successfully predicts known TAL effector target sites and often yields a greater number of predictions that are consistent with up-regulation in gene expression microarrays than an existing approach, Target Finder of the TALE-NT suite. We study the binding specificities estimated by TALgetter and approve that different RVDs are differently important for transcriptional activation. In subsequent studies, the predictions of TALgetter indicate a previously unreported positional preference of TAL effector target sites relative to the transcription start site. In addition, several TAL effectors are predicted to bind to the TATA-box, which might constitute one general mode of transcriptional activation by TAL effectors. Scrutinizing the predicted target sites of TALgetter, we propose several novel TAL effector virulence targets in rice and sweet orange. TAL-mediated induction of the candidates is supported by gene expression microarrays. Validity of these targets is also supported by functional analogy to known TAL effector targets, by an over-representation of TAL effector targets with similar function, or by a biological function related to pathogen infection. Hence, these predicted TAL effector virulence targets are promising candidates for studying the virulence function of TAL effectors. TALgetter is implemented as part of the open-source Java library

  18. Context influences on TALE-DNA binding revealed by quantitative profiling.

    PubMed

    Rogers, Julia M; Barrera, Luis A; Reyon, Deepak; Sander, Jeffry D; Kellis, Manolis; Joung, J Keith; Bulyk, Martha L

    2015-06-11

    Transcription activator-like effector (TALE) proteins recognize DNA using a seemingly simple DNA-binding code, which makes them attractive for use in genome engineering technologies that require precise targeting. Although this code is used successfully to design TALEs to target specific sequences, off-target binding has been observed and is difficult to predict. Here we explore TALE-DNA interactions comprehensively by quantitatively assaying the DNA-binding specificities of 21 representative TALEs to ∼5,000-20,000 unique DNA sequences per protein using custom-designed protein-binding microarrays (PBMs). We find that protein context features exert significant influences on binding. Thus, the canonical recognition code does not fully capture the complexity of TALE-DNA binding. We used the PBM data to develop a computational model, Specificity Inference For TAL-Effector Design (SIFTED), to predict the DNA-binding specificity of any TALE. We provide SIFTED as a publicly available web tool that predicts potential genomic off-target sites for improved TALE design.

  19. TAL effector-DNA specificity.

    PubMed

    Scholze, Heidi; Boch, Jens

    2010-01-01

    TAL effectors are important virulence factors of bacterial plant pathogenic Xanthomonas, which infect a wide variety of plants including valuable crops like pepper, rice, and citrus. TAL proteins are translocated via the bacterial type III secretion system into host cells and induce transcription of plant genes by binding to target gene promoters. Members of the TAL effector family differ mainly in their central domain of tandemly arranged repeats of typically 34 amino acids each with hypervariable di-amino acids at positions 12 and 13. We recently showed that target DNA-recognition specificity of TAL effectors is encoded in a modular and clearly predictable mode. The repeats of TAL effectors feature a surprising one repeat-to-one-bp correlation with different repeat types exhibiting a different DNA base pair specificity. Accordingly, we predicted DNA specificities of TAL effectors and generated artificial TAL proteins with novel DNA recognition specificities. We describe here novel artificial TALs and discuss implications for the DNA recognition specificity. The unique TAL-DNA binding domain allows design of proteins with potentially any given DNA recognition specificity enabling many uses for biotechnology.

  20. QueTAL: a suite of tools to classify and compare TAL effectors functionally and phylogenetically

    PubMed Central

    Pérez-Quintero, Alvaro L.; Lamy, Léo; Gordon, Jonathan L.; Escalon, Aline; Cunnac, Sébastien; Szurek, Boris; Gagnevin, Lionel

    2015-01-01

    Transcription Activator-Like (TAL) effectors from Xanthomonas plant pathogenic bacteria can bind to the promoter region of plant genes and induce their expression. DNA-binding specificity is governed by a central domain made of nearly identical repeats, each determining the recognition of one base pair via two amino acid residues (a.k.a. Repeat Variable Di-residue, or RVD). Knowing how TAL effectors differ from each other within and between strains would be useful to infer functional and evolutionary relationships, but their repetitive nature precludes reliable use of traditional alignment methods. The suite QueTAL was therefore developed to offer tailored tools for comparison of TAL effector genes. The program DisTAL considers each repeat as a unit, transforms a TAL effector sequence into a sequence of coded repeats and makes pair-wise alignments between these coded sequences to construct trees. The program FuncTAL is aimed at finding TAL effectors with similar DNA-binding capabilities. It calculates correlations between position weight matrices of potential target DNA sequence predicted from the RVD sequence, and builds trees based on these correlations. The programs accurately represented phylogenetic and functional relationships between TAL effectors using either simulated or literature-curated data. When using the programs on a large set of TAL effector sequences, the DisTAL tree largely reflected the expected species phylogeny. In contrast, FuncTAL showed that TAL effectors with similar binding capabilities can be found between phylogenetically distant taxa. This suite will help users to rapidly analyse any TAL effector genes of interest and compare them to other available TAL genes and should improve our understanding of TAL effectors evolution. It is available at http://bioinfo-web.mpl.ird.fr/cgi-bin2/quetal/quetal.cgi. PMID:26284082

  1. TALE-Like Effectors Are an Ancestral Feature of the Ralstonia solanacearum Species Complex and Converge in DNA Targeting Specificity.

    PubMed

    Schandry, Niklas; de Lange, Orlando; Prior, Philippe; Lahaye, Thomas

    2016-01-01

    Ralstonia solanacearum, a species complex of bacterial plant pathogens divided into four monophyletic phylotypes, causes plant diseases in tropical climates around the world. Some strains exhibit a broad host range on solanaceous hosts, while others are highly host-specific as for example some banana-pathogenic strains. Previous studies showed that transcription activator-like (TAL) effectors from Ralstonia, termed RipTALs, are capable of activating reporter genes in planta, if these are preceded by a matching effector binding element (EBE). RipTALs target DNA via their central repeat domain (CRD), where one repeat pairs with one DNA-base of the given EBE. The repeat variable diresidue dictates base repeat specificity in a predictable fashion, known as the TALE code. In this work, we analyze RipTALs across all phylotypes of the Ralstonia solanacearum species complex. We find that RipTALs are prevalent in phylotypes I and IV but absent from most phylotype III and II strains (10/12, 8/14, 1/24, and 1/5 strains contained a RipTAL, respectively). RipTALs originating from strains of the same phylotype show high levels of sequence similarity (>98%) in the N-terminal and C-terminal regions, while RipTALs isolated from different phylotypes show 47-91% sequence similarity in those regions, giving rise to four RipTAL classes. We show that, despite sequence divergence, the base preference for guanine, mediated by the N-terminal region, is conserved across RipTALs of all classes. Using the number and order of repeats found in the CRD, we functionally sub-classify RipTALs, introduce a new simple nomenclature, and predict matching EBEs for all seven distinct RipTALs identified. We experimentally study RipTAL EBEs and uncover that some RipTALs are able to target the EBEs of other RipTALs, referred to as cross-reactivity. In particular, RipTALs from strains with a broad host range on solanaceous hosts cross-react on each other's EBEs. Investigation of sequence divergence between

  2. A multicolor panel of TALE-KRAB based transcriptional repressor vectors enabling knockdown of multiple gene targets

    PubMed Central

    Zhang, Zhonghui; Wu, Elise; Qian, Zhijian; Wu, Wen-Shu

    2014-01-01

    Stable and efficient knockdown of multiple gene targets is highly desirable for dissection of molecular pathways. Because it allows sequence-specific DNA binding, transcription activator-like effector (TALE) offers a new genetic perturbation technique that allows for gene-specific repression. Here, we constructed a multicolor lentiviral TALE-Kruppel-associated box (KRAB) expression vector platform that enables knockdown of multiple gene targets. This platform is fully compatible with the Golden Gate TALEN and TAL Effector Kit 2.0, a widely used and efficient method for TALE assembly. We showed that this multicolor TALE-KRAB vector system when combined together with bone marrow transplantation could quickly knock down c-kit and PU.1 genes in hematopoietic stem and progenitor cells of recipient mice. Furthermore, our data demonstrated that this platform simultaneously knocked down both c-Kit and PU.1 genes in the same primary cell populations. Together, our results suggest that this multicolor TALE-KRAB vector platform is a promising and versatile tool for knockdown of multiple gene targets and could greatly facilitate dissection of molecular pathways. PMID:25475013

  3. A multicolor panel of TALE-KRAB based transcriptional repressor vectors enabling knockdown of multiple gene targets.

    PubMed

    Zhang, Zhonghui; Wu, Elise; Qian, Zhijian; Wu, Wen-Shu

    2014-12-05

    Stable and efficient knockdown of multiple gene targets is highly desirable for dissection of molecular pathways. Because it allows sequence-specific DNA binding, transcription activator-like effector (TALE) offers a new genetic perturbation technique that allows for gene-specific repression. Here, we constructed a multicolor lentiviral TALE-Kruppel-associated box (KRAB) expression vector platform that enables knockdown of multiple gene targets. This platform is fully compatible with the Golden Gate TALEN and TAL Effector Kit 2.0, a widely used and efficient method for TALE assembly. We showed that this multicolor TALE-KRAB vector system when combined together with bone marrow transplantation could quickly knock down c-kit and PU.1 genes in hematopoietic stem and progenitor cells of recipient mice. Furthermore, our data demonstrated that this platform simultaneously knocked down both c-Kit and PU.1 genes in the same primary cell populations. Together, our results suggest that this multicolor TALE-KRAB vector platform is a promising and versatile tool for knockdown of multiple gene targets and could greatly facilitate dissection of molecular pathways.

  4. TALE: a tale of genome editing.

    PubMed

    Zhang, Mingjie; Wang, Feng; Li, Shifei; Wang, Yan; Bai, Yun; Xu, Xueqing

    2014-01-01

    Transcription activator-like effectors (TALEs), first identified in Xanthomonas bacteria, are naturally occurring or artificially designed proteins that modulate gene transcription. These proteins recognize and bind DNA sequences based on a variable numbers of tandem repeats. Each repeat is comprised of a set of ∼ 34 conserved amino acids; within this conserved domain, there are usually two amino acids that distinguish one TALE from another. Interestingly, TALEs have revealed a simple cipher for the one-to-one recognition of proteins for DNA bases. Synthetic TALEs have been used to successfully target genes in a variety of species, including humans. Depending on the type of functional domain that is fused to the TALE of interest, these proteins can have diverse biological effects. For example, after binding DNA, TALEs fused to transcriptional activation domains can function as robust transcription factors (TALE-TFs), while fused to restriction endonucleases (TALENs) can cut DNA. Targeted genome editing, in theory, is capable of modifying any endogenous gene sequence of interest; this can be performed in cells or organisms, and may be applied to clinical gene-based therapies in the future. With current technologies, highly accurate, specific, and reliable gene editing cannot be achieved. Thus, recognition and binding mechanisms governing TALE biology are currently hot research areas. In this review, we summarize the major advances in TALE technology over the past several years with a focus on the interaction between TALEs and DNA, TALE design and construction, potential applications for this technology, and unique characteristics that make TALEs superior to zinc finger endonucleases. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. MorTAL Kombat: the story of defense against TAL effectors through loss-of-susceptibility

    PubMed Central

    Hutin, Mathilde; Pérez-Quintero, Alvaro L.; Lopez, Camilo; Szurek, Boris

    2015-01-01

    Many plant-pathogenic xanthomonads rely on Transcription Activator-Like (TAL) effectors to colonize their host. This particular family of type III effectors functions as specific plant transcription factors via a programmable DNA-binding domain. Upon binding to the promoters of plant disease susceptibility genes in a sequence-specific manner, the expression of these host genes is induced. However, plants have evolved specific strategies to counter the action of TAL effectors and confer resistance. One mechanism is to avoid the binding of TAL effectors by mutations of their DNA binding sites, resulting in resistance by loss-of-susceptibility. This article reviews our current knowledge of the susceptibility hubs targeted by Xanthomonas TAL effectors, possible evolutionary scenarios for plants to combat the pathogen with loss-of-function alleles, and how this knowledge can be used overall to develop new pathogen-informed breeding strategies and improve crop resistance. PMID:26236326

  6. Engineering synthetic TAL effectors with orthogonal target sites

    PubMed Central

    Garg, Abhishek; Lohmueller, Jason J.; Silver, Pamela A.; Armel, Thomas Z.

    2012-01-01

    The ability to engineer biological circuits that process and respond to complex cellular signals has the potential to impact many areas of biology and medicine. Transcriptional activator-like effectors (TALEs) have emerged as an attractive component for engineering these circuits, as TALEs can be designed de novo to target a given DNA sequence. Currently, however, the use of TALEs is limited by degeneracy in the site-specific manner by which they recognize DNA. Here, we propose an algorithm to computationally address this problem. We apply our algorithm to design 180 TALEs targeting 20 bp cognate binding sites that are at least 3 nt mismatches away from all 20 bp sequences in putative 2 kb human promoter regions. We generated eight of these synthetic TALE activators and showed that each is able to activate transcription from a targeted reporter. Importantly, we show that these proteins do not activate synthetic reporters containing mismatches similar to those present in the genome nor a set of endogenous genes predicted to be the most likely targets in vivo. Finally, we generated and characterized TALE repressors comprised of our orthogonal DNA binding domains and further combined them with shRNAs to accomplish near complete repression of target gene expression. PMID:22581776

  7. AnnoTALE: bioinformatics tools for identification, annotation, and nomenclature of TALEs from Xanthomonas genomic sequences

    PubMed Central

    Grau, Jan; Reschke, Maik; Erkes, Annett; Streubel, Jana; Morgan, Richard D.; Wilson, Geoffrey G.; Koebnik, Ralf; Boch, Jens

    2016-01-01

    Transcription activator-like effectors (TALEs) are virulence factors, produced by the bacterial plant-pathogen Xanthomonas, that function as gene activators inside plant cells. Although the contribution of individual TALEs to infectivity has been shown, the specific roles of most TALEs, and the overall TALE diversity in Xanthomonas spp. is not known. TALEs possess a highly repetitive DNA-binding domain, which is notoriously difficult to sequence. Here, we describe an improved method for characterizing TALE genes by the use of PacBio sequencing. We present ‘AnnoTALE’, a suite of applications for the analysis and annotation of TALE genes from Xanthomonas genomes, and for grouping similar TALEs into classes. Based on these classes, we propose a unified nomenclature for Xanthomonas TALEs that reveals similarities pointing to related functionalities. This new classification enables us to compare related TALEs and to identify base substitutions responsible for the evolution of TALE specificities. PMID:26876161

  8. TAL effectors and the executor R genes

    PubMed Central

    Zhang, Junli; Yin, Zhongchao; White, Frank

    2015-01-01

    Transcription activator-like (TAL) effectors are bacterial type III secretion proteins that function as transcription factors in plants during Xanthomonas/plant interactions, conditioning either host susceptibility and/or host resistance. Three types of TAL effector associated resistance (R) genes have been characterized—recessive, dominant non-transcriptional, and dominant TAL effector-dependent transcriptional based resistance. Here, we discuss the last type of R genes, whose functions are dependent on direct TAL effector binding to discrete effector binding elements in the promoters. Only five of the so-called executor R genes have been cloned, and commonalities are not clear. We have placed the protein products in two groups for conceptual purposes. Group 1 consists solely of the protein from pepper, BS3, which is predicted to have catalytic function on the basis of homology to a large conserved protein family. Group 2 consists of BS4C-R, XA27, XA10, and XA23, all of which are relatively short proteins from pepper or rice with multiple potential transmembrane domains. Group 2 members have low sequence similarity to proteins of unknown function in closely related species. Firm predictions await further experimentation on these interesting new members to the R gene repertoire, which have potential broad application in new strategies for disease resistance. PMID:26347759

  9. TAL effectors and the executor R genes.

    PubMed

    Zhang, Junli; Yin, Zhongchao; White, Frank

    2015-01-01

    Transcription activator-like (TAL) effectors are bacterial type III secretion proteins that function as transcription factors in plants during Xanthomonas/plant interactions, conditioning either host susceptibility and/or host resistance. Three types of TAL effector associated resistance (R) genes have been characterized-recessive, dominant non-transcriptional, and dominant TAL effector-dependent transcriptional based resistance. Here, we discuss the last type of R genes, whose functions are dependent on direct TAL effector binding to discrete effector binding elements in the promoters. Only five of the so-called executor R genes have been cloned, and commonalities are not clear. We have placed the protein products in two groups for conceptual purposes. Group 1 consists solely of the protein from pepper, BS3, which is predicted to have catalytic function on the basis of homology to a large conserved protein family. Group 2 consists of BS4C-R, XA27, XA10, and XA23, all of which are relatively short proteins from pepper or rice with multiple potential transmembrane domains. Group 2 members have low sequence similarity to proteins of unknown function in closely related species. Firm predictions await further experimentation on these interesting new members to the R gene repertoire, which have potential broad application in new strategies for disease resistance.

  10. [Tale nucleases--new tool for genome editing].

    PubMed

    Glazkova, D V; Shipulin, G A

    2014-01-01

    The ability to introduce targeted changes in the genome of living cells or entire organisms enables researchers to meet the challenges of basic life sciences, biotechnology and medicine. Knockdown of target genes in the zygotes gives the opportunity to investigate the functions of these genes in different organisms. Replacement of single nucleotide in the DNA sequence allows to correct mutations in genes and thus to cure hereditary diseases. Adding transgene to specific genomic.loci can be used in biotechnology for generation of organisms with certain properties or cell lines for biopharmaceutical production. Such manipulations of gene sequences in their natural chromosomal context became possible after the emergence of the technology called "genome editing". This technology is based on the induction of a double-strand break in a specific genomic target DNA using endonucleases that recognize the unique sequences in the genome and on subsequent recovery of DNA integrity through the use of cellular repair mechanisms. A necessary tool for the genome editing is a custom-designed endonuclease which is able to recognize selected sequences. The emergence of a new type of programmable endonucleases, which were constructed on the basis of bacterial proteins--TAL-effectors (Transcription activators like effector), has become an important stage in the development of technology and promoted wide spread of the genome editing. This article reviews the history of the discovery of TAL effectors and creation of TALE nucleases, and describes their advantages over zinc finger endonucleases that appeared earlier. A large section is devoted to description of genetic modifications that can be performed using the genome editing.

  11. Lost Opportunities: Rediscovering Fairy Tales

    ERIC Educational Resources Information Center

    Wipf, Joan Brogan; Da Ros-Voseles, Denise

    2012-01-01

    The power of fairy tales resonates with children around the world. Fairy tales connect children on an emotional level that can help guide them through the complexities of everyday life. The tales provide stories rich in cultural heritage and the human condition, stories that not only delight children but also instruct. Because fairy tales state…

  12. Richard Halliburton's Bearded Tales

    ERIC Educational Resources Information Center

    Morris, Charles E., III

    2009-01-01

    Fusing the concept of "the beard" with the genre of the tall tale to theorize bearded tales deepens our understanding of closet eloquence, or rhetorical repertories of sexual passing in U.S. history. An examination of adventurer-writer-lecturer Richard Halliburton's sexual provenance and bestselling travel tale, "The Royal Road to Romance" (1925),…

  13. Fairy Tales from Life.

    ERIC Educational Resources Information Center

    Schulze, Patricia

    With the help of the teacher, students will read fairy tales and identify common elements. Choosing common situations and working in small groups, students will draw storyboards of their fairy tale and then write the fairy tale. Project will conclude with class presentations. During ten 50-minute lessons, grade 3-5 students will: listen and read…

  14. Transcription activator-like (TAL) effectors targeting OsSWEET genes enhance virulence on diverse rice (Oryza sativa) varieties when expressed individually in a TAL effector-deficient strain of Xanthomonas oryzae.

    PubMed

    Verdier, Valérie; Triplett, Lindsay R; Hummel, Aaron W; Corral, Rene; Cernadas, R Andres; Schmidt, Clarice L; Bogdanove, Adam J; Leach, Jan E

    2012-12-01

    Genomes of the rice (Oryza sativa) xylem and mesophyll pathogens Xanthomonas oryzae pv. oryzae (Xoo) and pv. oryzicola (Xoc) encode numerous secreted transcription factors called transcription activator-like (TAL) effectors. In a few studied rice varieties, some of these contribute to virulence by activating corresponding host susceptibility genes. Some activate disease resistance genes. The roles of X. oryzae TAL effectors in diverse rice backgrounds, however, are poorly understood. Xoo TAL effectors that promote infection by activating SWEET sucrose transporter genes were expressed in TAL effector-deficient X. oryzae strain X11-5A, and assessed in 21 rice varieties. Some were also tested in Xoc on variety Nipponbare. Several Xoc TAL effectors were tested in X11-5A on four rice varieties. Xoo TAL effectors enhanced X11-5A virulence on most varieties, but to varying extents depending on the effector and variety. SWEET genes were activated in all tested varieties, but increased virulence did not correlate with activation level. SWEET activators also enhanced Xoc virulence on Nipponbare. Xoc TAL effectors did not alter X11-5A virulence. SWEET-targeting TAL effectors contribute broadly and non-tissue-specifically to virulence in rice, and their function is affected by host differences besides target sequences. Further, the utility of X11-5A for characterizing individual TAL effectors in rice was established. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  15. The last half-repeat of transcription activator-like effector (TALE) is dispensable and thereby TALE-based technology can be simplified.

    PubMed

    Zheng, Chong-Ke; Wang, Chun-Lian; Zhang, Xiao-Ping; Wang, Fu-Jun; Qin, Teng-Fei; Zhao, Kai-Jun

    2014-09-01

    To activate the expression of host genes that contribute to pathogen growth, pathogenic Xanthomonas bacteria inject their transcription activator-like effectors (TALEs) into plant cells and the TALEs bind to target gene promoters by the central repeat region consisting of near-perfect 34-amino-acid repeats (34-aa repeats). Based on the recognition codes between the 34-aa repeats and the targeted nucleotides, TALE-based technologies, such as designer TALEs (dTALEs) and TALE nucleases (TALENs), have been developed. Amazingly, every natural TALE invariantly has a truncated last half-repeat (LHR) at the end of the 34-aa repeats. Consequently, all the reported dTALEs and TALENs also harbour their LHRs. Here, we show that the LHRs in dTALEs are dispensable for the function of gene activation by both transient expression assays in Nicotiana benthamiana and gene-specific targeting in the rice genome, indicating that TALEs might originate from a single progenitor. In the light of this finding, we demonstrate that dTALEs can be constructed through two simple steps. Moreover, the activation strengths of dTALEs lacking the LHR are comparable with those of dTALEs harbouring the LHR. Our results provide new insights into the origin of natural TALEs, and will facilitate the simplification of the design and assembly of TALE-based tools, such as dTALEs and TALENs, in the near future. © 2014 BSPP AND JOHN WILEY & SONS LTD.

  16. American Hyperbole: The Tall Tale.

    ERIC Educational Resources Information Center

    Pavonetti, Linda M.; Combs, Christine M.

    1999-01-01

    Discusses the historic derivation and the format and characteristics of traditional tall tales, and modern adaptations of these stories. Describes a selection of tall tales for modern young adult readers; notes titles and authors of original tall tales and those with female heroes. Discusses the enduring appeal of traditional and modern tall…

  17. Twisters, Tall Tales, & Science Teaching

    ERIC Educational Resources Information Center

    Wilcox, Dawn Renee; Sterling, Donna R.

    2006-01-01

    Legends and tall tales have been part of the American culture for ages. Students are probably already familiar with the tales of how Pecos Bill fearlessly tamed a ferocious tornado, or Paul Bunyan effortlessly restrained a great river. Such tales have been passed down from generation to generation to explain humanity, the natural world, and…

  18. Chromatin looping defines expression of TAL1, its flanking genes, and regulation in T-ALL.

    PubMed

    Zhou, Yan; Kurukuti, Sreenivasulu; Saffrey, Peter; Vukovic, Milica; Michie, Alison M; Strogantsev, Ruslan; West, Adam G; Vetrie, David

    2013-12-19

    TAL1 is an important regulator of hematopoiesis and its expression is tightly controlled despite complexities in its genomic organization. It is frequently misregulated in T-cell acute lymphoblastic leukemia (T-ALL), often due to deletions between TAL1 and the neighboring STIL gene. To better understand the events that lead to TAL1 expression in hematopoiesis and in T-ALL, we studied looping interactions at the TAL1 locus. In TAL1-expressing erythroid cells, the locus adopts a looping "hub" which brings into close physical proximity all known TAL1 cis-regulatory elements including CTCF-bound insulators. Loss of GATA1 results in disassembly of the hub and loss of CTCF/RAD21 from one of its insulators. Genes flanking TAL1 are partly dependent on hub integrity for their transcriptional regulation. We identified looping patterns unique to TAL1-expressing T-ALL cells, and, intriguingly, loops occurring between the TAL1 and STIL genes at the common TAL1/STIL breakpoints found in T-ALL. These findings redefine how TAL1 and neighboring genes communicate within the nucleus, and indicate that looping facilitates both normal and aberrant TAL1 expression and may predispose to structural rearrangements in T-ALL. We also propose that GATA1-dependent looping mechanisms may facilitate the conservation of TAL1 regulation despite cis-regulatory remodeling during vertebrate evolution.

  19. Xanthomonas adaptation to common bean is associated with horizontal transfers of genes encoding TAL effectors.

    PubMed

    Ruh, Mylène; Briand, Martial; Bonneau, Sophie; Jacques, Marie-Agnès; Chen, Nicolas W G

    2017-08-30

    Common bacterial blight is a devastating bacterial disease of common bean (Phaseolus vulgaris) caused by Xanthomonas citri pv. fuscans and Xanthomonas phaseoli pv. phaseoli. These phylogenetically distant strains are able to cause similar symptoms on common bean, suggesting that they have acquired common genetic determinants of adaptation to common bean. Transcription Activator-Like (TAL) effectors are bacterial type III effectors that are able to induce the expression of host genes to promote infection or resistance. Their capacity to bind to a specific host DNA sequence suggests that they are potential candidates for host adaption. To study the diversity of tal genes from Xanthomonas strains responsible for common bacterial blight of bean, whole genome sequences of 17 strains representing the diversity of X. citri pv. fuscans and X. phaseoli pv. phaseoli were obtained by single molecule real time sequencing. Analysis of these genomes revealed the existence of four tal genes named tal23A, tal20F, tal18G and tal18H, respectively. While tal20F and tal18G were chromosomic, tal23A and tal18H were carried on plasmids and shared between phylogenetically distant strains, therefore suggesting recent horizontal transfers of these genes between X. citri pv. fuscans and X. phaseoli pv. phaseoli strains. Strikingly, tal23A was present in all strains studied, suggesting that it played an important role in adaptation to common bean. In silico predictions of TAL effectors targets in the common bean genome suggested that TAL effectors shared by X. citri pv. fuscans and X. phaseoli pv. phaseoli strains target the promoters of genes of similar functions. This could be a trace of convergent evolution among TAL effectors from different phylogenetic groups, and comforts the hypothesis that TAL effectors have been implied in the adaptation to common bean. Altogether, our results favour a model where plasmidic TAL effectors are able to contribute to host adaptation by being horizontally

  20. Activation of silenced cytokine gene promoters by the synergistic effect of TBP-TALE and VP64-TALE activators.

    PubMed

    Anthony, Kim; More, Abhijit; Zhang, Xiaoliu

    2014-01-01

    Recent work has shown that the combinatorial use of multiple TALE activators can selectively activate certain cellular genes in inaccessible chromatin regions. In this study, we aimed to interrogate the activation potential of TALEs upon transcriptionally silenced immune genes in the context of non-immune cells. We designed a unique strategy, in which a single TALE fused to the TATA-box binding protein (TBP-TALE) is coupled with multiple VP64-TALE activators. We found that our strategy is significantly more potent than multiple TALE activators alone in activating expression of IL-2 and GM-CSF in diverse cell origins in which both genes are otherwise completely silenced. Chromatin analysis revealed that the gene activation was due in part to displacement of a distinctly positioned nucleosome. These studies provide a novel epigenetic mechanism for artificial gene induction and have important implications for targeted cancer immunotherapy, DNA vaccine development, as well as rational design of TALE activators.

  1. Activation of Silenced Cytokine Gene Promoters by the Synergistic Effect of TBP-TALE and VP64-TALE Activators

    PubMed Central

    Anthony, Kim; More, Abhijit; Zhang, Xiaoliu

    2014-01-01

    Recent work has shown that the combinatorial use of multiple TALE activators can selectively activate certain cellular genes in inaccessible chromatin regions. In this study, we aimed to interrogate the activation potential of TALEs upon transcriptionally silenced immune genes in the context of non-immune cells. We designed a unique strategy, in which a single TALE fused to the TATA-box binding protein (TBP-TALE) is coupled with multiple VP64-TALE activators. We found that our strategy is significantly more potent than multiple TALE activators alone in activating expression of IL-2 and GM-CSF in diverse cell origins in which both genes are otherwise completely silenced. Chromatin analysis revealed that the gene activation was due in part to displacement of a distinctly positioned nucleosome. These studies provide a novel epigenetic mechanism for artificial gene induction and have important implications for targeted cancer immunotherapy, DNA vaccine development, as well as rational design of TALE activators. PMID:24755922

  2. Deconstructing Gender in Revised Feminist Fairy Tales

    ERIC Educational Resources Information Center

    Mcandrew, Linda

    2013-01-01

    Power relationships are a central premise in children's literature, especially traditional fairy tales and modern feminist fairy tales. This is seen in many fairy tales where the main female character is in some distress, her Prince Charming rescues her, and they live happily ever after. Modern feminist fairy tales are understood to be a forum…

  3. HANSEL AND GRETEL: A TALE OF TERROR.

    PubMed

    White, Robert S

    2015-10-01

    In the analysis of a woman with multiple childhood traumas, the fairy tale "Hansel and Gretel" figured prominently. The author discusses the use of the fairy tale in this case at various levels. He suggests an interplay between a national myth, the fairy tale, and a personal myth-the patient's psychodynamics. The fairy tale can be used to illuminate personal meanings derived from it. In the experience of childhood trauma, the repeated reading of a fairy tale can help organize and defend against terrifying anxiety. © 2015 The Psychoanalytic Quarterly, Inc.

  4. Engineering customized TALE nucleases (TALENs) and TALE transcription factors by fast ligation-based automatable solid-phase high-throughput (FLASH) assembly.

    PubMed

    Reyon, Deepak; Maeder, Morgan L; Khayter, Cyd; Tsai, Shengdar Q; Foley, Jonathan E; Sander, Jeffry D; Joung, J Keith

    2013-07-01

    Customized DNA-binding domains made using transcription activator-like effector (TALE) repeats are rapidly growing in importance as widely applicable research tools. TALE nucleases (TALENs), composed of an engineered array of TALE repeats fused to the FokI nuclease domain, have been used successfully for directed genome editing in various organisms and cell types. TALE transcription factors (TALE-TFs), consisting of engineered TALE repeat arrays linked to a transcriptional regulatory domain, have been used to up- or downregulate expression of endogenous genes in human cells and plants. This unit describes a detailed protocol for the recently described fast ligation-based automatable solid-phase high-throughput (FLASH) assembly method. FLASH enables automated high-throughput construction of engineered TALE repeats using an automated liquid handling robot or manually using a multichannel pipet. Using the automated approach, a single researcher can construct up to 96 DNA fragments encoding TALE repeat arrays of various lengths in a single day, and then clone these to construct sequence-verified TALEN or TALE-TF expression plasmids in a week or less. Plasmids required for FLASH are available by request from the Joung lab (http://eGenome.org). This unit also describes improvements to the Zinc Finger and TALE Targeter (ZiFiT Targeter) web server (http://ZiFiT.partners.org) that facilitate the design and construction of FLASH TALE repeat arrays in high throughput. © 2013 by John Wiley & Sons, Inc.

  5. Engineering Customized TALE Nucleases (TALENs) and TALE Transcription Factors by Fast Ligation-based Automatable Solid-phase High-throughput (FLASH) Assembly

    PubMed Central

    Reyon, Deepak; Maeder, Morgan L.; Khayter, Cyd; Tsai, Shengdar Q.; Foley, Jonathan E.; Sander, Jeffry D.; Joung, J. Keith

    2013-01-01

    Customized DNA-binding domains made using Transcription Activator-Like Effector (TALE) repeats are rapidly growing in importance as widely applicable research tools. TALE nucleases (TALENs), composed of an engineered array of TALE repeats fused to the FokI nuclease domain, have been used successfully for directed genome editing in multiple different organisms and cell types. TALE transcription factors (TALE-TFs), consisting of engineered TALE repeat arrays linked to a transcriptional regulatory domain, have been used to up- or down-regulate expression of endogenous genes in human cells and plants. Here we describe a detailed protocol for practicing the recently described Fast Ligation-based Automatable Solid-phase High-throughput (FLASH) assembly method. FLASH enables automated high-throughput construction of engineered TALE repeats using an automated liquid handling robot or manually using a multi-channel pipet. With the automated version of FLASH, a single researcher can construct up to 96 DNA fragments encoding various length TALE repeat arrays in one day and then clone these to construct sequence-verified TALEN or TALE-TF expression plasmids in one week or less. Plas-mids required to practice FLASH are available by request from the Joung Lab (http://www.jounglab.org/). We also describe here improvements to the Zinc Finger and TALE Targeter (ZiFiT Targeter) webserver (http://ZiFiTBeta.partners.org) that facilitate the design and construction of FLASH TALE repeat arrays in high-throughput. PMID:23821439

  6. The T-Cell Oncogene Tal2 Is a Target of PU.1 and Upregulated during Osteoclastogenesis

    PubMed Central

    Courtial, Nadine; Mücke, Christian; Herkt, Stefanie; Kolodziej, Stephan; Hussong, Helge; Lausen, Jörn

    2013-01-01

    Transcription factors play a crucial role in regulating differentiation processes during human life and are important in disease. The basic helix-loop-helix transcription factors Tal1 and Lyl1 play a major role in the regulation of gene expression in the hematopoietic system and are involved in human leukemia. Tal2, which belongs to the same family of transcription factors as Tal1 and Lyl1, is also involved in human leukaemia. However, little is known regarding the expression and regulation of Tal2 in hematopoietic cells. Here we show that Tal2 is expressed in hematopoietic cells of the myeloid lineage. Interestingly, we found that usage of the Tal2 promoter is different in human and mouse cells. Two promoters, hP1 and hP2 drive Tal2 expression in human erythroleukemia K562 cells, however in mouse RAW cells only the mP1 promoter is used. Furthermore, we found that Tal2 expression is upregulated during oesteoclastogenesis. We show that Tal2 is a direct target gene of the myeloid transcription factor PU.1, which is a key transcription factor for osteoclast gene expression. Strikingly, PU.1 binding to the P1 promoter is conserved between mouse and human, but PU.1 binding to P2 was only detected in human K562 cells. Additionally, we provide evidence that Tal2 influences the expression of the osteoclastic differentiation gene TRACP. These findings provide novel insight into the expression control of Tal2 in hematopoietic cells and reveal a function of Tal2 as a regulator of gene expression during osteoclast differentiation. PMID:24086757

  7. The subclonal complexity of STIL-TAL1+ T-cell acute lymphoblastic leukaemia.

    PubMed

    Furness, Caroline L; Mansur, Marcela B; Weston, Victoria J; Ermini, Luca; van Delft, Frederik W; Jenkinson, Sarah; Gale, Rosemary; Harrison, Christine J; Pombo-de-Oliveira, Maria S; Sanchez-Martin, Marta; Ferrando, Adolfo A; Kearns, Pamela; Titley, Ian; Ford, Anthony M; Potter, Nicola E; Greaves, Mel

    2018-03-20

    Single-cell genetics were used to interrogate clonal complexity and the sequence of mutational events in STIL-TAL1+ T-ALL. Single-cell multicolour FISH was used to demonstrate that the earliest detectable leukaemia subclone contained the STIL-TAL1 fusion and copy number loss of 9p21.3 (CDKN2A/CDKN2B locus), with other copy number alterations including loss of PTEN occurring as secondary subclonal events. In three cases, multiplex qPCR and phylogenetic analysis were used to produce branching evolutionary trees recapitulating the snapshot history of T-ALL evolution in this leukaemia subtype, which confirmed that mutations in key T-ALL drivers, including NOTCH1 and PTEN, were subclonal and reiterative in distinct subclones. Xenografting confirmed that self-renewing or propagating cells were genetically diverse. These data suggest that the STIL-TAL1 fusion is a likely founder or truncal event. Therapies targeting the TAL1 auto-regulatory complex are worthy of further investigation in T-ALL.

  8. Xanthomonas TAL effectors hijack host basal transcription factor IIA α and γ subunits for invasion.

    PubMed

    Ma, Ling; Wang, Qiang; Yuan, Meng; Zou, Tingting; Yin, Ping; Wang, Shiping

    2018-02-05

    The Xanthomonas genus includes Gram-negative plant-pathogenic bacteria, which infect a broad range of crops and wild plant species, cause symptoms with leaf blights, streaks, spots, stripes, necrosis, wilt, cankers and gummosis on leaves, stems and fruits in a wide variety of plants via injecting their effector proteins into the host cell during infection. Among these virulent effectors, transcription activator-like effectors (TALEs) interact with the γ subunit of host transcription factor IIA (TFIIAγ) to activate the transcription of host disease susceptibility genes. Functional TFIIA is a ternary complex comprising α, β and γ subunits. However, whether TALEs recruit TFIIAα, TFIIAβ, or both remains unknown. The underlying molecular mechanisms by which TALEs mediate host susceptibility gene activation require full elucidation. Here, we show that TALEs interact with the α+γ binary subcomplex but not the α+β+γ ternary complex of rice TFIIA (holo-OsTFIIA). The transcription factor binding (TFB) regions of TALEs, which are highly conserved in Xanthomonas species, have a dominant role in these interactions. Furthermore, the interaction between TALEs and the α+γ complex exhibits robust DNA binding activity in vitro. These results collectively demonstrate that TALE-carrying pathogens hijack the host basal transcription factors TFIIAα and TFIIAγ, but not TFIIAβ, to enhance host susceptibility during pathogen infection. The uncovered mechanism widens new insights on host-microbe interaction and provide an applicable strategy to breed high-resistance crop varieties. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Tall Tales of North America.

    ERIC Educational Resources Information Center

    Fresno City Unified School District, CA.

    Designed for use in junior high school language arts classes, this learning activity packet introduces students to North American folklore. Selected readings cover Indian tales, real folk heroes (Davy Crockett and John Henry), imaginary folk heroes (Paul Bunyan and Pecos Bill), Black folk stories (Brer Rabbit), and tales of Washington Irving. Each…

  10. TALE factors poise promoters for activation by Hox proteins.

    PubMed

    Choe, Seong-Kyu; Ladam, Franck; Sagerström, Charles G

    2014-01-27

    Hox proteins form complexes with TALE cofactors from the Pbx and Prep/Meis families to control transcription, but it remains unclear how Hox:TALE complexes function. Examining a Hoxb1b:TALE complex that regulates zebrafish hoxb1a transcription, we find maternally deposited TALE proteins at the hoxb1a promoter already during blastula stages. These TALE factors recruit histone-modifying enzymes to promote an active chromatin profile at the hoxb1a promoter and also recruit RNA polymerase II (RNAPII) and P-TEFb. However, in the presence of TALE factors, RNAPII remains phosphorylated on serine 5 and hoxb1a transcription is inefficient. By gastrula stages, Hoxb1b binds together with TALE factors to the hoxb1a promoter. This triggers P-TEFb-mediated transitioning of RNAPII to the serine 2-phosphorylated form and efficient hoxb1a transcription. We conclude that TALE factors access promoters during early embryogenesis to poise them for activation but that Hox proteins are required to trigger efficient transcription. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. A Transcription Activator-Like Effector (TALE) Toolbox for Genome Engineering

    PubMed Central

    Sanjana, Neville E.; Cong, Le; Zhou, Yang; Cunniff, Margaret M.; Feng, Guoping; Zhang, Feng

    2013-01-01

    Transcription activator-like effectors (TALEs) are a class of naturally occurring DNA binding proteins found in the plant pathogen Xanthomonas sp. The DNA binding domain of each TALE consists of tandem 34-amino acid repeat modules that can be rearranged according to a simple cipher to target new DNA sequences. Customized TALEs can be used for a wide variety of genome engineering applications, including transcriptional modulation and genome editing. Here we describe a toolbox for rapid construction of custom TALE transcription factors (TALE-TFs) and nucleases (TALENs) using a hierarchical ligation procedure. This toolbox facilitates affordable and rapid construction of custom TALE-TFs and TALENs within one week and can be easily scaled up to construct TALEs for multiple targets in parallel. We also provide details for testing the activity in mammalian cells of custom TALE-TFs and TALENs using, respectively, qRT-PCR and Surveyor nuclease. The TALE toolbox described here will enable a broad range of biological applications. PMID:22222791

  12. A Conserved Basal Transcription Factor Is Required for the Function of Diverse TAL Effectors in Multiple Plant Hosts.

    PubMed

    Huang, Renyan; Hui, Shugang; Zhang, Meng; Li, Pei; Xiao, Jinghua; Li, Xianghua; Yuan, Meng; Wang, Shiping

    2017-01-01

    Many Xanthomonas bacteria use transcription activator-like effector (TALE) proteins to activate plant disease susceptibility ( S ) genes, and this activation contributes to disease. We recently reported that rice basal transcription factor IIA gamma subunit, OsTFIIAγ5, is hijacked by TALE-carrying Xanthomonas oryzae infecting the plants. However, whether TFIIAγs are also involved in TALE-carrying Xanthomonas -caused diseases in other plants is unknown. Here, molecular and genetic approaches were used to investigate the role of TFIIAγs in other plants. We found that TFIIAγs are also used by TALE-carrying Xanthomonas to cause disease in other plants. The TALEs of Xanthomonas citri pv. citri ( Xcc ) causing canker in citrus and Xanthomonas campestris pv. vesicatoria ( Xcv ) causing bacterial spot in pepper and tomato interacted with corresponding host TFIIAγs as in rice. Transcriptionally suppressing TFIIAγ led to resistance to Xcc in citrus and Xcv in pepper and tomato. The 39th residue of OsTFIIAγ5 and citrus CsTFIIAγ is vital for TALE-dependent induction of plant S genes. As mutated OsTFIIAγ5 V 39E , CsTFIIAγ V 39E , pepper CaTFIIAγ V 39E , and tomato SlTFIIAγ V 39E also did not interact with TALEs to prevent disease. These results suggest that TALE-carrying bacteria share a common mechanism for infecting plants. Using TFIIAγ V 39E -type mutation could be a general strategy for improving resistance to TALE-carrying pathogens in crops.

  13. Generation of dTALEs and Libraries of Synthetic TALE-Activated Promoters for Engineering of Gene Regulatory Networks in Plants.

    PubMed

    Schreiber, Tom; Tissier, Alain

    2017-01-01

    Transcription factors with programmable DNA-binding specificity constitute valuable tools for the design of orthogonal gene regulatory networks for synthetic biology. Transcription activator-like effectors (TALEs), as natural transcription regulators, were used to design, build, and test libraries of synthetic TALE-activated promoters (STAPs) that show a broad range of expression levels in plants. In this chapter, we present protocols for the construction of artificial TALEs and corresponding STAPs.

  14. Telescope Array Low energy Extension: TALE

    NASA Astrophysics Data System (ADS)

    Ogio, Shoichi

    TALE, the Telescope Array Low Energy extension was designed to lower the energy threshold to about 1016.5 eV. TALE has a surface detector (SD) array made up of 103 scintillation counters (40 with 400 m spacing, 36 with 600 m spacing and 27 with 1.2 km spacing) and a Fluorescence Detector (FD) station consisting of ten FD telescopes working with the Telescope Array Middle Drum FD station, which is made up of 14 telescopes. TALE-FD full operation started in 2013 and the SD array was partially-completed with 16 SDs and continues the operation from 2014. We will describe the history and the current status of the detectors and will make a brief report about the FD and the hybrid analysis results. TALE detector will be completed as a hybrid air shower detector in 2018. We will report the technical details of the detectors, the schedule and the expected performances.

  15. Morality's ugly implications in Oscar Wilde's fairy tales.

    PubMed

    Jones, Justin T

    2011-01-01

    In Oscar Wilde's two volumes of fairy tales, "The Happy Prince" and Other Tales (1888) and A House of Pomegranates (1891), many central characters meet with premature death or physical disfigurement after learning a bourgeois moral lesson. In an attempt to explain this unconventional phenomenon in the fairy tale tradition, this essay examines Wilde's stories through the lens of his aesthetic ideology and demonstrates how the superficial morality of the Victorian bourgeoisie corrodes each tale's aesthetic integrity, causing the characters to either deny morality outright, assume the guise of Christian philanthropy, or die as the result of their moral reformation.

  16. Through Fairy-Tales to Math in the Lessons

    ERIC Educational Resources Information Center

    Andersone, Rudite

    2009-01-01

    Every person in his lifetime has many times experienced the miraculous impact of the fairy-tale on his imagination, mind and feelings. But we seldom reflect upon the content not only in the ethical aspect of fairy-tales but also as a source of different kinds of knowledge, among them the knowledge of mathematics. The use of fairy-tales in lessons…

  17. Unoriginal tales

    NASA Astrophysics Data System (ADS)

    Sudbery, Tony

    2012-03-01

    In his article "Other-worldly tales" (December 2011 pp18-19), Robert P Crease describes Hugh Everett's idea of branching universes or "many worlds" as "one of the strangest ideas in the history of thought, and the inspiration for many science-fiction stories".

  18. TALE proteins search DNA using a rotationally decoupled mechanism.

    PubMed

    Cuculis, Luke; Abil, Zhanar; Zhao, Huimin; Schroeder, Charles M

    2016-10-01

    Transcription activator-like effector (TALE) proteins are a class of programmable DNA-binding proteins used extensively for gene editing. Despite recent progress, however, little is known about their sequence search mechanism. Here, we use single-molecule experiments to study TALE search along DNA. Our results show that TALEs utilize a rotationally decoupled mechanism for nonspecific search, despite remaining associated with DNA templates during the search process. Our results suggest that the protein helical structure enables TALEs to adopt a loosely wrapped conformation around DNA templates during nonspecific search, facilitating rapid one-dimensional (1D) diffusion under a range of solution conditions. Furthermore, this model is consistent with a previously reported two-state mechanism for TALE search that allows these proteins to overcome the search speed-stability paradox. Taken together, our results suggest that TALE search is unique among the broad class of sequence-specific DNA-binding proteins and supports efficient 1D search along DNA.

  19. Rapid and accurate synthesis of TALE genes from synthetic oligonucleotides.

    PubMed

    Wang, Fenghua; Zhang, Hefei; Gao, Jingxia; Chen, Fengjiao; Chen, Sijie; Zhang, Cuizhen; Peng, Gang

    2016-01-01

    Custom synthesis of transcription activator-like effector (TALE) genes has relied upon plasmid libraries of pre-fabricated TALE-repeat monomers or oligomers. Here we describe a novel synthesis method that directly incorporates annealed synthetic oligonucleotides into the TALE-repeat units. Our approach utilizes iterative sets of oligonucleotides and a translational frame check strategy to ensure the high efficiency and accuracy of TALE-gene synthesis. TALE arrays of more than 20 repeats can be constructed, and the majority of the synthesized constructs have perfect sequences. In addition, this novel oligonucleotide-based method can readily accommodate design changes to the TALE repeats. We demonstrated an increased gene targeting efficiency against a genomic site containing a potentially methylated cytosine by incorporating non-conventional repeat variable di-residue (RVD) sequences.

  20. PADI4 acts as a coactivator of Tal1 by counteracting repressive histone arginine methylation

    NASA Astrophysics Data System (ADS)

    Kolodziej, Stephan; Kuvardina, Olga N.; Oellerich, Thomas; Herglotz, Julia; Backert, Ingo; Kohrs, Nicole; Buscató, Estel. La; Wittmann, Sandra K.; Salinas-Riester, Gabriela; Bonig, Halvard; Karas, Michael; Serve, Hubert; Proschak, Ewgenij; Lausen, Jörn

    2014-05-01

    The transcription factor Tal1 is a critical activator or repressor of gene expression in hematopoiesis and leukaemia. The mechanism by which Tal1 differentially influences transcription of distinct genes is not fully understood. Here we show that Tal1 interacts with the peptidylarginine deiminase IV (PADI4). We demonstrate that PADI4 can act as an epigenetic coactivator through influencing H3R2me2a. At the Tal1/PADI4 target gene IL6ST the repressive H3R2me2a mark triggered by PRMT6 is counteracted by PADI4, which augments the active H3K4me3 mark and thus increases IL6ST expression. In contrast, at the CTCF promoter PADI4 acts as a repressor. We propose that the influence of PADI4 on IL6ST transcription plays a role in the control of IL6ST expression during lineage differentiation of hematopoietic stem/progenitor cells. These results open the possibility to pharmacologically influence Tal1 in leukaemia.

  1. The Epistemic Value of Cautionary Tales

    ERIC Educational Resources Information Center

    Shields, William M.

    2006-01-01

    A cautionary tale has become something of a cottage industry in the past decade. To be sure, there has been plenty of material for these publications: Bhopal, Chernobyl, "Exxon Valdez," Three Mile Island, and "Challenger" have entered the lexicon as virtual synonyms for "disaster." Cautionary tale scenarios involve a different kind of causality.…

  2. Directed evolution of the TALE N-terminal domain for recognition of all 5' bases.

    PubMed

    Lamb, Brian M; Mercer, Andrew C; Barbas, Carlos F

    2013-11-01

    Transcription activator-like effector (TALE) proteins can be designed to bind virtually any DNA sequence. General guidelines for design of TALE DNA-binding domains suggest that the 5'-most base of the DNA sequence bound by the TALE (the N0 base) should be a thymine. We quantified the N0 requirement by analysis of the activities of TALE transcription factors (TALE-TF), TALE recombinases (TALE-R) and TALE nucleases (TALENs) with each DNA base at this position. In the absence of a 5' T, we observed decreases in TALE activity up to >1000-fold in TALE-TF activity, up to 100-fold in TALE-R activity and up to 10-fold reduction in TALEN activity compared with target sequences containing a 5' T. To develop TALE architectures that recognize all possible N0 bases, we used structure-guided library design coupled with TALE-R activity selections to evolve novel TALE N-terminal domains to accommodate any N0 base. A G-selective domain and broadly reactive domains were isolated and characterized. The engineered TALE domains selected in the TALE-R format demonstrated modularity and were active in TALE-TF and TALEN architectures. Evolved N-terminal domains provide effective and unconstrained TALE-based targeting of any DNA sequence as TALE binding proteins and designer enzymes.

  3. TALE-mediated modulation of transcriptional enhancers in vivo.

    PubMed

    Crocker, Justin; Stern, David L

    2013-08-01

    We tested whether transcription activator-like effectors (TALEs) could mediate repression and activation of endogenous enhancers in the Drosophila genome. TALE repressors (TALERs) targeting each of the five even-skipped (eve) stripe enhancers generated repression specifically of the focal stripes. TALE activators (TALEAs) targeting the eve promoter or enhancers caused increased expression primarily in cells normally activated by the promoter or targeted enhancer, respectively. This effect supports the view that repression acts in a dominant fashion on transcriptional activators and that the activity state of an enhancer influences TALE binding or the ability of the VP16 domain to enhance transcription. In these assays, the Hairy repression domain did not exhibit previously described long-range transcriptional repression activity. The phenotypic effects of TALER and TALEA expression in larvae and adults are consistent with the observed modulations of eve expression. TALEs thus provide a novel tool for detection and functional modulation of transcriptional enhancers in their native genomic context.

  4. Folk Tales, Fairy Tales, and History: Uses and Classification.

    ERIC Educational Resources Information Center

    Claremont, Francesca

    1993-01-01

    Compiles excerpts from two 1964 lectures that examine the use of folk and fairy tales for the teaching of prehistory, geography, and grammar. Provides a starting point for thinking about the power of literature as an integrating medium in the Montessori elementary classroom. (HTH)

  5. Quantitative analysis of TALE-DNA interactions suggests polarity effects.

    PubMed

    Meckler, Joshua F; Bhakta, Mital S; Kim, Moon-Soo; Ovadia, Robert; Habrian, Chris H; Zykovich, Artem; Yu, Abigail; Lockwood, Sarah H; Morbitzer, Robert; Elsäesser, Janett; Lahaye, Thomas; Segal, David J; Baldwin, Enoch P

    2013-04-01

    Transcription activator-like effectors (TALEs) have revolutionized the field of genome engineering. We present here a systematic assessment of TALE DNA recognition, using quantitative electrophoretic mobility shift assays and reporter gene activation assays. Within TALE proteins, tandem 34-amino acid repeats recognize one base pair each and direct sequence-specific DNA binding through repeat variable di-residues (RVDs). We found that RVD choice can affect affinity by four orders of magnitude, with the relative RVD contribution in the order NG > HD ≈ NN > NI > NK. The NN repeat preferred the base G over A, whereas the NK repeat bound G with 10(3)-fold lower affinity. We compared AvrBs3, a naturally occurring TALE that recognizes its target using some atypical RVD-base combinations, with a designed TALE that precisely matches 'standard' RVDs with the target bases. This comparison revealed unexpected differences in sensitivity to substitutions of the invariant 5'-T. Another surprising observation was that base mismatches at the 5' end of the target site had more disruptive effects on affinity than those at the 3' end, particularly in designed TALEs. These results provide evidence that TALE-DNA recognition exhibits a hitherto un-described polarity effect, in which the N-terminal repeats contribute more to affinity than C-terminal ones.

  6. Robust, synergistic regulation of human gene expression using TALE activators.

    PubMed

    Maeder, Morgan L; Linder, Samantha J; Reyon, Deepak; Angstman, James F; Fu, Yanfang; Sander, Jeffry D; Joung, J Keith

    2013-03-01

    Artificial activators designed using transcription activator-like effector (TALE) technology have broad utility, but previous studies suggest that these monomeric proteins often exhibit low activities. Here we demonstrate that TALE activators can robustly function individually or in synergistic combinations to increase expression of endogenous human genes over wide dynamic ranges. These findings will encourage applications of TALE activators for research and therapy, and guide design of monomeric TALE-based fusion proteins.

  7. Excitations Élémentaires au Voisinage de la Surface de Séparation d'un Métal Normal et d'un Métal Supraconducteur

    NASA Astrophysics Data System (ADS)

    Saint-James, Par D.

    On étudie le spectre d'excitation pour une couche de métal normal déposée sur un supraconducteur. On montre que si l'interaction attractive électron-électron est négligeable dans le métal normal, il n'y a pas de gap d'énergie dans le spectre d'excitation, même si l'épaisseur de la couche normale est petite. Une étude analogue, conduisant à une conclusion similaire, est menée pour deux supraconducteurs accolés et pour des sphères de métal normal baignant dans un supraconducteur. L'effet prévu pourrait expliquer quelques résultats particuliers observés dans des mesures d'effet tunnel dans des supraconducteurs durs. The excitation spectrum of a layer of normal metal (N) deposited on a superconducting substrate (S) is discussed. It is shown that if the electron-electron attractive interaction is negligibly small in (N) there is no energy gap in the excitation spectrum even if the thickness of the layer (N) is small. A similar study, with equivalent conclusions, has been carried out for two superconductors and for normal metal spheres embedded in a superconductor. The effect may possibly explain some peculiar results of tunnelling experiments on hard superconductors.

  8. Design, Assembly, and Characterization of TALE-Based Transcriptional Activators and Repressors.

    PubMed

    Thakore, Pratiksha I; Gersbach, Charles A

    2016-01-01

    Transcription activator-like effectors (TALEs) are modular DNA-binding proteins that can be fused to a variety of effector domains to regulate the epigenome. Nucleotide recognition by TALE monomers follows a simple cipher, making this a powerful and versatile method to activate or repress gene expression. Described here are methods to design, assemble, and test TALE transcription factors (TALE-TFs) for control of endogenous gene expression. In this protocol, TALE arrays are constructed by Golden Gate cloning and tested for activity by transfection and quantitative RT-PCR. These methods for engineering TALE-TFs are useful for studies in reverse genetics and genomics, synthetic biology, and gene therapy.

  9. Design, Assembly, and Characterization of TALE-Based Transcriptional Activators and Repressors

    PubMed Central

    Thakore, Pratiksha I.; Gersbach, Charles A.

    2016-01-01

    Transcription activator-like effectors (TALEs) are modular DNA-binding proteins that can be fused to a variety of effector domains to regulate the epigenome. Nucleotide recognition by TALE monomers follows a simple cipher, making this a powerful and versatile method to activate or repress gene expression. Described here are methods to design, assemble, and test TALE transcription factors (TALE-TFs) for control of endogenous gene expression. In this protocol, TALE arrays are constructed by Golden Gate cloning and tested for activity by transfection and quantitative RT-PCR. These methods for engineering TALE-TFs are useful for studies in reverse genetics and genomics, synthetic biology, and gene therapy. PMID:26443215

  10. Spatial resolution limits for the isotropic-3D PET detector X’tal cube

    NASA Astrophysics Data System (ADS)

    Yoshida, Eiji; Tashima, Hideaki; Hirano, Yoshiyuki; Inadama, Naoko; Nishikido, Fumihiko; Murayama, Hideo; Yamaya, Taiga

    2013-11-01

    Positron emission tomography (PET) has become a popular imaging method in metabolism, neuroscience, and molecular imaging. For dedicated human brain and small animal PET scanners, high spatial resolution is needed to visualize small objects. To improve the spatial resolution, we are developing the X’tal cube, which is our new PET detector to achieve isotropic 3D positioning detectability. We have shown that the X’tal cube can achieve 1 mm3 uniform crystal identification performance with the Anger-type calculation even at the block edges. We plan to develop the X’tal cube with even smaller 3D grids for sub-millimeter crystal identification. In this work, we investigate spatial resolution of a PET scanner based on the X’tal cube using Monte Carlo simulations for predicting resolution performance in smaller 3D grids. For spatial resolution evaluation, a point source emitting 511 keV photons was simulated by GATE for all physical processes involved in emission and interaction of positrons. We simulated two types of animal PET scanners. The first PET scanner had a detector ring 14.6 cm in diameter composed of 18 detectors. The second PET scanner had a detector ring 7.8 cm in diameter composed of 12 detectors. After the GATE simulations, we converted the interacting 3D position information to digitalized positions for realistic segmented crystals. We simulated several X’tal cubes with cubic crystals from (0.5 mm)3 to (2 mm)3 in size. Also, for evaluating the effect of DOI resolution, we simulated several X’tal cubes with crystal thickness from (0.5 mm)3 to (9 mm)3. We showed that sub-millimeter spatial resolution was possible using cubic crystals smaller than (1.0 mm)3 even with the assumed physical processes. Also, the weighted average spatial resolutions of both PET scanners with (0.5 mm)3 cubic crystals were 0.53 mm (14.6 cm ring diameter) and 0.48 mm (7.8 cm ring diameter). For the 7.8 cm ring diameter, spatial resolution with 0.5×0.5×1.0 mm3 crystals

  11. Happily, Ever After: The Resilience of the Fairy Tale, Part 1.

    ERIC Educational Resources Information Center

    Hearn, Michael Patrick

    1998-01-01

    Discusses the work of Frenchman Charles Perrault, the seminal figure in fairy tales, and puts it in context of the French fairy tale fashion. Describes how the fairy tale came to England. Describes how the Germans revived the fairy tale at the end of the 18th century, and discusses the work of the Brothers Grimm. (SR)

  12. Functions and impact of tal-like genes in animals with regard to applied aspects.

    PubMed

    Zhu, Min; Hu, Xiaolong; Cao, Guangli; Xue, Renyu; Gong, Chengliang

    2018-06-16

    A large number of DNAs in eukaryote genomes can code for atypical transcripts, and their functions are controversial. It has been reported that the transcripts contain many small open reading frames (sORFs), which were originally considered as non-translatable RNAs. However, increasing evidence has suggested that some of these sORFs can encode for small peptides and some are conserved across large evolutionary distances. It has been reported that the small peptides have functions and may be involved in varieties of cellular processes, playing important roles in development, physiology, and metabolism. Among the sORFs, studies of the non-canonical gene polished rice/tarsal-less (pri/tal) in Drosophila and mille-pattes(mlpt) in Tribolium have been more thoroughly studied. The genes similar to pri/tal in other species have been defined as the tarsal-less-related gene family, tal-like gene. In this review, we described recent progress in the discovery and functional characterization of the small peptides encoded by the tal-like gene and their possible functional potentials.

  13. [Transcription activator-like effectors(TALEs)based genome engineering].

    PubMed

    Zhao, Mei-Wei; Duan, Cheng-Li; Liu, Jiang

    2013-10-01

    Systematic reverse-engineering of functional genome architecture requires precise modifications of gene sequences and transcription levels. The development and application of transcription activator-like effectors(TALEs) has created a wealth of genome engineering possibilities. TALEs are a class of naturally occurring DNA-binding proteins found in the plant pathogen Xanthomonas species. The DNA-binding domain of each TALE typically consists of tandem 34-amino acid repeat modules rearranged according to a simple cipher to target new DNA sequences. Customized TALEs can be used for a wide variety of genome engineering applications, including transcriptional modulation and genome editing. Such "genome engineering" has now been established in human cells and a number of model organisms, thus opening the door to better understanding gene function in model organisms, improving traits in crop plants and treating human genetic disorders.

  14. Direct observation of TALE protein dynamics reveals a two-state search mechanism.

    PubMed

    Cuculis, Luke; Abil, Zhanar; Zhao, Huimin; Schroeder, Charles M

    2015-06-01

    Transcription activator-like effector (TALE) proteins are a class of programmable DNA-binding proteins for which the fundamental mechanisms governing the search process are not fully understood. Here we use single-molecule techniques to directly observe TALE search dynamics along DNA templates. We find that TALE proteins are capable of rapid diffusion along DNA using a combination of sliding and hopping behaviour, which suggests that the TALE search process is governed in part by facilitated diffusion. We also observe that TALE proteins exhibit two distinct modes of action during the search process-a search state and a recognition state-facilitated by different subdomains in monomeric TALE proteins. Using TALE truncation mutants, we further demonstrate that the N-terminal region of TALEs is required for the initial non-specific binding and subsequent rapid search along DNA, whereas the central repeat domain is required for transitioning into the site-specific recognition state.

  15. [Development of a Japanese version of the TALE scale].

    PubMed

    Ochiai, Tsutomu; Oguchi, Takashi

    2013-12-01

    The Thinking About Life Experiences (TALE) Scale (Bluck & Alea, 2011) has three subscales that assess the self, social, and directive functions of autobiographical memory. This study constructs a Japanese version of the TALE Scale and examines its reliability and validity. Fifteen items that assess the three functions of autobiographical memory were translated into Japanese. We conducted an online investigation with 600 men and women between 20-59 years of age. In Study 1, exploratory and confirmatory factor analysis identified that the three-factor structure of the Japanese version of the TALE Scale was the same as the original TALE Scale. Sufficient internal consistency of the scale was found, and the construct validity of the scale was supported by correlation analysis. Study 2 confirmed that the test-retest reliabilities of the three subscales were sufficient. Thus, this Japanese version of the TALE Scale is useful to assess autobiographical memory functions in Japan.

  16. Directed evolution of the TALE N-terminal domain for recognition of all 5′ bases

    PubMed Central

    Lamb, Brian M.; Mercer, Andrew C.; Barbas, Carlos F.

    2013-01-01

    Transcription activator-like effector (TALE) proteins can be designed to bind virtually any DNA sequence. General guidelines for design of TALE DNA-binding domains suggest that the 5′-most base of the DNA sequence bound by the TALE (the N0 base) should be a thymine. We quantified the N0 requirement by analysis of the activities of TALE transcription factors (TALE-TF), TALE recombinases (TALE-R) and TALE nucleases (TALENs) with each DNA base at this position. In the absence of a 5′ T, we observed decreases in TALE activity up to >1000-fold in TALE-TF activity, up to 100-fold in TALE-R activity and up to 10-fold reduction in TALEN activity compared with target sequences containing a 5′ T. To develop TALE architectures that recognize all possible N0 bases, we used structure-guided library design coupled with TALE-R activity selections to evolve novel TALE N-terminal domains to accommodate any N0 base. A G-selective domain and broadly reactive domains were isolated and characterized. The engineered TALE domains selected in the TALE-R format demonstrated modularity and were active in TALE-TF and TALEN architectures. Evolved N-terminal domains provide effective and unconstrained TALE-based targeting of any DNA sequence as TALE binding proteins and designer enzymes. PMID:23980031

  17. Conformational elasticity can facilitate TALE-DNA recognition

    PubMed Central

    Lei, Hongxing; Sun, Jiya; Baldwin, Enoch P.; Segal, David J.; Duan, Yong

    2015-01-01

    Sequence-programmable transcription activator-like effector (TALE) proteins have emerged as a highly efficient tool for genome engineering. Recent crystal structures depict a transition between an open unbound solenoid and more compact DNA-bound solenoid formed by the 34 amino acid repeats. How TALEs switch conformation between these two forms without substantial energetic compensation, and how the repeat-variable di-residues (RVDs) discriminate between the cognate base and other bases still remain unclear. Computational analysis on these two aspects of TALE-DNA interaction mechanism has been conducted in order to achieve a better understanding of the energetics. High elasticity was observed in the molecular dynamics simulations of DNA-free TALE structure that started from the bound conformation where it sampled a wide range of conformations including the experimentally determined apo- and bound- conformations. This elastic feature was also observed in the simulations starting from the apo form which suggests low free energy barrier between the two conformations and small compensation required upon binding. To analyze binding specificity, we performed free energy calculations of various combinations of RVDs and bases using Poisson-Boltzmann/surface area (PBSA) and other approaches. The PBSA calculations indicated that the native RVD-base structures had lower binding free energy than mismatched structures for most of the RVDs examined. Our theoretical analyses provided new insight on the dynamics and energetics of TALE-DNA binding mechanism. PMID:24629191

  18. Direct observation of TALE protein dynamics reveals a two-state search mechanism

    PubMed Central

    Cuculis, Luke; Abil, Zhanar; Zhao, Huimin; Schroeder, Charles M.

    2015-01-01

    Transcription activator-like effector (TALE) proteins are a class of programmable DNA-binding proteins for which the fundamental mechanisms governing the search process are not fully understood. Here we use single-molecule techniques to directly observe TALE search dynamics along DNA templates. We find that TALE proteins are capable of rapid diffusion along DNA using a combination of sliding and hopping behaviour, which suggests that the TALE search process is governed in part by facilitated diffusion. We also observe that TALE proteins exhibit two distinct modes of action during the search process—a search state and a recognition state—facilitated by different subdomains in monomeric TALE proteins. Using TALE truncation mutants, we further demonstrate that the N-terminal region of TALEs is required for the initial non-specific binding and subsequent rapid search along DNA, whereas the central repeat domain is required for transitioning into the site-specific recognition state. PMID:26027871

  19. Happily Ever After? Teens and Fairy Tales.

    ERIC Educational Resources Information Center

    Tuccillo, Diane P.

    2001-01-01

    Argues, from the author's experience and with supporting quotes from many teenagers, that modern retellings of classic fairy tales can be very popular with teenage readers. Discusses numerous such stories, and offers an extensive list of retold fairy tales, organized into: Cinderella stories, Beauty and the Beast stories, Sleeping Beauty stories,…

  20. Chimeric TALE recombinases with programmable DNA sequence specificity.

    PubMed

    Mercer, Andrew C; Gaj, Thomas; Fuller, Roberta P; Barbas, Carlos F

    2012-11-01

    Site-specific recombinases are powerful tools for genome engineering. Hyperactivated variants of the resolvase/invertase family of serine recombinases function without accessory factors, and thus can be re-targeted to sequences of interest by replacing native DNA-binding domains (DBDs) with engineered zinc-finger proteins (ZFPs). However, imperfect modularity with particular domains, lack of high-affinity binding to all DNA triplets, and difficulty in construction has hindered the widespread adoption of ZFPs in unspecialized laboratories. The discovery of a novel type of DBD in transcription activator-like effector (TALE) proteins from Xanthomonas provides an alternative to ZFPs. Here we describe chimeric TALE recombinases (TALERs): engineered fusions between a hyperactivated catalytic domain from the DNA invertase Gin and an optimized TALE architecture. We use a library of incrementally truncated TALE variants to identify TALER fusions that modify DNA with efficiency and specificity comparable to zinc-finger recombinases in bacterial cells. We also show that TALERs recombine DNA in mammalian cells. The TALER architecture described herein provides a platform for insertion of customized TALE domains, thus significantly expanding the targeting capacity of engineered recombinases and their potential applications in biotechnology and medicine.

  1. Introducing Children to Folk Tales. Bill Harp Professional Teachers Library.

    ERIC Educational Resources Information Center

    Weir, Beth

    This book provides K-8 teachers with an introductory resource on folk tales. The book acknowledges that teachers are often very interested in folk tales but lack the time to research them. Each chapter contains some background information on a story type or a character. The book's six chapters are as follows: (1) "The Folk Tale Tradition"; (2)…

  2. Conformational elasticity can facilitate TALE-DNA recognition.

    PubMed

    Lei, Hongxing; Sun, Jiya; Baldwin, Enoch P; Segal, David J; Duan, Yong

    2014-01-01

    Sequence-programmable transcription activator-like effector (TALE) proteins have emerged as a highly efficient tool for genome engineering. Recent crystal structures depict a transition between an open unbound solenoid and more compact DNA-bound solenoid formed by the 34 amino acid repeats. How TALEs switch conformation between these two forms without substantial energetic compensation, and how the repeat-variable di-residues (RVDs) discriminate between the cognate base and other bases still remain unclear. Computational analysis on these two aspects of TALE-DNA interaction mechanism has been conducted in order to achieve a better understanding of the energetics. High elasticity was observed in the molecular dynamics simulations of DNA-free TALE structure that started from the bound conformation where it sampled a wide range of conformations including the experimentally determined apo and bound conformations. This elastic feature was also observed in the simulations starting from the apo form which suggests low free energy barrier between the two conformations and small compensation required upon binding. To analyze binding specificity, we performed free energy calculations of various combinations of RVDs and bases using Poisson-Boltzmann surface area (PBSA) and other approaches. The PBSA calculations indicated that the native RVD-base structures had lower binding free energy than mismatched structures for most of the RVDs examined. Our theoretical analyses provided new insight on the dynamics and energetics of TALE-DNA binding mechanism. © 2014 Elsevier Inc. All rights reserved.

  3. Teaching the "A" Level Text: "The Wife of Bath's Prologue and Tale."

    ERIC Educational Resources Information Center

    Spraggs, Gillian

    1988-01-01

    Presents an approach for teaching Chaucer's "Wife of Bath's Prologue and Tale" (from "The Canterbury Tales"). Recommends several reference texts related to the "The Canterbury Tales" and medieval literature in general. (MM)

  4. Visualization of specific repetitive genomic sequences with fluorescent TALEs in Arabidopsis thaliana

    PubMed Central

    Fujimoto, Satoru; Sugano, Shigeo S.; Kuwata, Keiko; Osakabe, Keishi; Matsunaga, Sachihiro

    2016-01-01

    Live imaging of the dynamics of nuclear organization provides the opportunity to uncover the mechanisms responsible for four-dimensional genome architecture. Here, we describe the use of fluorescent protein (FP) fusions of transcription activator-like effectors (TALEs) to visualize endogenous genomic sequences in Arabidopsis thaliana. The ability to engineer sequence-specific TALEs permits the investigation of precise genomic sequences. We could detect TALE-FP signals associated with centromeric, telomeric, and rDNA repeats and the signal distribution was consistent with that observed by fluorescent in situ hybridization. TALE-FPs are advantageous because they permit the observation of intact tissues. We used our TALE-FP method to investigate the nuclei of several multicellular plant tissues including roots, hypocotyls, leaves, and flowers. Because TALE-FPs permit live-cell imaging, we successfully observed the temporal dynamics of centromeres and telomeres in plant organs. Fusing TALEs to multimeric FPs enhanced the signal intensity when observing telomeres. We found that the mobility of telomeres was different in sub-nuclear regions. Transgenic plants stably expressing TALE-FPs will provide new insights into chromatin organization and dynamics in multicellular organisms. PMID:27811079

  5. Ladrillo and Tales of Juan Bobo: Puerto Rican Folk Tales.

    ERIC Educational Resources Information Center

    Matos, Reinaldo; Matos, Ana

    These two illustrated elementary readers contain the Spanish and English versions of the Puerto Rican folk tales, "Ladrillo" and "Cuentos de Juan Bobo." They are part of a series of reading materials for elementary-level migrant children. These materials are intended to help the child relate to his culture, develop interest in…

  6. Recovering Native Traditions and Tales for Younger Readers.

    ERIC Educational Resources Information Center

    Stott, Jon C.

    1995-01-01

    Reviews 14 children's books concerned with traditional Native American tales and experiences, written mostly by Native authors and published 1989-93. Includes books on Hiawatha, buffalo, the battle of the Little Bighorn, the Fetterman Fight, and traditional beliefs and values; Cree, Navajo, Chickasaw, and Seneca tales and stories; fictional…

  7. 50 CFR 648.231 - Spiny dogfish Annual Catch Target (ACT) and Total Allowable Level of Landings (TAL).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ACT and TAL recommendation process. (1) The ACT shall be identified as less than or equal to the ACL... conduct a detailed review of fishery performance relative to TALs in conjunction with any ACL performance...

  8. 50 CFR 648.231 - Spiny dogfish Annual Catch Target (ACT) and Total Allowable Level of Landings (TAL).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ACT and TAL recommendation process. (1) The ACT shall be identified as less than or equal to the ACL... conduct a detailed review of fishery performance relative to TALs in conjunction with any ACL performance...

  9. 50 CFR 648.231 - Spiny dogfish Annual Catch Target (ACT) and Total Allowable Level of Landings (TAL).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ACT and TAL recommendation process. (1) The ACT shall be identified as less than or equal to the ACL... conduct a detailed review of fishery performance relative to TALs in conjunction with any ACL performance...

  10. Direct observation of transcription activator-like effector (TALE) protein dynamics

    NASA Astrophysics Data System (ADS)

    Cuculis, Luke; Abil, Zhanar; Zhao, Huimin; Schroeder, Charles M.

    2014-03-01

    In this work, we describe a single molecule assay to probe the site-search dynamics of transcription activator-like effector (TALE) proteins along DNA. In modern genetics, the ability to selectively edit the human genome is an unprecedented development, driven by recent advances in targeted nuclease proteins. Specific gene editing can be accomplished using TALE proteins, which are programmable DNA-binding proteins that can be fused to a nuclease domain. In this way, TALENs are a leading technology that has shown great success in the genomic editing of pluripotent stem cells. A major hurdle facing clinical implementation, however, is the potential for deleterious off-target binding events. For these reasons, a molecular-level understanding of TALE binding and target sequence search on DNA is essential. To this end, we developed a single-molecule fluorescence imaging assay that provides a first-of-its-kind view of the 1-D diffusion of TALE proteins along stretched DNA. Taken together with co-crystal structures of DNA-bound TALEs, our results suggest a rotationally-coupled, major groove tracking model for diffusion. We further report diffusion constants for TALE proteins as a function of salt concentration, consistent with previously described models of 1-D protein diffusion.

  11. Engineering DNA Backbone Interactions Results in TALE Scaffolds with Enhanced 5-Methylcytosine Selectivity.

    PubMed

    Rathi, Preeti; Witte, Anna; Summerer, Daniel

    2017-11-08

    Transcription activator-like effectors (TALEs) are DNA major-groove binding proteins widely used for genome targeting. TALEs contain an N-terminal region (NTR) and a central repeat domain (CRD). Repeats of the CRD selectively recognize each one DNA nucleobase, offering programmability. Moreover, repeats with selectivity for 5-methylcytosine (5mC) and its oxidized derivatives can be designed for analytical applications. However, both TALE domains also nonspecifically interact with DNA phosphates via basic amino acids. To enhance the 5mC selectivity of TALEs, we aimed to decrease the nonselective binding energy of TALEs. We substituted basic amino acids with alanine in the NTR and identified TALE mutants with increased selectivity. We then analysed conserved, DNA phosphate-binding KQ diresidues in CRD repeats and identified further improved mutants. Combination of mutations in the NTR and CRD was highly synergetic and resulted in TALE scaffolds with up to 4.3-fold increased selectivity in genomic 5mC analysis via affinity enrichment. Moreover, transcriptional activation in HEK293T cells by a TALE-VP64 construct based on this scaffold design exhibited a 3.5-fold increased 5mC selectivity. This provides perspectives for improved 5mC analysis and for the 5mC-conditional control of TALE-based editing constructs in vivo.

  12. Larger than Life: Reading and Writing Tall Tales

    ERIC Educational Resources Information Center

    Tunks, Karyn

    2008-01-01

    The genre of tall tales is characterized by fictional, often intentionally ridiculous, stories that provide a reason for or origin of a natural phenomenon. Tall tales are often based on characters who are unusually adept or powerful; they are particularly appealing to children who are cognitively capable of understanding the tongue-in-cheek humor…

  13. Generation of TALE-Based Designer Epigenome Modifiers.

    PubMed

    Nitsch, Sandra; Mussolino, Claudio

    2018-01-01

    Manipulation of gene expression can be facilitated by editing the genome or the epigenome. Precise genome editing is traditionally achieved by using designer nucleases which are generally exploited to eliminate a specific gene product. Upon the introduction of a site-specific DNA double-strand break (DSB) by the nuclease, endogenous DSB repair mechanisms are in turn harnessed to induce DNA sequence changes that can result in target gene inactivation. Minimal off-target effects can be obtained by endowing designer nucleases with the highly specific DNA-binding domain (DBD) derived from transcription activator-like effectors (TALEs). In contrast, epigenome editing allows gene expression control without inducing changes in the DNA sequence by specifically altering epigenetic marks, as histone tails modifications or DNA methylation patterns within promoter or enhancer regions. Importantly, this approach allows both up- and downregulation of the target gene expression, and the effect is generally reversible. TALE-based designer epigenome modifiers combine the high specificity of TALE-derived DBDs with the power of epigenetic modifier domains to induce fast and long-lasting changes in the epigenetic landscape of a target gene and control its expression. Here we provide a detailed description for the generation of TALE-based designer epigenome modifiers and of a suitable reporter cell line to easily monitor their activity.

  14. TAL Performance and Mission Analysis in a CDL Capacitor Powered Direct-Drive Configuration

    NASA Technical Reports Server (NTRS)

    Hrbud, Ivana; Rose, M. Frank; Oleson, Steve R.; Jenkins, Rhonald M.

    1999-01-01

    The goals of this research are (1) to prove the concept feasibility of a direct-drive electric propulsion system, and (2) to evaluate the performance and characteristics of a Russian TAL (Thruster with Anode Layer) operating in a long-pulse mode, powered by a capacitor-based power source developed at Space Power Institute. The TAL, designated D-55, is characterized by an external acceleration zone and is powered by a unique chemical double layer (CDL) capacitor bank with a capacitance of 4 F at a charge voltage of 400 V. Performance testing of this power supply on the TAL was conducted at NASA Lewis Research Center in Cleveland, OH. Direct thrust measurements of the TAL were obtained at CDL power levels ranging from 450 to 1750 W. The specific impulse encompassed a range from 1150 s to 2200 s, yielding thruster system efficiencies between 50 and 60%. Preliminary mission analysis of the CDL direct-drive concept and other electric propulsion options was performed for the ORACLE spacecraft in 6am/6pm and 12am/12pm, 300 km sun-synchronous orbits. The direct-drive option was competitive with the other systems by increasing available net mass between 5 and 42% and reducing two-year system wet mass between 18 and 63%. Overall, the electric propulsion power requirements for the satellite solar array were reduced between 57 and 91% depending oil the orbit evaluated The direct-drive, CDL capacitor-based concept in electric propulsion thus promises to be a highly-efficient, viable alternative for satellite operations in specific near-Earth missions.

  15. A Fairy-Tale Landscape

    NASA Image and Video Library

    2008-05-29

    Fun, fairy-tale nicknames have been assigned to features in this animated view of the workspace reachable by the robotic arm of NASA Phoenix Mars Lander. For example, Sleepy Hollow denotes a trench and Headless designates a rock.

  16. Tales of Accreditation Woe.

    ERIC Educational Resources Information Center

    Dickmeyer, Nathan

    2002-01-01

    Offers cautionary tales depicting how an "Enron mentality" infiltrated three universities and jeopardized their accreditation status. The schools were guilty, respectively, of bad bookkeeping, lack of strategy and stable leadership, and loss of academic integrity by selling degrees. (EV)

  17. A Simple and Efficient Method for Assembling TALE Protein Based on Plasmid Library

    PubMed Central

    Xu, Huarong; Xin, Ying; Zhang, Tingting; Ma, Lixia; Wang, Xin; Chen, Zhilong; Zhang, Zhiying

    2013-01-01

    DNA binding domain of the transcription activator-like effectors (TALEs) from Xanthomonas sp. consists of tandem repeats that can be rearranged according to a simple cipher to target new DNA sequences with high DNA-binding specificity. This technology has been successfully applied in varieties of species for genome engineering. However, assembling long TALE tandem repeats remains a big challenge precluding wide use of this technology. Although several new methodologies for efficiently assembling TALE repeats have been recently reported, all of them require either sophisticated facilities or skilled technicians to carry them out. Here, we described a simple and efficient method for generating customized TALE nucleases (TALENs) and TALE transcription factors (TALE-TFs) based on TALE repeat tetramer library. A tetramer library consisting of 256 tetramers covers all possible combinations of 4 base pairs. A set of unique primers was designed for amplification of these tetramers. PCR products were assembled by one step of digestion/ligation reaction. 12 TALE constructs including 4 TALEN pairs targeted to mouse Gt(ROSA)26Sor gene and mouse Mstn gene sequences as well as 4 TALE-TF constructs targeted to mouse Oct4, c-Myc, Klf4 and Sox2 gene promoter sequences were generated by using our method. The construction routines took 3 days and parallel constructions were available. The rate of positive clones during colony PCR verification was 64% on average. Sequencing results suggested that all TALE constructs were performed with high successful rate. This is a rapid and cost-efficient method using the most common enzymes and facilities with a high success rate. PMID:23840477

  18. A simple and efficient method for assembling TALE protein based on plasmid library.

    PubMed

    Zhang, Zhiqiang; Li, Duo; Xu, Huarong; Xin, Ying; Zhang, Tingting; Ma, Lixia; Wang, Xin; Chen, Zhilong; Zhang, Zhiying

    2013-01-01

    DNA binding domain of the transcription activator-like effectors (TALEs) from Xanthomonas sp. consists of tandem repeats that can be rearranged according to a simple cipher to target new DNA sequences with high DNA-binding specificity. This technology has been successfully applied in varieties of species for genome engineering. However, assembling long TALE tandem repeats remains a big challenge precluding wide use of this technology. Although several new methodologies for efficiently assembling TALE repeats have been recently reported, all of them require either sophisticated facilities or skilled technicians to carry them out. Here, we described a simple and efficient method for generating customized TALE nucleases (TALENs) and TALE transcription factors (TALE-TFs) based on TALE repeat tetramer library. A tetramer library consisting of 256 tetramers covers all possible combinations of 4 base pairs. A set of unique primers was designed for amplification of these tetramers. PCR products were assembled by one step of digestion/ligation reaction. 12 TALE constructs including 4 TALEN pairs targeted to mouse Gt(ROSA)26Sor gene and mouse Mstn gene sequences as well as 4 TALE-TF constructs targeted to mouse Oct4, c-Myc, Klf4 and Sox2 gene promoter sequences were generated by using our method. The construction routines took 3 days and parallel constructions were available. The rate of positive clones during colony PCR verification was 64% on average. Sequencing results suggested that all TALE constructs were performed with high successful rate. This is a rapid and cost-efficient method using the most common enzymes and facilities with a high success rate.

  19. TALE-PvuII fusion proteins--novel tools for gene targeting.

    PubMed

    Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

    2013-01-01

    Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity.

  20. Comprehensive Interrogation of Natural TALE DNA Binding Modules and Transcriptional Repressor Domains

    PubMed Central

    Cong, Le; Zhou, Ruhong; Kuo, Yu-chi; Cunniff, Margaret; Zhang, Feng

    2012-01-01

    Transcription activator-like effectors (TALE) are sequence-specific DNA binding proteins that harbor modular, repetitive DNA binding domains. TALEs have enabled the creation of customizable designer transcriptional factors and sequence-specific nucleases for genome engineering. Here we report two improvements of the TALE toolbox for achieving efficient activation and repression of endogenous gene expression in mammalian cells. We show that the naturally occurring repeat variable diresidue (RVD) Asn-His (NH) has high biological activity and specificity for guanine, a highly prevalent base in mammalian genomes. We also report an effective TALE transcriptional repressor architecture for targeted inhibition of transcription in mammalian cells. These findings will improve the precision and effectiveness of genome engineering that can be achieved using TALEs. PMID:22828628

  1. OGS Maintenance

    NASA Image and Video Library

    2010-07-21

    ISS024-E-009246 (21 July 2010) --- NASA astronaut Tracy Caldwell Dyson, Expedition 24 flight engineer, is pictured during troubleshooting operations of the Oxygen Generator System (OGS) hardware and replacement of an H2 (hydrogen) Dome Orbit Replaceable Unit (ORU) in the Destiny laboratory of the International Space Station.

  2. Single molecule real-time sequencing of Xanthomonas oryzae genomes reveals a dynamic structure and complex TAL (transcription activator-like) effector gene relationships

    PubMed Central

    Booher, Nicholas J.; Carpenter, Sara C. D.; Sebra, Robert P.; Wang, Li; Salzberg, Steven L.; Leach, Jan E.

    2015-01-01

    Pathogen-injected, direct transcriptional activators of host genes, TAL (transcription activator-like) effectors play determinative roles in plant diseases caused by Xanthomonas spp. A large domain of nearly identical, 33–35 aa repeats in each protein mediates DNA recognition. This modularity makes TAL effectors customizable and thus important also in biotechnology. However, the repeats render TAL effector (tal) genes nearly impossible to assemble using next-generation, short reads. Here, we demonstrate that long-read, single molecule real-time (SMRT) sequencing solves this problem. Taking an ensemble approach to first generate local, tal gene contigs, we correctly assembled de novo the genomes of two strains of the rice pathogen X. oryzae completed previously using the Sanger method and even identified errors in those references. Sequencing two more strains revealed a dynamic genome structure and a striking plasticity in tal gene content. Our results pave the way for population-level studies to inform resistance breeding, improve biotechnology and probe TAL effector evolution. PMID:27148456

  3. What Makes a Fairy Tale Good: The Queer Kindness of "The Golden Bird."

    ERIC Educational Resources Information Center

    Nodelman, Perry M.

    1977-01-01

    Uses a literary analysis of "The Golden Bird," a Grimm Brothers fairy tale, to show how an investigation of the literary qualities of fairy tales can reveal what the artistry of such tales consists of. (GT)

  4. Ugiuvangmiut Quliapyuit = King Island Tales. Eskimo History and Legends from Bering Strait.

    ERIC Educational Resources Information Center

    Kaplan, Lawrence D., Ed.

    The collection of native tales from King Island, Alaska, contains tales told originally in Inupiaq Eskimo by seven native elders. Introductory sections provide background information on the storytellers, King Island Village and its people, traditional life there, and the language of the King Islanders. The 25 tales are divided into groups:…

  5. A transcription activator-like effector (TALE) induction system mediated by proteolysis.

    PubMed

    Copeland, Matthew F; Politz, Mark C; Johnson, Charles B; Markley, Andrew L; Pfleger, Brian F

    2016-04-01

    Simple and predictable trans-acting regulatory tools are needed in the fields of synthetic biology and metabolic engineering to build complex genetic circuits and optimize the levels of native and heterologous gene products. Transcription activator-like effectors (TALEs) are bacterial virulence factors that have recently gained traction in biotechnology applications owing to their customizable DNA-binding specificity. In this work we expanded the versatility of these transcription factors to create an inducible TALE system by inserting tobacco-etch virus (TEV) protease recognition sites into the TALE backbone. The resulting engineered TALEs maintain transcriptional repression of their target genes in Escherichia coli, but are degraded after induction of the TEV protease, thereby promoting expression of the previously repressed target gene of interest. This TALE-TEV technology enables both repression and induction of plasmid or chromosomal target genes in a manner analogous to traditional repressor proteins but with the added flexibility of being operator-agnostic.

  6. megaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering.

    PubMed

    Boissel, Sandrine; Jarjour, Jordan; Astrakhan, Alexander; Adey, Andrew; Gouble, Agnès; Duchateau, Philippe; Shendure, Jay; Stoddard, Barry L; Certo, Michael T; Baker, David; Scharenberg, Andrew M

    2014-02-01

    Rare-cleaving endonucleases have emerged as important tools for making targeted genome modifications. While multiple platforms are now available to generate reagents for research applications, each existing platform has significant limitations in one or more of three key properties necessary for therapeutic application: efficiency of cleavage at the desired target site, specificity of cleavage (i.e. rate of cleavage at 'off-target' sites), and efficient/facile means for delivery to desired target cells. Here, we describe the development of a single-chain rare-cleaving nuclease architecture, which we designate 'megaTAL', in which the DNA binding region of a transcription activator-like (TAL) effector is used to 'address' a site-specific meganuclease adjacent to a single desired genomic target site. This architecture allows the generation of extremely active and hyper-specific compact nucleases that are compatible with all current viral and nonviral cell delivery methods.

  7. E-Classical Fairy Tales: Multimedia Builder as a Tool

    ERIC Educational Resources Information Center

    Eteokleous, Nikleia; Ktoridou, Despo; Tsolakidis, Symeon

    2011-01-01

    The study examines pre-service teachers' experiences in delivering a traditional-classical fairy tale using the Multimedia Builder software, in other words an e-fairy tale. A case study approach was employed, collecting qualitative data through classroom observations and focus groups. The results focus on pre-service teachers' reactions, opinions,…

  8. Rapid and highly efficient construction of TALE-based transcriptional regulators and nucleases for genome modification.

    PubMed

    Li, Lixin; Piatek, Marek J; Atef, Ahmed; Piatek, Agnieszka; Wibowo, Anjar; Fang, Xiaoyun; Sabir, J S M; Zhu, Jian-Kang; Mahfouz, Magdy M

    2012-03-01

    Transcription activator-like effectors (TALEs) can be used as DNA-targeting modules by engineering their repeat domains to dictate user-selected sequence specificity. TALEs have been shown to function as site-specific transcriptional activators in a variety of cell types and organisms. TALE nucleases (TALENs), generated by fusing the FokI cleavage domain to TALE, have been used to create genomic double-strand breaks. The identity of the TALE repeat variable di-residues, their number, and their order dictate the DNA sequence specificity. Because TALE repeats are nearly identical, their assembly by cloning or even by synthesis is challenging and time consuming. Here, we report the development and use of a rapid and straightforward approach for the construction of designer TALE (dTALE) activators and nucleases with user-selected DNA target specificity. Using our plasmid set of 100 repeat modules, researchers can assemble repeat domains for any 14-nucleotide target sequence in one sequential restriction-ligation cloning step and in only 24 h. We generated several custom dTALEs and dTALENs with new target sequence specificities and validated their function by transient expression in tobacco leaves and in vitro DNA cleavage assays, respectively. Moreover, we developed a web tool, called idTALE, to facilitate the design of dTALENs and the identification of their genomic targets and potential off-targets in the genomes of several model species. Our dTALE repeat assembly approach along with the web tool idTALE will expedite genome-engineering applications in a variety of cell types and organisms including plants.

  9. Hydrocarbon-soluble low-melting corrosion inhibitor TAL-3

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

    Nesterenko, S.A.; Sorokin, V.I.; Naumenko, O.V.

    1987-03-01

    The inhibitor TAL-3 is intended for the corrosion protection of metals that come into contact with two-phase systems of the hydrocarbon-water type. It is applicable to the service conditions of equipment and pipelines of the petroleum and petroleum refining industries. The purpose of this paper was to electrochemically assess its solubility in such systems and its inhibitory properties on samples of 08kp steel toward the effects of refinery and oil field waste water and process emulsions both on the laboratory scale and in field tests.

  10. Tale of a Performance Contract

    ERIC Educational Resources Information Center

    Berson, Minnie Perrin

    1971-01-01

    Excerpts from Texarkana and Gary: A Tale of Two Performance Contracts," Childhood Education Magazine, March 1971; reports on observations made during visit to Gary, Indiana, school under contract to Behavioral Research Laboratories. (RT)

  11. Computational Drafting of Plot Structures for Russian Folk Tales.

    PubMed

    Gervás, Pablo

    The plots of stories are known to follow general patterns in terms of their overall structure. This was the basic tenet of structuralist approaches to narratology. Vladimir Propp proposed a procedure for the generation of new tales based on his semi-formal description of the structure of Russian folk tales. This is one of the first existing instances of a creative process described procedurally. The present paper revisits Propp's morphology to build a system that generates instances of Russian folk tales. Propp's view of the folk tale as a rigid sequence of character functions is employed as a plot driver, and some issues that Propp declared relevant but did not explore in detail-such as long-range dependencies between functions or the importance of endings-are given computational shape in the context of a broader architecture that captures all the aspects discussed by Propp. A set of simple evaluation metrics for the resulting outputs is defined inspired on Propp's formalism. The potential of the resulting system for providing a creative story generation system is discussed, and possible lines of future work are discussed.

  12. TALE activators regulate gene expression in a position- and strand-dependent manner in mammalian cells.

    PubMed

    Uhde-Stone, Claudia; Cheung, Edna; Lu, Biao

    2014-01-24

    Transcription activator-like effectors (TALEs) are a class of transcription factors that are readily programmable to regulate gene expression. Despite their growing popularity, little is known about binding site parameters that influence TALE-mediated gene activation in mammalian cells. We demonstrate that TALE activators modulate gene expression in mammalian cells in a position- and strand-dependent manner. To study the effects of binding site location, we engineered TALEs customized to recognize specific DNA sequences located in either the promoter or the transcribed region of reporter genes. We found that TALE activators robustly activated reporter genes when their binding sites were located within the promoter region. In contrast, TALE activators inhibited the expression of reporter genes when their binding sites were located on the sense strand of the transcribed region. Notably, this repression was independent of the effector domain utilized, suggesting a simple blockage mechanism. We conclude that TALE activators in mammalian cells regulate genes in a position- and strand-dependent manner that is substantially different from gene activation by native TALEs in plants. These findings have implications for optimizing the design of custom TALEs for genetic manipulation in mammalian cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. An engineered promoter driving expression of a microbial avirulence gene confers recognition of TAL effectors and reduces growth of diverse Xanthomonas strains in citrus.

    PubMed

    Shantharaj, Deepak; Römer, Patrick; Figueiredo, Jose F L; Minsavage, Gerald V; Krönauer, Christina; Stall, Robert E; Moore, Gloria A; Fisher, Latanya C; Hu, Yang; Horvath, Diana M; Lahaye, Thomas; Jones, Jeffrey B

    2017-09-01

    Xanthomonas citri ssp. citri (X. citri), causal agent of citrus canker, uses transcription activator-like effectors (TALEs) as major pathogenicity factors. TALEs, which are delivered into plant cells through the type III secretion system (T3SS), interact with effector binding elements (EBEs) in host genomes to activate the expression of downstream susceptibility genes to promote disease. Predictably, TALEs bind EBEs in host promoters via known combinations of TALE amino acids to DNA bases, known as the TALE code. We introduced 14 EBEs, matching distinct X. citri TALEs, into the promoter of the pepper Bs3 gene (ProBs3 1EBE ), and fused this engineered promoter with multiple EBEs (ProBs3 14EBE ) to either the β-glucuronidase (GUS) reporter gene or the coding sequence (cds) of the pepper gene, Bs3. TALE-induced expression of the Bs3 cds in citrus leaves resulted in no visible hypersensitive response (HR). Therefore, we utilized a different approach in which ProBs3 1EBE and ProBs3 14EBE were fused to the Xanthomonas gene, avrGf1, which encodes a bacterial effector that elicits an HR in grapefruit and sweet orange. We demonstrated, in transient assays, that activation of ProBs3 14EBE by X. citri TALEs is T3SS dependent, and that the expression of AvrGf1 triggers HR and correlates with reduced bacterial growth. We further demonstrated that all tested virulent X. citri strains from diverse geographical locations activate ProBs3 14EBE . TALEs are essential for the virulence of X. citri strains and, because the engineered promoter traps are activated by multiple TALEs, this concept has the potential to confer broad-spectrum, durable resistance to citrus canker in stably transformed plants. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  14. Resurrecting the buried self: fairy tales and the analytic encounter.

    PubMed

    Jacobs, Linda

    2011-12-01

    The author uses the lens of myth and fairy tales to examine the narratives generated by the analytic experience. Fairy tales are understood as representing fundamental developmental conflicts, accounting for their enduring power over time. The analytic encounter is seen as an analogue of the fairy tale in which the hidden self, damaged by loss and abandonment, reemerges only through the redemptive power of [an] other's love. Clinical material is presented in which hidden parts of the patient's self are projected into the analyst for safekeeping; these hidden parts resonate with the analyst's own lost, unrealized potential and form an intersubjective experience which the author believes is transformative. The patient's dormant powers emerge in a newly experienced atmosphere of recognition, and in this way, the analytic encounter resembles the fairy tale in providing an identificatory bond and a protective space for the patient's hidden vitality.

  15. Improved specificity of TALE-based genome editing using an expanded RVD repertoire.

    PubMed

    Miller, Jeffrey C; Zhang, Lei; Xia, Danny F; Campo, John J; Ankoudinova, Irina V; Guschin, Dmitry Y; Babiarz, Joshua E; Meng, Xiangdong; Hinkley, Sarah J; Lam, Stephen C; Paschon, David E; Vincent, Anna I; Dulay, Gladys P; Barlow, Kyle A; Shivak, David A; Leung, Elo; Kim, Jinwon D; Amora, Rainier; Urnov, Fyodor D; Gregory, Philip D; Rebar, Edward J

    2015-05-01

    Transcription activator-like effector (TALE) proteins have gained broad appeal as a platform for targeted DNA recognition, largely owing to their simple rules for design. These rules relate the base specified by a single TALE repeat to the identity of two key residues (the repeat variable diresidue, or RVD) and enable design for new sequence targets via modular shuffling of these units. A key limitation of these rules is that their simplicity precludes options for improving designs that are insufficiently active or specific. Here we address this limitation by developing an expanded set of RVDs and applying them to improve the performance of previously described TALEs. As an extreme example, total conversion of a TALE nuclease to new RVDs substantially reduced off-target cleavage in cellular studies. By providing new RVDs and design strategies, these studies establish options for developing improved TALEs for broader application across medicine and biotechnology.

  16. TALE-PvuII Fusion Proteins – Novel Tools for Gene Targeting

    PubMed Central

    Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

    2013-01-01

    Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity. PMID:24349308

  17. OGS Hydrogen Sensor ORU R&R

    NASA Image and Video Library

    2012-04-18

    ISS030-E-236919 (18 April 2012) --- NASA astronaut Dan Burbank, Expedition 30 commander, works with the Oxygen Generator System (OGS) rack in the Tranquility node of the International Space Station. Burbank unpowered the OGS, purged the hydrogen sensor Orbital Replacement Unit (ORU) with the Hydrogen Sensor ORU Purge Adapter (HOPA) for return to Earth, and replaced the hydrogen sensor with a new spare, then cleaned the rack Avionics Air Assembly (AAA).

  18. Writing and Retelling Multiple Ethnographic Tales of a Soup Kitchen for the Homeless.

    ERIC Educational Resources Information Center

    Miller, Dana L.; Creswell, John W.; Olander, Lisa

    An ethnographic study narrated three tales about a soup kitchen for the homeless and the near-homeless. To provide a cultural, ethnographic analysis, and share fieldwork experiences the study began with realist and confessional tales. These two tales emerged from the initial writing and presenting of the soup kitchen ethnography to qualitative…

  19. Fairy Tales as a Cultural Context in the French Classroom.

    ERIC Educational Resources Information Center

    Obergfell, Sandra C.

    1983-01-01

    Discusses the use of fairy tales in intermediate and advanced French courses as source material for discussion of French cultural values and traditional behavior patterns. Methods of analyzing values in a fairy tale and implementation in the classroom are discussed using "Le Petit Chaperon Rouge" as an example. (AMH)

  20. Dissection of TALE-dependent gene activation reveals that they induce transcription cooperatively and in both orientations

    PubMed Central

    Streubel, Jana; Baum, Heidi; Grau, Jan; Stuttman, Johannes; Boch, Jens

    2017-01-01

    Plant-pathogenic Xanthomonas bacteria inject transcription activator-like effector proteins (TALEs) into host cells to specifically induce transcription of plant genes and enhance susceptibility. Although the DNA-binding mode is well-understood it is still ambiguous how TALEs initiate transcription and whether additional promoter elements are needed to support this. To systematically dissect prerequisites for transcriptional initiation the activity of one TALE was compared on different synthetic Bs4 promoter fragments. In addition, a large collection of artificial TALEs spanning the OsSWEET14 promoter was compared. We show that the presence of a TALE alone is not sufficient to initiate transcription suggesting the requirement of additional supporting promoter elements. At the OsSWEET14 promoter TALEs can initiate transcription from various positions, in a synergistic manner of multiple TALEs binding in parallel to the promoter, and even by binding in reverse orientation. TALEs are known to shift the transcriptional start site, but our data show that this shift depends on the individual position of a TALE within a promoter context. Our results implicate that TALEs function like classical enhancer-binding proteins and initiate transcription in both orientations which has consequences for in planta target gene prediction and design of artificial activators. PMID:28301511

  1. Dissection of TALE-dependent gene activation reveals that they induce transcription cooperatively and in both orientations.

    PubMed

    Streubel, Jana; Baum, Heidi; Grau, Jan; Stuttman, Johannes; Boch, Jens

    2017-01-01

    Plant-pathogenic Xanthomonas bacteria inject transcription activator-like effector proteins (TALEs) into host cells to specifically induce transcription of plant genes and enhance susceptibility. Although the DNA-binding mode is well-understood it is still ambiguous how TALEs initiate transcription and whether additional promoter elements are needed to support this. To systematically dissect prerequisites for transcriptional initiation the activity of one TALE was compared on different synthetic Bs4 promoter fragments. In addition, a large collection of artificial TALEs spanning the OsSWEET14 promoter was compared. We show that the presence of a TALE alone is not sufficient to initiate transcription suggesting the requirement of additional supporting promoter elements. At the OsSWEET14 promoter TALEs can initiate transcription from various positions, in a synergistic manner of multiple TALEs binding in parallel to the promoter, and even by binding in reverse orientation. TALEs are known to shift the transcriptional start site, but our data show that this shift depends on the individual position of a TALE within a promoter context. Our results implicate that TALEs function like classical enhancer-binding proteins and initiate transcription in both orientations which has consequences for in planta target gene prediction and design of artificial activators.

  2. The TALE face of Hox proteins in animal evolution.

    PubMed

    Merabet, Samir; Galliot, Brigitte

    2015-01-01

    Hox genes are major regulators of embryonic development. One of their most conserved functions is to coordinate the formation of specific body structures along the anterior-posterior (AP) axis in Bilateria. This architectural role was at the basis of several morphological innovations across bilaterian evolution. In this review, we traced the origin of the Hox patterning system by considering the partnership with PBC and Meis proteins. PBC and Meis belong to the TALE-class of homeodomain-containing transcription factors and act as generic cofactors of Hox proteins for AP axis patterning in Bilateria. Recent data indicate that Hox proteins acquired the ability to interact with their TALE partners in the last common ancestor of Bilateria and Cnidaria. These interactions relied initially on a short peptide motif called hexapeptide (HX), which is present in Hox and non-Hox protein families. Remarkably, Hox proteins can also recruit the TALE cofactors by using specific PBC Interaction Motifs (SPIMs). We describe how a functional Hox/TALE patterning system emerged in eumetazoans through the acquisition of SPIMs. We anticipate that interaction flexibility could be found in other patterning systems, being at the heart of the astonishing morphological diversity observed in the animal kingdom.

  3. Libraries of Synthetic TALE-Activated Promoters: Methods and Applications.

    PubMed

    Schreiber, T; Tissier, A

    2016-01-01

    The discovery of proteins with programmable DNA-binding specificities triggered a whole array of applications in synthetic biology, including genome editing, regulation of transcription, and epigenetic modifications. Among those, transcription activator-like effectors (TALEs) due to their natural function as transcription regulators, are especially well-suited for the development of orthogonal systems for the control of gene expression. We describe here the construction and testing of libraries of synthetic TALE-activated promoters which are under the control of a single TALE with a given DNA-binding specificity. These libraries consist of a fixed DNA-binding element for the TALE, a TATA box, and variable sequences of 19 bases upstream and 43 bases downstream of the DNA-binding element. These libraries were cloned using a Golden Gate cloning strategy making them usable as standard parts in a modular cloning system. The broad range of promoter activities detected and the versatility of these promoter libraries make them valuable tools for applications in the fine-tuning of expression in metabolic engineering projects or in the design and implementation of regulatory circuits. © 2016 Elsevier Inc. All rights reserved.

  4. TALE factors use two distinct functional modes to control an essential zebrafish gene expression program.

    PubMed

    Ladam, Franck; Stanney, William; Donaldson, Ian J; Yildiz, Ozge; Bobola, Nicoletta; Sagerström, Charles G

    2018-06-18

    TALE factors are broadly expressed embryonically and known to function in complexes with transcription factors (TFs) like Hox proteins at gastrula/segmentation stages, but it is unclear if such generally expressed factors act by the same mechanism throughout embryogenesis. We identify a TALE-dependent gene regulatory network (GRN) required for anterior development and detect TALE occupancy associated with this GRN throughout embryogenesis. At blastula stages, we uncover a novel functional mode for TALE factors, where they occupy genomic DECA motifs with nearby NF-Y sites. We demonstrate that TALE and NF-Y form complexes and regulate chromatin state at genes of this GRN. At segmentation stages, GRN-associated TALE occupancy expands to include HEXA motifs near PBX:HOX sites. Hence, TALE factors control a key GRN, but utilize distinct DNA motifs and protein partners at different stages - a strategy that may also explain their oncogenic potential and may be employed by other broadly expressed TFs. © 2018, Ladam et al.

  5. Fairy-tale planet: creative science writing for children

    NASA Astrophysics Data System (ADS)

    Lanza, Tiziana; D'Addezio, Giuliana

    2017-04-01

    During public events organized by our Institute sometimes we have predisposed a corner to entertain primary school children with fairy-tales about the planet. In that occasion we realized that even if children could take part in other activities more in fashion such as laboratories, theatre performances, exhibits, they were very attracted by fairy tales, such an "ancient" tradition. This year within the projects "alternanza scuola-lavoro" we are planning to involve also the students of the secondary schools to learn themselves how to animate a fairy-tale corner for children. The "alternanza scuola lavoro" (interchange school/work) has been recently introduced in the Italian school as a methodology for implementing the second cycle teaching. The general purpose is to ensure that 15 to 18 years old students, beside the access to basic knowledge, can acquire skills in the employment and real work environments experiencing other teaching methods based both on knowledge and know-how. We will then start a new adventure by investigating what will be the best way to introduce children to creative science writing for the planet. The aim would be that of creating a format suitable for children either for writing all together a planet fairy-tale in class, or individually. The final goal is to raise awareness about the environmental problems by stimulating in scholars their own creativity.

  6. Programmable DNA-binding proteins from Burkholderia provide a fresh perspective on the TALE-like repeat domain

    PubMed Central

    de Lange, Orlando; Wolf, Christina; Dietze, Jörn; Elsaesser, Janett; Morbitzer, Robert; Lahaye, Thomas

    2014-01-01

    The tandem repeats of transcription activator like effectors (TALEs) mediate sequence-specific DNA binding using a simple code. Naturally, TALEs are injected by Xanthomonas bacteria into plant cells to manipulate the host transcriptome. In the laboratory TALE DNA binding domains are reprogrammed and used to target a fused functional domain to a genomic locus of choice. Research into the natural diversity of TALE-like proteins may provide resources for the further improvement of current TALE technology. Here we describe TALE-like proteins from the endosymbiotic bacterium Burkholderia rhizoxinica, termed Bat proteins. Bat repeat domains mediate sequence-specific DNA binding with the same code as TALEs, despite less than 40% sequence identity. We show that Bat proteins can be adapted for use as transcription factors and nucleases and that sequence preferences can be reprogrammed. Unlike TALEs, the core repeats of each Bat protein are highly polymorphic. This feature allowed us to explore alternative strategies for the design of custom Bat repeat arrays, providing novel insights into the functional relevance of non-RVD residues. The Bat proteins offer fertile grounds for research into the creation of improved programmable DNA-binding proteins and comparative insights into TALE-like evolution. PMID:24792163

  7. Normativity in Fairy Tales: Scope, Range and Modes of Communication

    ERIC Educational Resources Information Center

    Hohr, Hansjörg

    2013-01-01

    The article studies in three steps how the fairy tale articulates its normative content and what the educational consequence of this kind of communication is. First, the articulation of normativity in fictional literature in general is discussed. Second, the specific mode in which the fairy tale articulates its normativity is studied according to…

  8. Live visualization of genomic loci with BiFC-TALE

    PubMed Central

    Hu, Huan; Zhang, Hongmin; Wang, Sheng; Ding, Miao; An, Hui; Hou, Yingping; Yang, Xiaojing; Wei, Wensheng; Sun, Yujie; Tang, Chao

    2017-01-01

    Tracking the dynamics of genomic loci is important for understanding the mechanisms of fundamental intracellular processes. However, fluorescent labeling and imaging of such loci in live cells have been challenging. One of the major reasons is the low signal-to-background ratio (SBR) of images mainly caused by the background fluorescence from diffuse full-length fluorescent proteins (FPs) in the living nucleus, hampering the application of live cell genomic labeling methods. Here, combining bimolecular fluorescence complementation (BiFC) and transcription activator-like effector (TALE) technologies, we developed a novel method for labeling genomic loci (BiFC-TALE), which largely reduces the background fluorescence level. Using BiFC-TALE, we demonstrated a significantly improved SBR by imaging telomeres and centromeres in living cells in comparison with the methods using full-length FP. PMID:28074901

  9. Live visualization of genomic loci with BiFC-TALE.

    PubMed

    Hu, Huan; Zhang, Hongmin; Wang, Sheng; Ding, Miao; An, Hui; Hou, Yingping; Yang, Xiaojing; Wei, Wensheng; Sun, Yujie; Tang, Chao

    2017-01-11

    Tracking the dynamics of genomic loci is important for understanding the mechanisms of fundamental intracellular processes. However, fluorescent labeling and imaging of such loci in live cells have been challenging. One of the major reasons is the low signal-to-background ratio (SBR) of images mainly caused by the background fluorescence from diffuse full-length fluorescent proteins (FPs) in the living nucleus, hampering the application of live cell genomic labeling methods. Here, combining bimolecular fluorescence complementation (BiFC) and transcription activator-like effector (TALE) technologies, we developed a novel method for labeling genomic loci (BiFC-TALE), which largely reduces the background fluorescence level. Using BiFC-TALE, we demonstrated a significantly improved SBR by imaging telomeres and centromeres in living cells in comparison with the methods using full-length FP.

  10. [The Impact of Electronic Monitoring on Healthcare Associated Infections: The Role of the HViTAL Platform].

    PubMed

    Oliveira, Rita Fontes; Castro, Lídia; Almeida, José Pedro; Alves, Carlos; Ferreira, António

    2016-11-01

    In Portugal, 9.8% of patients admitted were inflicted with healthcare associated infections, corresponding to a prevalence of 11.7%. The Hospital de São João has developed a business intelligence platform able to supervise (the patients), monitor (the clinical condition) and notify (the healthcare personnel): HViTAL. This study aims to assess the impact of electronic monitoring on healthcare associated infections since the year of HViTAL implementation. We evaluated data since January 2008 (moment from which computerized records exist) until December 2011, comparing them with subsequent data, those corresponding to January 2012 (implementation date of HViTAL) until 19 October 2015. There was an upward trend of infection parameters in the 2008 - 2011 period. Since January 2012 and October 2015, all parameters of the infection indicator showed a negative linear trend. The results are very suggestive that the HVITAL may have had an impact on improving parameters associated to healthcare associated infections. Basic measures of infection control were highlighted since 2005, with an increasing number of health professional awareness campaigns, a fact which, although not analyzed in this report, may also have contributed to the observed improvement. Our study did not include other variables such as investment in human capital. There was a clear improvement in all areas characterizing the healthcare associated infections, with obvious positive impact with the introduction of HViTAL.

  11. The Indecisive Feminist: Study of Anne Sexton's Revisionist Fairy Tales

    ERIC Educational Resources Information Center

    Mohammed, Nadia Fayidh

    2015-01-01

    Fairy tales to female writers are major resource for their abundant writings, but for the feminist poets since 1960s, they become essential subject matter to often deal with in their literary production. With the motivation to address the conventional tradition of patriarchal society, and re-address the stereotype females inhabiting these tales,…

  12. Fairy Tales of the Sea [and] A Guide for Teachers.

    ERIC Educational Resources Information Center

    Cowan, Elizabeth, Comp.; And Others

    Presented are 25 fairy tales from around the world that are related to the sea. Included in the teacher's guide are activities designed to serve as a catalyst to stimulate varied classroom uses for the tales. The curriculum outline provided follows the English Language Arts Curriculum Framework suggested by the Texas Education Agency and covers…

  13. The Fantastic Tale for Children: Its Literary and Educational Problems.

    ERIC Educational Resources Information Center

    Klingberg, Goete

    1967-01-01

    The fantastic tale is a genre of children's literature in which magic and reality are found side by side in a superficially plausible story with a definite historical setting. Motifs characteristic of the tale are living toys, strange children, modern witches, space and time displacements, "doors" to the wonderland, the mythical world itself, and…

  14. Two- and three-input TALE-based AND logic computation in embryonic stem cells.

    PubMed

    Lienert, Florian; Torella, Joseph P; Chen, Jan-Hung; Norsworthy, Michael; Richardson, Ryan R; Silver, Pamela A

    2013-11-01

    Biological computing circuits can enhance our ability to control cellular functions and have potential applications in tissue engineering and medical treatments. Transcriptional activator-like effectors (TALEs) represent attractive components of synthetic gene regulatory circuits, as they can be designed de novo to target a given DNA sequence. We here demonstrate that TALEs can perform Boolean logic computation in mammalian cells. Using a split-intein protein-splicing strategy, we show that a functional TALE can be reconstituted from two inactive parts, thus generating two-input AND logic computation. We further demonstrate three-piece intein splicing in mammalian cells and use it to perform three-input AND computation. Using methods for random as well as targeted insertion of these relatively large genetic circuits, we show that TALE-based logic circuits are functional when integrated into the genome of mouse embryonic stem cells. Comparing construct variants in the same genomic context, we modulated the strength of the TALE-responsive promoter to improve the output of these circuits. Our work establishes split TALEs as a tool for building logic computation with the potential of controlling expression of endogenous genes or transgenes in response to a combination of cellular signals.

  15. TALE transcription factors during early development of the vertebrate brain and eye.

    PubMed

    Schulte, Dorothea; Frank, Dale

    2014-01-01

    Our brain's cognitive performance arises from the coordinated activities of billions of nerve cells. Despite a high degree of morphological and functional differences, all neurons of the vertebrate central nervous system (CNS) arise from a common field of multipotent progenitors. Cell fate specification and differentiation are directed by multistep processes that include inductive/external cues, such as the extracellular matrix or growth factors, and cell-intrinsic determinants, such as transcription factors and epigenetic modulators of proteins and DNA. Here we review recent findings implicating TALE-homeodomain proteins in these processes. Although originally identified as HOX-cofactors, TALE proteins also contribute to many physiological processes that do not require HOX-activity. Particular focus is, therefore, given to HOX-dependent and -independent functions of TALE proteins during early vertebrate brain development. Additionally, we provide an overview about known upstream and downstream factors of TALE proteins in the developing vertebrate brain and discuss general concepts of how TALE proteins function to modulate neuronal cell fate specification. Copyright © 2013 Wiley Periodicals, Inc.

  16. Programmable DNA-binding proteins from Burkholderia provide a fresh perspective on the TALE-like repeat domain.

    PubMed

    de Lange, Orlando; Wolf, Christina; Dietze, Jörn; Elsaesser, Janett; Morbitzer, Robert; Lahaye, Thomas

    2014-06-01

    The tandem repeats of transcription activator like effectors (TALEs) mediate sequence-specific DNA binding using a simple code. Naturally, TALEs are injected by Xanthomonas bacteria into plant cells to manipulate the host transcriptome. In the laboratory TALE DNA binding domains are reprogrammed and used to target a fused functional domain to a genomic locus of choice. Research into the natural diversity of TALE-like proteins may provide resources for the further improvement of current TALE technology. Here we describe TALE-like proteins from the endosymbiotic bacterium Burkholderia rhizoxinica, termed Bat proteins. Bat repeat domains mediate sequence-specific DNA binding with the same code as TALEs, despite less than 40% sequence identity. We show that Bat proteins can be adapted for use as transcription factors and nucleases and that sequence preferences can be reprogrammed. Unlike TALEs, the core repeats of each Bat protein are highly polymorphic. This feature allowed us to explore alternative strategies for the design of custom Bat repeat arrays, providing novel insights into the functional relevance of non-RVD residues. The Bat proteins offer fertile grounds for research into the creation of improved programmable DNA-binding proteins and comparative insights into TALE-like evolution. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Using Fairy Tales to Change Perceptions of Self and Others.

    ERIC Educational Resources Information Center

    Gornicki, Sylvia B.

    Fairy tales can be used in the classroom to promote normal growth and development as well as carry a message of hope and faith in the strength and goodness of humans. Because fairy tales are imaginative literature, readers can safely experience and work through scary situations which are analogous to situations in real life. Bibliotherapy refers…

  18. Fairy Tales and Foreign Languages: Ever the Twain Shall Meet

    ERIC Educational Resources Information Center

    Davidheiser, James C.

    2007-01-01

    Fairy tales are not new to foreign language instructors, but on occasion they have been considered wither exoteric or unworthy of class time. Yet today there is a resurgence of interest in fairy tales and a rebirth of their use in the arts, which may serve foreign language instructors. This article presents historical background to inform…

  19. The TALE face of Hox proteins in animal evolution

    PubMed Central

    Merabet, Samir; Galliot, Brigitte

    2015-01-01

    Hox genes are major regulators of embryonic development. One of their most conserved functions is to coordinate the formation of specific body structures along the anterior-posterior (AP) axis in Bilateria. This architectural role was at the basis of several morphological innovations across bilaterian evolution. In this review, we traced the origin of the Hox patterning system by considering the partnership with PBC and Meis proteins. PBC and Meis belong to the TALE-class of homeodomain-containing transcription factors and act as generic cofactors of Hox proteins for AP axis patterning in Bilateria. Recent data indicate that Hox proteins acquired the ability to interact with their TALE partners in the last common ancestor of Bilateria and Cnidaria. These interactions relied initially on a short peptide motif called hexapeptide (HX), which is present in Hox and non-Hox protein families. Remarkably, Hox proteins can also recruit the TALE cofactors by using specific PBC Interaction Motifs (SPIMs). We describe how a functional Hox/TALE patterning system emerged in eumetazoans through the acquisition of SPIMs. We anticipate that interaction flexibility could be found in other patterning systems, being at the heart of the astonishing morphological diversity observed in the animal kingdom. PMID:26347770

  20. Genome Editing in Rats Using TALE Nucleases.

    PubMed

    Tesson, Laurent; Remy, Séverine; Ménoret, Séverine; Usal, Claire; Thinard, Reynald; Savignard, Chloé; De Cian, Anne; Giovannangeli, Carine; Concordet, Jean-Paul; Anegon, Ignacio

    2016-01-01

    The rat is an important animal model to understand gene function and model human diseases. Since recent years, the development of gene-specific nucleases has become important for generating new rat models of human diseases, to analyze the role of genes and to generate human antibodies. Transcription activator-like (TALE) nucleases efficiently create gene-specific knockout rats and lead to the possibility of gene targeting by homology-directed recombination (HDR) and generating knock-in rats. We describe a detailed protocol for generating knockout and knock-in rats via microinjection of TALE nucleases into fertilized eggs. This technology is an efficient, cost- and time-effective method for creating new rat models.

  1. Visualization of aging-associated chromatin alterations with an engineered TALE system

    PubMed Central

    Ren, Ruotong; Deng, Liping; Xue, Yanhong; Suzuki, Keiichiro; Zhang, Weiqi; Yu, Yang; Wu, Jun; Sun, Liang; Gong, Xiaojun; Luan, Huiqin; Yang, Fan; Ju, Zhenyu; Ren, Xiaoqing; Wang, Si; Tang, Hong; Geng, Lingling; Zhang, Weizhou; Li, Jian; Qiao, Jie; Xu, Tao; Qu, Jing; Liu, Guang-Hui

    2017-01-01

    Visualization of specific genomic loci in live cells is a prerequisite for the investigation of dynamic changes in chromatin architecture during diverse biological processes, such as cellular aging. However, current precision genomic imaging methods are hampered by the lack of fluorescent probes with high specificity and signal-to-noise contrast. We find that conventional transcription activator-like effectors (TALEs) tend to form protein aggregates, thereby compromising their performance in imaging applications. Through screening, we found that fusing thioredoxin with TALEs prevented aggregate formation, unlocking the full power of TALE-based genomic imaging. Using thioredoxin-fused TALEs (TTALEs), we achieved high-quality imaging at various genomic loci and observed aging-associated (epi) genomic alterations at telomeres and centromeres in human and mouse premature aging models. Importantly, we identified attrition of ribosomal DNA repeats as a molecular marker for human aging. Our study establishes a simple and robust imaging method for precisely monitoring chromatin dynamics in vitro and in vivo. PMID:28139645

  2. Molecular insights into the origin of the Hox-TALE patterning system

    PubMed Central

    Hudry, Bruno; Thomas-Chollier, Morgane; Volovik, Yael; Duffraisse, Marilyne; Dard, Amélie; Frank, Dale; Technau, Ulrich; Merabet, Samir

    2014-01-01

    Despite tremendous body form diversity in nature, bilaterian animals share common sets of developmental genes that display conserved expression patterns in the embryo. Among them are the Hox genes, which define different identities along the anterior–posterior axis. Hox proteins exert their function by interaction with TALE transcription factors. Hox and TALE members are also present in some but not all non-bilaterian phyla, raising the question of how Hox–TALE interactions evolved to provide positional information. By using proteins from unicellular and multicellular lineages, we showed that these networks emerged from an ancestral generic motif present in Hox and other related protein families. Interestingly, Hox-TALE networks experienced additional and extensive molecular innovations that were likely crucial for differentiating Hox functions along body plans. Together our results highlight how homeobox gene families evolved during eukaryote evolution to eventually constitute a major patterning system in Eumetazoans. DOI: http://dx.doi.org/10.7554/eLife.01939.001 PMID:24642410

  3. Molecular insights into the origin of the Hox-TALE patterning system.

    PubMed

    Hudry, Bruno; Thomas-Chollier, Morgane; Volovik, Yael; Duffraisse, Marilyne; Dard, Amélie; Frank, Dale; Technau, Ulrich; Merabet, Samir

    2014-03-18

    Despite tremendous body form diversity in nature, bilaterian animals share common sets of developmental genes that display conserved expression patterns in the embryo. Among them are the Hox genes, which define different identities along the anterior-posterior axis. Hox proteins exert their function by interaction with TALE transcription factors. Hox and TALE members are also present in some but not all non-bilaterian phyla, raising the question of how Hox-TALE interactions evolved to provide positional information. By using proteins from unicellular and multicellular lineages, we showed that these networks emerged from an ancestral generic motif present in Hox and other related protein families. Interestingly, Hox-TALE networks experienced additional and extensive molecular innovations that were likely crucial for differentiating Hox functions along body plans. Together our results highlight how homeobox gene families evolved during eukaryote evolution to eventually constitute a major patterning system in Eumetazoans. DOI: http://dx.doi.org/10.7554/eLife.01939.001.

  4. Spatial organization of heterologous metabolic system in vivo based on TALE.

    PubMed

    Zhu, Lv-yun; Qiu, Xin-Yuan; Zhu, Ling-Yun; Wu, Xiao-Min; Zhang, Yuan; Zhu, Qian-Hui; Fan, Dong-Yu; Zhu, Chu-Shu; Zhang, Dong-Yi

    2016-05-17

    For years, prokaryotic hosts have been widely applied in bio-engineering. However, the confined in vivo enzyme clustering of heterologous metabolic pathways in these organisms often results in low local concentrations of enzymes and substrates, leading to a low productive efficacy. We developed a new method to accelerate a heterologous metabolic system by integrating a transcription activator-like effector (TALE)-based scaffold system into an Escherichia coli chassis. The binding abilities of the TALEs to the artificial DNA scaffold were measured through ChIP-PCR. The effect of the system was determined through a split GFP study and validated through the heterologous production of indole-3-acetic acid (IAA) by incorporating TALE-fused IAA biosynthetic enzymes in E. coli. To the best of our knowledge, we are the first to use the TALE system as a scaffold for the spatial organization of bacterial metabolism. This technique might be used to establish multi-enzymatic reaction programs in a prokaryotic chassis for various applications.

  5. Identification of putative TAL effector targets of the citrus canker pathogens shows functional convergence underlying disease development and defense response

    PubMed Central

    2014-01-01

    Background Transcriptional activator-like (TAL) effectors, formerly known as the AvrBs3/PthA protein family, are DNA-binding effectors broadly found in Xanthomonas spp. that transactivate host genes upon injection via the bacterial type three-secretion system. Biologically relevant targets of TAL effectors, i.e. host genes whose induction is vital to establish a compatible interaction, have been reported for xanthomonads that colonize rice and pepper; however, citrus genes modulated by the TAL effectors PthA“s” and PthC“s” of the citrus canker bacteria Xanthomonas citri (Xc) and Xanthomonas aurantifolii pathotype C (XaC), respectively, are poorly characterized. Of particular interest, XaC causes canker disease in its host lemon (Citrus aurantifolia), but triggers a defense response in sweet orange. Results Based on, 1) the TAL effector-DNA binding code, 2) gene expression data of Xc and XaC-infiltrated sweet orange leaves, and 3) citrus hypocotyls transformed with PthA2, PthA4 or PthC1, we have identified a collection of Citrus sinensis genes potentially targeted by Xc and XaC TAL effectors. Our results suggest that similar with other strains of Xanthomonas TAL effectors, PthA2 and PthA4, and PthC1 to some extent, functionally converge. In particular, towards induction of genes involved in the auxin and gibberellin synthesis and response, cell division, and defense response. We also present evidence indicating that the TAL effectors act as transcriptional repressors and that the best scoring predicted DNA targets of PthA“s” and PthC“s” in citrus promoters predominantly overlap with or localize near to TATA boxes of core promoters, supporting the idea that TAL effectors interact with the host basal transcriptional machinery to recruit the RNA pol II and start transcription. Conclusions The identification of PthA“s” and PthC“s” targets, such as the LOB (LATERAL ORGAN BOUNDARY) and CCNBS genes that we report here, is key for the understanding

  6. Identification of putative TAL effector targets of the citrus canker pathogens shows functional convergence underlying disease development and defense response.

    PubMed

    Pereira, Andre L A; Carazzolle, Marcelo F; Abe, Valeria Y; de Oliveira, Maria L P; Domingues, Mariane N; Silva, Jaqueline C; Cernadas, Raul A; Benedetti, Celso E

    2014-02-25

    Transcriptional activator-like (TAL) effectors, formerly known as the AvrBs3/PthA protein family, are DNA-binding effectors broadly found in Xanthomonas spp. that transactivate host genes upon injection via the bacterial type three-secretion system. Biologically relevant targets of TAL effectors, i.e. host genes whose induction is vital to establish a compatible interaction, have been reported for xanthomonads that colonize rice and pepper; however, citrus genes modulated by the TAL effectors PthA"s" and PthC"s" of the citrus canker bacteria Xanthomonas citri (Xc) and Xanthomonas aurantifolii pathotype C (XaC), respectively, are poorly characterized. Of particular interest, XaC causes canker disease in its host lemon (Citrus aurantifolia), but triggers a defense response in sweet orange. Based on, 1) the TAL effector-DNA binding code, 2) gene expression data of Xc and XaC-infiltrated sweet orange leaves, and 3) citrus hypocotyls transformed with PthA2, PthA4 or PthC1, we have identified a collection of Citrus sinensis genes potentially targeted by Xc and XaC TAL effectors. Our results suggest that similar with other strains of Xanthomonas TAL effectors, PthA2 and PthA4, and PthC1 to some extent, functionally converge. In particular, towards induction of genes involved in the auxin and gibberellin synthesis and response, cell division, and defense response. We also present evidence indicating that the TAL effectors act as transcriptional repressors and that the best scoring predicted DNA targets of PthA"s" and PthC"s" in citrus promoters predominantly overlap with or localize near to TATA boxes of core promoters, supporting the idea that TAL effectors interact with the host basal transcriptional machinery to recruit the RNA pol II and start transcription. The identification of PthA"s" and PthC"s" targets, such as the LOB (lateral organ boundary) and CCNBS genes that we report here, is key for the understanding of the canker symptoms development during host

  7. Creative Thinking with Fairy Tales.

    ERIC Educational Resources Information Center

    Flack, Jerry

    2001-01-01

    This article discusses how creative thinking can be encouraged in students through such classic tools as brainstorming and the productive thinking elements of fluency, flexibility, originality, and elaboration. It describes how fairy tales can be used to foster these thinking skills and suggests classroom activities. (Contains two references.) (CR)

  8. The hematopoietic regulator TAL1 is required for chromatin looping between the β-globin LCR and human γ-globin genes to activate transcription.

    PubMed

    Yun, Won Ju; Kim, Yea Woon; Kang, Yujin; Lee, Jungbae; Dean, Ann; Kim, AeRi

    2014-04-01

    TAL1 is a key hematopoietic transcription factor that binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. The complex mediates long-range interaction between the β-globin locus control region (LCR) and active globin genes, and although TAL1 is one of the two DNA-binding complex members, its role is unclear. To explore the role of TAL1 in transcription activation of the human γ-globin genes, we reduced the expression of TAL1 in erythroid K562 cells using lentiviral short hairpin RNA, compromising its association in the β-globin locus. In the TAL1 knockdown cells, the γ-globin transcription was reduced to 35% and chromatin looping of the (G)γ-globin gene with the LCR was disrupted with decreased occupancy of the complex member Ldb1 and LMO2 in the locus. However, GATA-1 binding, DNase I hypersensitive site formation and several histone modifications were largely maintained across the β-globin locus. In addition, overexpression of TAL1 increased the γ-globin transcription and increased interaction frequency between the (G)γ-globin gene and LCR. These results indicate that TAL1 plays a critical role in chromatin loop formation between the γ-globin genes and LCR, which is a critical step for the transcription of the γ-globin genes.

  9. The hematopoietic regulator TAL1 is required for chromatin looping between the β-globin LCR and human γ-globin genes to activate transcription

    PubMed Central

    Yun, Won Ju; Kim, Yea Woon; Kang, Yujin; Lee, Jungbae; Dean, Ann; Kim, AeRi

    2014-01-01

    TAL1 is a key hematopoietic transcription factor that binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. The complex mediates long-range interaction between the β-globin locus control region (LCR) and active globin genes, and although TAL1 is one of the two DNA-binding complex members, its role is unclear. To explore the role of TAL1 in transcription activation of the human γ-globin genes, we reduced the expression of TAL1 in erythroid K562 cells using lentiviral short hairpin RNA, compromising its association in the β-globin locus. In the TAL1 knockdown cells, the γ-globin transcription was reduced to 35% and chromatin looping of the Gγ-globin gene with the LCR was disrupted with decreased occupancy of the complex member Ldb1 and LMO2 in the locus. However, GATA-1 binding, DNase I hypersensitive site formation and several histone modifications were largely maintained across the β-globin locus. In addition, overexpression of TAL1 increased the γ-globin transcription and increased interaction frequency between the Gγ-globin gene and LCR. These results indicate that TAL1 plays a critical role in chromatin loop formation between the γ-globin genes and LCR, which is a critical step for the transcription of the γ-globin genes. PMID:24470145

  10. LMO2 is required for TAL1 DNA binding activity and initiation of definitive haematopoiesis at the haemangioblast stage.

    PubMed

    Stanulovic, Vesna S; Cauchy, Pierre; Assi, Salam A; Hoogenkamp, Maarten

    2017-09-29

    LMO2 is a bridging factor within a DNA binding complex and is required for definitive haematopoiesis to occur. The developmental stage of the block in haematopoietic specification is not known. We show that Lmo2-/- mouse embryonic stem cells differentiated to Flk-1+ haemangioblasts, but less efficiently to haemogenic endothelium, which only produced primitive haematopoietic progenitors. Genome-wide approaches indicated that LMO2 is required at the haemangioblast stage to position the TAL1/LMO2/LDB1 complex to regulatory elements that are important for the establishment of the haematopoietic developmental program. In the absence of LMO2, the target site recognition of TAL1 is impaired. The lack of LMO2 resulted in altered gene expression levels already at the haemangioblast stage, with transcription factor genes accounting for ∼15% of affected genes. Comparison of Lmo2-/- with Tal1-/- Flk-1+ cells further showed that TAL1 was required to initiate or sustain Lmo2 expression. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Tell Me a Fairy Tale: A Parent's Guide to Telling Magical and Mythical Stories.

    ERIC Educational Resources Information Center

    Adler, Bill, Jr.

    Designed to help parents tell and retell their children's favorite fairy tales and stories, this collection condenses dozens of plots and lists characters, so that the parent can make a tale as long or as short as a sleepy child needs, personalize the story, and convey the true wonder of the originals through the spoken voice. The 64 tales in the…

  12. The Celebration of Death: Two Folk Tales about DEath. Mini-Module.

    ERIC Educational Resources Information Center

    African-American Inst., New York, NY. School Services Div.

    This module contains two African folk tales about death, two descriptions of African funerals, a lesson plan with 11 questions exploring the finality of and customs surrounding death, and a bibliography of five books which deal with African religious beliefs. The folk tales present concepts of death and immortality of the soul. The descriptions of…

  13. Targeted repression of AXIN2 and MYC gene expression using designer TALEs

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

    Rennoll, Sherri A.; Scott, Samantha A.; Yochum, Gregory S., E-mail: gsy3@psu.edu

    Highlights: • We designed TALE–SID fusion proteins to target AXIN2 and MYC. • TALE–SIDs bound the chromosomal AXIN2 and MYC genes and repressed their expression. • TALE–SIDs repress β-catenin{sup S45F}-dependent AXIN2 and MYC transcription. - Abstract: Designer TALEs (dTALEs) are chimeric transcription factors that can be engineered to regulate gene expression in mammalian cells. Whether dTALEs can block gene transcription downstream of signal transduction cascades, however, has yet to be fully explored. Here we tested whether dTALEs can be used to target genes whose expression is controlled by Wnt/β-catenin signaling. TALE DNA binding domains were engineered to recognize sequences adjacentmore » to Wnt responsive enhancer elements (WREs) that control expression of axis inhibition protein 2 (AXIN2) and c-MYC (MYC). These custom DNA binding domains were linked to the mSin3A interaction domain (SID) to generate TALE–SID chimeric repressors. The TALE–SIDs repressed luciferase reporter activity, bound their genomic target sites, and repressed AXIN2 and MYC expression in HEK293 cells. We generated a novel HEK293 cell line to determine whether the TALE–SIDs could function downstream of oncogenic Wnt/β-catenin signaling. Treating these cells with doxycycline and tamoxifen stimulates nuclear accumulation of a stabilized form of β-catenin found in a subset of colorectal cancers. The TALE–SIDs repressed AXIN2 and MYC expression in these cells, which suggests that dTALEs could offer an effective therapeutic strategy for the treatment of colorectal cancer.« less

  14. Potential for reducing the numbers of SiPM readout surfaces of laser-processed X'tal cube PET detectors.

    PubMed

    Hirano, Yoshiyuki; Inadama, Naoko; Yoshida, Eiji; Nishikido, Fumihiko; Murayama, Hideo; Watanabe, Mitsuo; Yamaya, Taiga

    2013-03-07

    We are developing a three-dimensional (3D) position-sensitive detector with isotropic spatial resolution, the X'tal cube. Originally, our design consisted of a crystal block for which all six surfaces were covered with arrays of multi-pixel photon counters (MPPCs). In this paper, we examined the feasibility of reducing the number of surfaces on which a MPPC array must be connected with the aim of reducing the complexity of the system. We evaluated two kinds of laser-processed X'tal cubes of 3 mm and 2 mm pitch segments while varying the numbers of the 4 × 4 MPPC arrays down to two surfaces. The sub-surface laser engraving technique was used to fabricate 3D grids into a monolithic crystal block. The 3D flood histograms were obtained by the Anger-type calculation. Two figures of merit, peak-to-valley ratios and distance-to-width ratios, were used to evaluate crystal identification performance. Clear separation was obtained even in the 2-surface configuration for the 3 mm X'tal cube, and the average peak-to-valley ratios and the distance-to-width ratios were 6.7 and 2.6, respectively. Meanwhile, in the 2 mm X'tal cube, the 6-surface configuration could separate all crystals and even the 2-surface case could also, but the flood histograms were relatively shrunk in the 2-surface case, especially on planes parallel to the sensitive surfaces. However, the minimum peak-to-valley ratio did not fall below 3.9. We concluded that reducing the numbers of MPPC readout surfaces was feasible for both the 3 mm and the 2 mm X'tal cubes.

  15. Spinning New Tales from Traditional Texts: Donna Jo Napoli and the Rewriting of Fairy Tale.

    ERIC Educational Resources Information Center

    Crew, Hilary S.

    2002-01-01

    Demonstrates how Donna Jo Napoli changes generic conventions and reworks discursive formations in order to retell tradition tales. Discusses the narrative strategies she uses in telling her stories, her representation of male and female characters in regard to gender and gendered relationships, and the way she renegotiates ideologies and value…

  16. A Tale of Four Electrons

    ERIC Educational Resources Information Center

    Burgmayer, Paul

    2011-01-01

    "A Tale of Four Electrons" is a creative writing assignment used with 10th-grade Honors Chemistry students. The project helps students consolidate their learning about bonding--an important unifying theme in chemistry--and answers questions such as (1) How are ionic, metallic, and covalent bonds related? (2) How do variations in electron…

  17. The Therapeutic Use of Fairy Tales with Adults in Group Therapy

    ERIC Educational Resources Information Center

    Brown, Nina W.

    2007-01-01

    Fairy tales are not just for children. They can hold important messages for people of all ages, as well as for those with special needs. For example, people who present for therapy reporting such issues as fear of abandonment, sibling rivalry, self-esteem, and lack of meaning in life, among others, can benefit from using fairy tales as a…

  18. Number Crunching: A Sheep's Tale

    ERIC Educational Resources Information Center

    Sam, Chris Lam

    2005-01-01

    In this article, the author talks about an allegorical tale which he has written as a message for teachers of mathematics. The story is about Gordon, who led a flock of small sheep. Gordon was a mathematics genius; however, his flock criticized his teaching of numbers and his boring lectures. His furry-god-farmer advised him to share his…

  19. [A tale of two encounters].

    PubMed

    Chanel, Marie-Paule

    The moving testimony of a patient shows the impact which a successful encounter can have. Beyond the positive clinical consequences, her rediscovered motivation and pleasure are the essential drivers which have guided her along the pathway of reconstruction. A tale of two encounters which have marked her life course. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. The Crystal Structure of TAL Effector PthXo1 Bound to Its DNA Target

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

    Mak, Amanda Nga-Sze; Bradley, Philip; Cernadas, Raul A.

    2012-02-10

    DNA recognition by TAL effectors is mediated by tandem repeats, each 33 to 35 residues in length, that specify nucleotides via unique repeat-variable diresidues (RVDs). The crystal structure of PthXo1 bound to its DNA target was determined by high-throughput computational structure prediction and validated by heavy-atom derivatization. Each repeat forms a left-handed, two-helix bundle that presents an RVD-containing loop to the DNA. The repeats self-associate to form a right-handed superhelix wrapped around the DNA major groove. The first RVD residue forms a stabilizing contact with the protein backbone, while the second makes a base-specific contact to the DNA sense strand.more » Two degenerate amino-terminal repeats also interact with the DNA. Containing several RVDs and noncanonical associations, the structure illustrates the basis of TAL effector-DNA recognition.« less

  1. Intrinsic spatial resolution evaluation of the X'tal cube PET detector based on a 3D crystal block segmented by laser processing.

    PubMed

    Yoshida, Eiji; Tashima, Hideaki; Inadama, Naoko; Nishikido, Fumihiko; Moriya, Takahiro; Omura, Tomohide; Watanabe, Mitsuo; Murayama, Hideo; Yamaya, Taiga

    2013-01-01

    The X'tal cube is a depth-of-interaction (DOI)-PET detector which is aimed at obtaining isotropic resolution by effective readout of scintillation photons from the six sides of a crystal block. The X'tal cube is composed of the 3D crystal block with isotropic resolution and arrays of multi-pixel photon counters (MPPCs). In this study, to fabricate the 3D crystal block efficiently and precisely, we applied a sub-surface laser engraving (SSLE) technique to a monolithic crystal block instead of gluing segmented small crystals. The SSLE technique provided micro-crack walls which carve a groove into a monolithic scintillator block. Using the fabricated X'tal cube, we evaluated its intrinsic spatial resolution to show a proof of concept of isotropic resolution. The 3D grids of 2 mm pitch were fabricated into an 18 × 18 × 18 mm(3) monolithic lutetium yttrium orthosilicate (LYSO) crystal by the SSLE technique. 4 × 4 MPPCs were optically coupled to each surface of the crystal block. The X'tal cube was uniformly irradiated by (22)Na gamma rays, and all of the 3D grids on the 3D position histogram were separated clearly by an Anger-type calculation from the 96-channel MPPC signals. Response functions of the X'tal cube were measured by scanning with a (22)Na point source. The gamma-ray beam with a 1.0 mm slit was scanned in 0.25 mm steps by positioning of the X'tal cube at vertical and 45° incident angles. The average FWHM resolution at both incident angles was 2.1 mm. Therefore, we confirmed the isotropic spatial resolution performance of the X'tal cube.

  2. Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors.

    PubMed

    Perdigão, Pedro; Gaj, Thomas; Santa-Marta, Mariana; Barbas, Carlos F; Goncalves, Joao

    2016-01-01

    The presence of replication-competent HIV-1 -which resides mainly in resting CD4+ T cells--is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE) proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection.

  3. Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors

    PubMed Central

    Perdigão, Pedro; Gaj, Thomas; Santa-Marta, Mariana; Goncalves, Joao

    2016-01-01

    The presence of replication-competent HIV-1 –which resides mainly in resting CD4+ T cells–is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE) proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection. PMID:26933881

  4. Forever Acting Alone: The Absence of Female Collaboration in "Grimms' Fairy Tales."

    ERIC Educational Resources Information Center

    Mendelson, Michael

    1997-01-01

    Explores the roles allocated to women in the famous collection. States that, although collaboration figures prominently in many of the more than 200 tales, the benefits of collective action are not extended to women. Examines the differences between male and female collaboration in the tales. Contemplates the implications of these differences for…

  5. To Be Specific or Not: The Critical Relationship Between Hox And TALE Proteins.

    PubMed

    Merabet, Samir; Mann, Richard S

    2016-06-01

    Hox proteins are key regulatory transcription factors that act in different tissues of the embryo to provide specific spatial and temporal coordinates to each cell. These patterning functions often depend on the presence of the TALE-homeodomain class cofactors, which form cooperative DNA-binding complexes with all Hox proteins. How this family of cofactors contributes to the highly diverse and specific functions of Hox proteins in vivo remains an important unsolved question. We review here the most recent advances in understanding the molecular mechanisms underlying Hox-TALE function. In particular, we discuss the role of DNA shape, DNA-binding affinity, and protein-protein interaction flexibility in dictating Hox-TALE specificity. We propose several models to explain how these mechanisms are integrated with each other in the context of the many distinct functions that Hox and TALE factors carry out in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes

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

    Li, T; Huang, S; Zhao, XF

    Recent studies indicate that the DNA recognition domain of transcription activator-like (TAL) effectors can be combined with the nuclease domain of FokI restriction enzyme to produce TAL effector nucleases (TALENs) that, in pairs, bind adjacent DNA target sites and produce double-strand breaks between the target sequences, stimulating non-homologous end-joining and homologous recombination. Here, we exploit the four prevalent TAL repeats and their DNA recognition cipher to develop a 'modular assembly' method for rapid production of designer TALENs (dTALENs) that recognize unique DNA sequence up to 23 bases in any gene. We have used this approach to engineer 10 dTALENs tomore » target specific loci in native yeast chromosomal genes. All dTALENs produced high rates of site-specific gene disruptions and created strains with expected mutant phenotypes. Moreover, dTALENs stimulated high rates (up to 34%) of gene replacement by homologous recombination. Finally, dTALENs caused no detectable cytotoxicity and minimal levels of undesired genetic mutations in the treated yeast strains. These studies expand the realm of verified TALEN activity from cultured human cells to an intact eukaryotic organism and suggest that low-cost, highly dependable dTALENs can assume a significant role for gene modifications of value in human and animal health, agriculture and industry.« less

  7. The Fantastic Tale for Children: A Genre Study from the Viewpoints of Literary and Educational Research.

    ERIC Educational Resources Information Center

    Klingberg, Gote

    The literary genre explored in this study is The Fantastic Tale for Children, which combines magic and reality. Two examples of the "pure" fantastic tale are "The Return of the Twelves" by Pauline Clarke and "Tom's Midnight Garden" by Philippa Pearce. The motifs of the fantastic tale are methods which connect the world of the principal characters…

  8. The Research Team Approach to Learning (ReTAL): A Structure for Open-Endedness.

    ERIC Educational Resources Information Center

    Del Giorno, Bette J.

    The ReTAL technique is described by using role sheets for the teacher and the student members of the research team; the "Researcher" defines the problem and searches the literature, the "Technician" plans and executes the experiment, and the "Recorder-Discussion Leader" coordinates records, interprets, evaluates, and reports the study. Each team…

  9. TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts.

    PubMed

    Bernstein, Diana L; Le Lay, John E; Ruano, Elena G; Kaestner, Klaus H

    2015-05-01

    Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator-like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. Together, our results demonstrate that TALE-DNMTs can selectively target specific genes and suggest that this strategy has potential application for the development of locus-specific epigenetic therapeutics.

  10. TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts

    PubMed Central

    Bernstein, Diana L.; Le Lay, John E.; Ruano, Elena G.; Kaestner, Klaus H.

    2015-01-01

    Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator–like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. Together, our results demonstrate that TALE-DNMTs can selectively target specific genes and suggest that this strategy has potential application for the development of locus-specific epigenetic therapeutics. PMID:25866970

  11. Nyberg with OGS R&R

    NASA Image and Video Library

    2013-07-19

    ISS036-E-021797 (18 July 2013) --- NASA astronaut Karen Nyberg, Expedition 36 flight engineer, performs a remove and replace of the Oxygen Generation System (OGS) Hydrogen (H2) Sensor in the Tranquility node of the International Space Station.

  12. "Clockwork": Philip Pullman's Posthuman Fairy Tale

    ERIC Educational Resources Information Center

    Gooding, Richard

    2011-01-01

    This article examines the connections between posthumanism and narrative form in Philip Pullman's "Clockwork." Beginning with an account of Pullman's materialism, it argues that the novel represents consciousness and agency as emergent properties of matter, a position that manifests itself first in the tale's figurative language and later in the…

  13. Expansion of TALE homeobox genes and the evolution of spiralian development.

    PubMed

    Morino, Yoshiaki; Hashimoto, Naoki; Wada, Hiroshi

    2017-12-01

    Spiralians, including molluscs, annelids and platyhelminths, share a unique development process that includes the typical geometry of early cleavage and early segregation of cell fate in blastomeres along the animal-vegetal axis. However, the molecular mechanisms underlying this early cell fate segregation are largely unknown. Here, we report spiralian-specific expansion of the three-amino-acid loop extension (TALE) class of homeobox genes. During early development, some of these TALE genes are expressed in staggered domains along the animal-vegetal axis in the limpet Nipponacmea fuscoviridis and the polychaete Spirobranchus kraussii. Inhibition or overexpression of these genes alters the developmental fate of blastomeres, as predicted by the gene expression patterns. These results suggest that the expansion of novel TALE genes plays a critical role in the establishment of a novel cell fate segregation mechanism in spiralians.

  14. Glimpse into Hox and tale regulation of cell differentiation and reprogramming.

    PubMed

    Cerdá-Esteban, Nuria; Spagnoli, Francesca M

    2014-01-01

    During embryonic development, cells become gradually restricted in their developmental potential and start elaborating lineage-specific transcriptional networks to ultimately acquire a unique differentiated state. Hox genes play a central role in specifying regional identities, thereby providing the cell with critical information on positional value along its differentiation path. The exquisite DNA-binding specificity of the Hox proteins is frequently dependent upon their interaction with members of the TALE family of homeodomain proteins. In addition to their function as Hox-cofactors, TALE homeoproteins control multiple crucial developmental processes through Hox-independent mechanisms. Here, we will review recent findings on the function of both Hox and TALE proteins in cell differentiation, referring mostly to vertebrate species. In addition, we will discuss the direct implications of this knowledge on cell plasticity and cell reprogramming. Copyright © 2013 Wiley Periodicals, Inc.

  15. ogs6 - a new concept for porous-fractured media simulations

    NASA Astrophysics Data System (ADS)

    Naumov, Dmitri; Bilke, Lars; Fischer, Thomas; Rink, Karsten; Wang, Wenqing; Watanabe, Norihiro; Kolditz, Olaf

    2015-04-01

    OpenGeoSys (OGS) is a scientific open-source initiative for numerical simulation of thermo-hydro-mechanical/chemical (THMC) processes in porous and fractured media, continuously developed since the mid-eighties. The basic concept is to provide a flexible numerical framework for solving coupled multi-field problems. OGS is targeting mainly on applications in environmental geoscience, e.g. in the fields of contaminant hydrology, water resources management, waste deposits, or geothermal energy systems, but it has also been successfully applied to new topics in energy storage recently. OGS is actively participating several international benchmarking initiatives, e.g. DECOVALEX (waste management), CO2BENCH (CO2 storage and sequestration), SeSBENCH (reactive transport processes) and HM-Intercomp (coupled hydrosystems). Despite the broad applicability of OGS in geo-, hydro- and energy-sciences, several shortcomings became obvious concerning the computational efficiency as well as the code structure became too sophisticated for further efficient development. OGS-5 was designed for object-oriented FEM applications. However, in many multi-field problems a certain flexibility of tailored numerical schemes is essential. Therefore, a new concept was designed to overcome existing bottlenecks. The paradigms for ogs6 are: - Flexibility of numerical schemes (FEM#FVM#FDM), - Computational efficiency (PetaScale ready), - Developer- and user-friendly. ogs6 has a module-oriented architecture based on thematic libraries (e.g. MeshLib, NumLib) on the large scale and uses object-oriented approach for the small scale interfaces. Usage of a linear algebra library (Eigen3) for the mathematical operations together with the ISO C++11 standard increases the expressiveness of the code and makes it more developer-friendly. The new C++ standard also makes the template meta-programming technique code used for compile-time optimizations more compact. We have transitioned the main code development to

  16. Co-expression of TAL1 and ADH1 in recombinant xylose-fermenting Saccharomyces cerevisiae improves ethanol production from lignocellulosic hydrolysates in the presence of furfural.

    PubMed

    Hasunuma, Tomohisa; Ismail, Ku Syahidah Ku; Nambu, Yumiko; Kondo, Akihiko

    2014-02-01

    Lignocellulosic biomass dedicated to bioethanol production usually contains pentoses and inhibitory compounds such as furfural that are not well tolerated by Saccharomyces cerevisiae. Thus, S. cerevisiae strains with the capability of utilizing both glucose and xylose in the presence of inhibitors such as furfural are very important in industrial ethanol production. Under the synergistic conditions of transaldolase (TAL) and alcohol dehydrogenase (ADH) overexpression, S. cerevisiae MT8-1X/TAL-ADH was able to produce 1.3-fold and 2.3-fold more ethanol in the presence of 70 mM furfural than a TAL-expressing strain and a control strain, respectively. We also tested the strains' ability by mimicking industrial ethanol production from hemicellulosic hydrolysate containing fermentation inhibitors, and ethanol production was further improved by 16% when using MT8-1X/TAL-ADH compared to the control strain. Transcript analysis further revealed that besides the pentose phosphate pathway genes TKL1 and TAL1, ADH7 was also upregulated in response to furfural stress, which resulted in higher ethanol production compared to the TAL-expressing strain. The improved capability of our modified strain was based on its capacity to more quickly reduce furfural in situ resulting in higher ethanol production. The co-expression of TAL/ADH genes is one crucial strategy to fully utilize undetoxified lignocellulosic hydrolysate, leading to cost-competitive ethanol production. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  17. Oral Interpretation of C.S. Lewis'"Narnia Tales": A Refracting of "Pictures."

    ERIC Educational Resources Information Center

    Keefe, Carolyn

    "The Chronicles of Narnia" are a series of seven fairy tales written by C.S. Lewis that have become popular with both children and adults. Lewis points to five aspects of the fairy tale form that made the form suitable for expressing the images he saw. The aspects are: (1) no love interest; (2) no close psychology; (3) severe restraints…

  18. Regulation of endogenous human gene expression by ligand-inducible TALE transcription factors.

    PubMed

    Mercer, Andrew C; Gaj, Thomas; Sirk, Shannon J; Lamb, Brian M; Barbas, Carlos F

    2014-10-17

    The construction of increasingly sophisticated synthetic biological circuits is dependent on the development of extensible tools capable of providing specific control of gene expression in eukaryotic cells. Here, we describe a new class of synthetic transcription factors that activate gene expression in response to extracellular chemical stimuli. These inducible activators consist of customizable transcription activator-like effector (TALE) proteins combined with steroid hormone receptor ligand-binding domains. We demonstrate that these ligand-responsive TALE transcription factors allow for tunable and conditional control of gene activation and can be used to regulate the expression of endogenous genes in human cells. Since TALEs can be designed to recognize any contiguous DNA sequence, the conditional gene regulatory system described herein will enable the design of advanced synthetic gene networks.

  19. "Thou" and "Ye" in Chaucer's "Clerk's Tale."

    ERIC Educational Resources Information Center

    Wilcockson, Colin

    1980-01-01

    Examines the use of the second person pronoun in Chaucer's "Clerk's Tale" to demonstrate that students of medieval texts may well miss important areas of meaning if they fail to give adequate attention to the historical study of language. (GT)

  20. A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria.

    PubMed

    Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2016-07-29

    Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens.

  1. A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria

    PubMed Central

    Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2016-01-01

    Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens. DOI: http://dx.doi.org/10.7554/eLife.19605.001 PMID:27472897

  2. Tales from the Twitterverse

    NASA Astrophysics Data System (ADS)

    deGrasse Tyson, N.

    2012-08-01

    "Tales from the Twitterverse" describes Dr. Tyson's running experience communicating science via the medium of Twitter. He now has about 130,000 followers on his twitter handle @neiltyson and was recently selected for Time Magazine's list of the best 140 Twitter feeds. It is perhaps fair to say that, so far, social media and science EPO have not yet been fully introduced to one another. So this plenary talk will be a kind of overview of his successes and failures in the medium, as a way to jumpstart people's interest in what is possible.

  3. Fairy Tales and Fantasy: Bridges to Literature--Using Fairy Tales and Fantasy to Motivate the Reluctant Reader.

    ERIC Educational Resources Information Center

    Dungey, Joan M.

    Designed to give children a sense of the cultural heritage that fairy tales represent, this instructional unit was originally developed to motivate eighth-grade low-level readers and was later adapted for English as a second language classes and for a variety of elementary and secondary school learning levels. Objectives of the unit are to help…

  4. Using Jack Tales in a Second Grade Class.

    ERIC Educational Resources Information Center

    Brown, Doris

    1987-01-01

    Describes a project in which Kentucky second grades developed puppet shows and photography activities based on traditional Appalachian oral tales. Discusses student progress in language arts skills, creativity, use of audiovisual equipment, and group cooperation. (SV)

  5. TAL effector driven induction of a SWEET gene confers susceptibility to bacterial blight of cotton

    USDA-ARS?s Scientific Manuscript database

    Bacterial blight of cotton (BBC), caused by Xanthomonas citri subsp. malvacearum (Xcm), is among the most destructive diseases in cotton (Gossypium spp.). Transcription activator-like (TAL) effectors from Xcm are essential for BBC disease progression. Here, we carried out whole-genome PacBio-seque...

  6. Tales of Wisdom in Folly. A Course in Controlled Composition. Program and Training Journal Reprint Series, No. 13.

    ERIC Educational Resources Information Center

    Kayeum, Joan

    This booklet is a collection of Mullah Nasruddin tales that are commonly enjoyed in Afghanistan. These tales have been adapted to form a course in controlled composition for students studying English as a foreign language. After reading each tale the student is asked to carry out certain tasks. In addition to the simplest task, copying the passage…

  7. Application of TALE-Based Approach for Dissecting Functional MicroRNA-302/367 in Cellular Reprogramming.

    PubMed

    Zhang, Zhonghui; Wu, Wen-Shu

    2018-01-01

    MicroRNAs are small 18-24 nt single-stranded noncoding RNA molecules involved in many biological processes, including stemness maintenance and cellular reprogramming. Current methods used in loss-of-function studies of microRNAs have several limitations. Here, we describe a new approach for dissecting miR-302/367 functions by transcription activator-like effectors (TALEs), which are natural effector proteins secreted by Xanthomonas and Ralstonia bacteria. Knockdown of the miR-302/367 cluster uses the Kruppel-associated box repressor domain fused with specific TALEs designed to bind the miR-302/367 cluster promoter. Knockout of the miR-302/367 cluster uses two pairs of TALE nucleases (TALENs) to delete the miR-302/367 cluster in human primary cells. Together, both TALE-based transcriptional repressor and TALENs are two promising approaches for loss-of-function studies of microRNA cluster in human primary cells.

  8. Characterization of TALE genes expression during the first lineage segregation in mammalian embryos.

    PubMed

    Sonnet, Wendy; Rezsöhazy, Rene; Donnay, Isabelle

    2012-11-01

    Three amino acid loop extension (TALE) homeodomain-containing transcription factors are generally recognized for their role in organogenesis and differentiation during embryogenesis. However, very little is known about the expression and function of Meis, Pbx, and Prep genes during early development. In order to determine whether TALE proteins could contribute to the early cell fate decisions in mammalian development, this study aimed to characterize in a systematic manner the pattern of expression of all Meis, Pbx, and Prep genes from the precompaction to blastocyst stage corresponding to the first step of cell differentiation in mammals. To reveal to what extent TALE genes expression at these early stages is a conserved feature among mammals, this study was performed in parallel in the bovine and mouse models. We demonstrated the transcription and translation of TALE genes, before gastrulation in the two species. At least one member of Meis, Pbx, and Prep subfamilies was found expressed at the RNA and protein levels but different patterns of expression were observed between genes and between species, suggesting specific gene regulations. Taken together, these results suggest a previously unexpected involvement of these factors during the early development in mammals. Copyright © 2012 Wiley Periodicals, Inc.

  9. A Study on Choosing Tales for Utilising as Teaching Materials in Turkish Language Education

    ERIC Educational Resources Information Center

    Ayranci, Bilge Bagci

    2017-01-01

    Fairy tales are used intensively by Turkish teachers in Turkish lessons. Elements in tales need to be examined in many respects such as their suitability for cultural transmission, psychological benefits, and harms, correct and effective use of language and so on. The opinions of the Turkish teachers in the field are very important for this…

  10. Interrogating Key Positions of Size-Reduced TALE Repeats Reveals a Programmable Sensor of 5-Carboxylcytosine.

    PubMed

    Maurer, Sara; Giess, Mario; Koch, Oliver; Summerer, Daniel

    2016-12-16

    Transcription-activator-like effector (TALE) proteins consist of concatenated repeats that recognize consecutive canonical nucleobases of DNA via the major groove in a programmable fashion. Since this groove displays unique chemical information for the four human epigenetic cytosine nucleobases, TALE repeats with epigenetic selectivity can be engineered, with potential to establish receptors for the programmable decoding of all human nucleobases. TALE repeats recognize nucleobases via key amino acids in a structurally conserved loop whose backbone is positioned very close to the cytosine 5-carbon. This complicates the engineering of selectivities for large 5-substituents. To interrogate a more promising structural space, we engineered size-reduced repeat loops, performed saturation mutagenesis of key positions, and screened a total of 200 repeat-nucleobase interactions for new selectivities. This provided insight into the structural requirements of TALE repeats for affinity and selectivity, revealed repeats with improved or relaxed selectivity, and resulted in the first selective sensor of 5-carboxylcytosine.

  11. HOXA1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on HOXA1 targets

    PubMed Central

    De Kumar, Bony; Parker, Hugo J.; Paulson, Ariel; Parrish, Mark E.; Pushel, Irina; Singh, Narendra Pratap; Zhang, Ying; Slaughter, Brian D.; Unruh, Jay R.; Florens, Laurence; Zeitlinger, Julia; Krumlauf, Robb

    2017-01-01

    Hoxa1 has diverse functional roles in differentiation and development. We identify and characterize properties of regions bound by HOXA1 on a genome-wide basis in differentiating mouse ES cells. HOXA1-bound regions are enriched for clusters of consensus binding motifs for HOX, PBX, and MEIS, and many display co-occupancy of PBX and MEIS. PBX and MEIS are members of the TALE family and genome-wide analysis of multiple TALE members (PBX, MEIS, TGIF, PREP1, and PREP2) shows that nearly all HOXA1 targets display occupancy of one or more TALE members. The combinatorial binding patterns of TALE proteins define distinct classes of HOXA1 targets, which may create functional diversity. Transgenic reporter assays in zebrafish confirm enhancer activities for many HOXA1-bound regions and the importance of HOX-PBX and TGIF motifs for their regulation. Proteomic analyses show that HOXA1 physically interacts on chromatin with PBX, MEIS, and PREP family members, but not with TGIF, suggesting that TGIF may have an independent input into HOXA1-bound regions. Therefore, TALE proteins appear to represent a wide repertoire of HOX cofactors, which may coregulate enhancers through distinct mechanisms. We also discover extensive auto- and cross-regulatory interactions among the Hoxa1 and TALE genes, indicating that the specificity of HOXA1 during development may be regulated though a complex cross-regulatory network of HOXA1 and TALE proteins. This study provides new insight into a regulatory network involving combinatorial interactions between HOXA1 and TALE proteins. PMID:28784834

  12. The Monets, Van Goghs, and Renoirs of Science Education: Writing Impressionist Tales as a Strategy for Facilitating Prospective Teachers' Reflections on Science Experiences

    NASA Astrophysics Data System (ADS)

    Bryan, Lynn A.; Tippins, Deborah J.

    2005-08-01

    A particularly useful pedagogical strategy for beginning a dialogue with prospective teachers about the ways in which their experiences and beliefs shape their development of professional knowledge is writing impressionist tales. Impressionist tales are a form of autobiography that portrays one highly personal perspective on a significant moment in time. In this pedagogical practice article, we describe our use of impressionist tales, summarize the assumptions underpinning our use of impressionist tales in science methods courses, provide several examples of our students’ tales, and discuss the pedagogical advantages and the teacher educator’s role in using impressionist tales to promote reflective thinking among prospective elementary science teachers.

  13. Understanding "A Tale of Two Cities": A Student Casebook to Issues, Sources, and Historical Documents.

    ERIC Educational Resources Information Center

    Newlin, George

    Charles Dickens' novel, "A Tale of Two Cities," does not waste a word in telling a touching, suspenseful tale set against the background of one of the bloodiest events in history, the French Revolution. This casebook's collection of historical documents, collateral readings, and commentary will promote interdisciplinary study of the…

  14. Context influences on TALE–DNA binding revealed by quantitative profiling

    PubMed Central

    Rogers, Julia M.; Barrera, Luis A.; Reyon, Deepak; Sander, Jeffry D.; Kellis, Manolis; Joung, J Keith; Bulyk, Martha L.

    2015-01-01

    Transcription activator-like effector (TALE) proteins recognize DNA using a seemingly simple DNA-binding code, which makes them attractive for use in genome engineering technologies that require precise targeting. Although this code is used successfully to design TALEs to target specific sequences, off-target binding has been observed and is difficult to predict. Here we explore TALE–DNA interactions comprehensively by quantitatively assaying the DNA-binding specificities of 21 representative TALEs to ∼5,000–20,000 unique DNA sequences per protein using custom-designed protein-binding microarrays (PBMs). We find that protein context features exert significant influences on binding. Thus, the canonical recognition code does not fully capture the complexity of TALE–DNA binding. We used the PBM data to develop a computational model, Specificity Inference For TAL-Effector Design (SIFTED), to predict the DNA-binding specificity of any TALE. We provide SIFTED as a publicly available web tool that predicts potential genomic off-target sites for improved TALE design. PMID:26067805

  15. Development of a DOI PET Detector Having the Structure of the X'tal Cube Extended in One Direction

    NASA Astrophysics Data System (ADS)

    Inadama, Naoko; Hirano, Yoshiyuki; Nishikido, Fumihiko; Murayama, Hideo; Yamaya, Taiga

    2016-10-01

    X'tal cube is the cubic depth of interaction (DOI) PET detector which our research group developed. In this work, aiming to get higher sensitivity, we developed the long rectangular shape X'tal cube (long-XC) by extending the cubic X'tal cube structure in one direction. We verified performance of this long-XC and also studied detector parameters for optimization. The same as the X'tal cube, the crystal block of the long-XC is composed of a 3D array of cubic scintillation crystal elements. Reflectors are not inserted between these crystal elements. The scintillation light then spreads without being obstructed by reflectors and is detected by multiple numbers of the multi-pixel photon counters (MPPCs) coupled on all six sides of the crystal block. For crystal element identification, a simple Anger-type calculation is used. In this study, we arranged 3.0 mm×3.0 mm×3.0 mm LGSO crystal elements in a 6 × 6 × 14 array for the long-XC. In a previous study, we had already confirmed that for the X'tal cube consisting of a 6 × 6 × 6 array of the same crystal elements and 54 MPPCs, identification of all 216 crystal elements was possible and the average energy resolution for all the elements was about 11 %. The long-XC contains more than twice the number of the crystal elements but less than twice the number of the MPPCs compared to the previous X'tal cube. The detector parameters investigated with the long-XC were: the number of MPPCs on both sides in the extended direction (edge MPPCs); the MPPC type, the MPPCs of 25 μm × 25 μm or 50 μm × 50 μm pixel sizes; the material between the crystal elements, an air gap or an optical glue having a closer refractive index to that of LGSO than air has; and the MPPC signals used in the Anger-type calculation. Results of the crystal element identification performance showed that reducing the number of the edge MPPCs caused performance degradation only at the part near the edge. For the MPPC type, the 50 μm type was better than

  16. Locked and proteolysis-based transcription activator-like effector (TALE) regulation.

    PubMed

    Lonzarić, Jan; Lebar, Tina; Majerle, Andreja; Manček-Keber, Mateja; Jerala, Roman

    2016-02-18

    Development of orthogonal, designable and adjustable transcriptional regulators is an important goal of synthetic biology. Their activity has been typically modulated through stimulus-induced oligomerization or interaction between the DNA-binding and activation/repression domain. We exploited a feature of the designable Transcription activator-like effector (TALE) DNA-binding domain that it winds around the DNA which allows to topologically prevent it from binding by intramolecular cyclization. This new approach was investigated through noncovalent ligand-induced cyclization or through a covalent split intein cyclization strategy, where the topological inhibition of DNA binding by cyclization and its restoration by a proteolytic release of the topologic constraint was expected. We show that locked TALEs indeed have diminished DNA binding and regain full transcriptional activity by stimulation with the rapamycin ligand or site-specific proteolysis of the peptide linker, with much higher level of activation than rapamycin-induced heterodimerization. Additionally, we demonstrated reversibility, activation of genomic targets and implemented logic gates based on combinations of protein cyclization, proteolytic cleavage and ligand-induced dimerization, where the strongest fold induction was achieved by the proteolytic cleavage of a repression domain from a linear TALE. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. HOXA1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on HOXA1 targets.

    PubMed

    De Kumar, Bony; Parker, Hugo J; Paulson, Ariel; Parrish, Mark E; Pushel, Irina; Singh, Narendra Pratap; Zhang, Ying; Slaughter, Brian D; Unruh, Jay R; Florens, Laurence; Zeitlinger, Julia; Krumlauf, Robb

    2017-09-01

    Hoxa1 has diverse functional roles in differentiation and development. We identify and characterize properties of regions bound by HOXA1 on a genome-wide basis in differentiating mouse ES cells. HOXA1-bound regions are enriched for clusters of consensus binding motifs for HOX, PBX, and MEIS, and many display co-occupancy of PBX and MEIS. PBX and MEIS are members of the TALE family and genome-wide analysis of multiple TALE members (PBX, MEIS, TGIF, PREP1, and PREP2) shows that nearly all HOXA1 targets display occupancy of one or more TALE members. The combinatorial binding patterns of TALE proteins define distinct classes of HOXA1 targets, which may create functional diversity. Transgenic reporter assays in zebrafish confirm enhancer activities for many HOXA1-bound regions and the importance of HOX-PBX and TGIF motifs for their regulation. Proteomic analyses show that HOXA1 physically interacts on chromatin with PBX, MEIS, and PREP family members, but not with TGIF, suggesting that TGIF may have an independent input into HOXA1-bound regions. Therefore, TALE proteins appear to represent a wide repertoire of HOX cofactors, which may coregulate enhancers through distinct mechanisms. We also discover extensive auto- and cross-regulatory interactions among the Hoxa1 and TALE genes, indicating that the specificity of HOXA1 during development may be regulated though a complex cross-regulatory network of HOXA1 and TALE proteins. This study provides new insight into a regulatory network involving combinatorial interactions between HOXA1 and TALE proteins. © 2017 De Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Physical characteristics of Comet Nucleus C/2001 OG 108 (LONEOS)

    NASA Astrophysics Data System (ADS)

    Abell, Paul A.; Fernández, Yanga R.; Pravec, Petr; French, Linda M.; Farnham, Tony L.; Gaffey, Michael J.; Hardersen, Paul S.; Kušnirák, Peter; Šarounová, Lenka; Sheppard, Scott S.; Narayan, Gautham

    2005-12-01

    A detailed description of the Halley-type Comet C/2001 OG 108 (LONEOS) has been derived from visible, near-infrared, and mid-infrared observations obtained in October and November 2001. These data represent the first high-quality ground-based observations of a bare Halley-type comet nucleus and provide the best characterization of a Halley-type comet other than 1P/Halley itself. Analysis of time series photometry suggests that the nucleus has a rotation period of 57.2±0.5 h with a minimum nuclear axial ratio of 1.3, a phase-darkening slope parameter G of -0.01±0.10, and an estimated H=13.05±0.10. The rotation period of C/2001 OG 108 is one of the longest observed among comet nuclei. The V- R color index for this object is measured to be 0.46±0.02, which is virtually identical to that of other cometary nuclei and other possible extinct comet candidates. Measurements of the comet's thermal emission constrain the projected elliptical nuclear radii to be 9.6±1.0 km and 7.4±1.0 km, which makes C/2001 OG 108 one of the larger cometary nuclei known. The derived geometric albedo in V-band of 0.040±0.010 is typical for comet nuclei. Visible-wavelength spectrophotometry and near-infrared spectroscopy were combined to derive the nucleus's reflectance spectrum over a 0.4 to 2.5 μm wavelength range. These measurements represent one of the few nuclear spectra ever observed and the only known spectrum of a Halley-type comet. The spectrum of this comet nucleus is very nearly linear and shows no discernable absorption features at a 5% detection limit. The lack of any features, especially in the 0.8 to 1.0 μm range such as are seen in the spectra of carbonaceous chondrite meteorites and many low-albedo asteroids, is consistent with the presence of anhydrous rather than hydrous silicates on the surface of this comet. None of the currently recognized meteorites in the terrestrial collections have reflectance spectra that match C/2001 OG 108. The near-infrared spectrum, the

  19. A Case Study of Editorial Filters in Folktales: A Discussion of the "Allerleirauh" Tales in Grimm.

    ERIC Educational Resources Information Center

    Dollerup, Cay; And Others

    1986-01-01

    This article discusses editorial "filters" in folktales, specifically the changes ("orientations") which editors deliberately impose on a tale because they want to reach a specific audience. A case in point is the tale called "Allerleirauh," in the Grimm collection, which not only is highly illustrative of editorial…

  20. Survey on Effects of Fairy Tales on Turkish Language Training from Secondary School Students' Perspective

    ERIC Educational Resources Information Center

    Kiliç, Yasin

    2015-01-01

    Fairy tale is one of the most important genres in literature which reflects childish sensitivity, feeds child's soul, enriches his/her imagination and prepares him/her for the future. Emerging as product of oral literature, fairy tales were used as an instrument of training in the past and they still have the same function today. Educators think…

  1. Psychoanalysis and detective fiction: a tale of Freud and criminal storytelling.

    PubMed

    Yang, Amy

    2010-01-01

    Much has been written about Freud's influence on popular culture. This article addresses the influence of literature on Freud's psychoanalytical theory, specifically the role that modern detective fiction played in shaping Freudian theory. Edgar Allan Poe gave Freud the literary precedent; Sir Arthur Conan Doyle's creation Sherlock Holmes gave him the analytical model. In turn, the world of crime story-telling embedded Freudian theories in subsequent forms, spinning the tales of crime into a journey into the human mind. As these tales were popularized on the silver screen in the early 20th century, psychoanalytical ideas moved from the lecture halls into the cultural mainstream.

  2. Engaging with Mathematics in the Kindergarten. Orchestrating a Fairy Tale through Questioning and Use of Tools

    ERIC Educational Resources Information Center

    Carlsen, Martin

    2013-01-01

    The aim of this study is to analyse how a kindergarten teacher orchestrated a mathematical activity involving a fairy tale. Taking a sociocultural perspective on learning and development, naturally occurring talk-in-interaction has been analysed in order to scrutinise the subtleties of the orchestration. The fairy tale "Goldilocks and the…

  3. A Salamander Tale: Effective Exhibits and Attitude Change

    ERIC Educational Resources Information Center

    Rollins, Jeffrey; Watson, Sunnie Lee

    2017-01-01

    Little information exists regarding intention behind the design and development of Extension outreach and educational exhibits. An evaluation of response to the exhibit "A Salamander Tale" indicates that the methods used to develop the exhibit resulted in an effective way to present information to an adult audience. Survey questions were…

  4. The Lobster Tale: An Exercise in Critical Thinking

    ERIC Educational Resources Information Center

    Stepanovich, Paul L.

    2009-01-01

    Professors in management and business are encouraged to incorporate critical thinking as an objective in their courses. "The Lobster Tale" provides an opportunity to engage students in various levels of critical thinking, ranging from a relatively superficial reading to an examination of the deeper, often hidden issues. Using the foundations of…

  5. Telling Different Tales: Possible Childhoods in Children's Literature

    ERIC Educational Resources Information Center

    Sreenivas, Deepa

    2011-01-01

    This article draws on the insights/questions that emerged while putting together a set of stories for children published in a series named "Different Tales." These stories, set in Dalit and other minority communities, problematize the normative grids through which we view "childhood" as they depict the complex ways in which…

  6. A multiplexable TALE-based binary expression system for in vivo cellular interaction studies.

    PubMed

    Toegel, Markus; Azzam, Ghows; Lee, Eunice Y; Knapp, David J H F; Tan, Ying; Fa, Ming; Fulga, Tudor A

    2017-11-21

    Binary expression systems have revolutionised genetic research by enabling delivery of loss-of-function and gain-of-function transgenes with precise spatial-temporal resolution in vivo. However, at present, each existing platform relies on a defined exogenous transcription activator capable of binding a unique recognition sequence. Consequently, none of these technologies alone can be used to simultaneously target different tissues or cell types in the same organism. Here, we report a modular system based on programmable transcription activator-like effector (TALE) proteins, which enables parallel expression of multiple transgenes in spatially distinct tissues in vivo. Using endogenous enhancers coupled to TALE drivers, we demonstrate multiplexed orthogonal activation of several transgenes carrying cognate variable activating sequences (VAS) in distinct neighbouring cell types of the Drosophila central nervous system. Since the number of combinatorial TALE-VAS pairs is virtually unlimited, this platform provides an experimental framework for highly complex genetic manipulation studies in vivo.

  7. Shrews, rats, and a polecat in "the pardoner’s tale": Chapter 3

    USGS Publications Warehouse

    Feinstein, Sandy; Woodman, Neal; Van Dyke, Carolynn

    2012-01-01

    While historically existing animals and literary animal characters inform allegorical and metaphorical characterization in The Canterbury Tales, figurative usage does not erase recognition of the material animal. "The Pardoner's Tale," for one, challenges the terms of conventional animal metaphors by refocusing attention on common animals as common animals and common human creatures as something worse than vermin. Most attention has been paid to the larger animals-goat, hare, and horse-that constitute the physical portrait of Chaucer's Pardoner in the "General Prologue" and in the prologue to his tale.! Like these animals, rats and a polecat, together with rhetorical shrews, appear in this tale as well as in other literature, including bestiaries and natural histories. Equally to the purpose, these animals could be physically observed as constituents of both urban and rural landscapes in fourteenth-century England.2 In the Middle Ages, animals were part of the environment as well as part of the culture: they lived inside as well as outside the city gates, priory walls, and even domestic spaces; a rat in the street or the garden might not be any less welcome or uncommon than encountering someone's horses and goats nibbling vegetation or blocking a passage. Not being out of the ordinary, though, such animals could (and can) be overlooked or dismissed as com­mon, too familiar to register. This chapter reveals why readers and listeners should pay close attention to the things they think they know and what they hear about what they think they know.

  8. Direct activation of human and mouse Oct4 genes using engineered TALE and Cas9 transcription factors

    PubMed Central

    Hu, Jiabiao; Lei, Yong; Wong, Wing-Ki; Liu, Senquan; Lee, Kai-Chuen; He, Xiangjun; You, Wenxing; Zhou, Rui; Guo, Jun-Tao; Chen, Xiongfong; Peng, Xianlu; Sun, Hao; Huang, He; Zhao, Hui; Feng, Bo

    2014-01-01

    The newly developed transcription activator-like effector protein (TALE) and clustered regularly interspaced short palindromic repeats/Cas9 transcription factors (TF) offered a powerful and precise approach for modulating gene expression. In this article, we systematically investigated the potential of these new tools in activating the stringently silenced pluripotency gene Oct4 (Pou5f1) in mouse and human somatic cells. First, with a number of TALEs and sgRNAs targeting various regions in the mouse and human Oct4 promoters, we found that the most efficient TALE-VP64s bound around −120 to −80 bp, while highly effective sgRNAs targeted from −147 to −89-bp upstream of the transcription start sites to induce high activity of luciferase reporters. In addition, we observed significant transcriptional synergy when multiple TFs were applied simultaneously. Although individual TFs exhibited marginal activity to up-regulate endogenous gene expression, optimized combinations of TALE-VP64s could enhance endogenous Oct4 transcription up to 30-fold in mouse NIH3T3 cells and 20-fold in human HEK293T cells. More importantly, the enhancement of OCT4 transcription ultimately generated OCT4 proteins. Furthermore, examination of different epigenetic modifiers showed that histone acetyltransferase p300 could enhance both TALE-VP64 and sgRNA/dCas9-VP64 induced transcription of endogenous OCT4. Taken together, our study suggested that engineered TALE-TF and dCas9-TF are useful tools for modulating gene expression in mammalian cells. PMID:24500196

  9. Direct activation of human and mouse Oct4 genes using engineered TALE and Cas9 transcription factors.

    PubMed

    Hu, Jiabiao; Lei, Yong; Wong, Wing-Ki; Liu, Senquan; Lee, Kai-Chuen; He, Xiangjun; You, Wenxing; Zhou, Rui; Guo, Jun-Tao; Chen, Xiongfong; Peng, Xianlu; Sun, Hao; Huang, He; Zhao, Hui; Feng, Bo

    2014-04-01

    The newly developed transcription activator-like effector protein (TALE) and clustered regularly interspaced short palindromic repeats/Cas9 transcription factors (TF) offered a powerful and precise approach for modulating gene expression. In this article, we systematically investigated the potential of these new tools in activating the stringently silenced pluripotency gene Oct4 (Pou5f1) in mouse and human somatic cells. First, with a number of TALEs and sgRNAs targeting various regions in the mouse and human Oct4 promoters, we found that the most efficient TALE-VP64s bound around -120 to -80 bp, while highly effective sgRNAs targeted from -147 to -89-bp upstream of the transcription start sites to induce high activity of luciferase reporters. In addition, we observed significant transcriptional synergy when multiple TFs were applied simultaneously. Although individual TFs exhibited marginal activity to up-regulate endogenous gene expression, optimized combinations of TALE-VP64s could enhance endogenous Oct4 transcription up to 30-fold in mouse NIH3T3 cells and 20-fold in human HEK293T cells. More importantly, the enhancement of OCT4 transcription ultimately generated OCT4 proteins. Furthermore, examination of different epigenetic modifiers showed that histone acetyltransferase p300 could enhance both TALE-VP64 and sgRNA/dCas9-VP64 induced transcription of endogenous OCT4. Taken together, our study suggested that engineered TALE-TF and dCas9-TF are useful tools for modulating gene expression in mammalian cells.

  10. Efficient Modification of the CCR5 Locus in Primary Human T Cells With megaTAL Nuclease Establishes HIV-1 Resistance

    PubMed Central

    Romano Ibarra, Guillermo S; Paul, Biswajit; Sather, Blythe D; Younan, Patrick M; Sommer, Karen; Kowalski, John P; Hale, Malika; Stoddard, Barry; Jarjour, Jordan; Astrakhan, Alexander; Kiem, Hans-Peter; Rawlings, David J

    2016-01-01

    A naturally occurring 32-base pair deletion of the HIV-1 co-receptor CCR5 has demonstrated protection against HIV infection of human CD4+ T cells. Recent genetic engineering approaches using engineered nucleases to disrupt the gene and mimic this mutation show promise for HIV therapy. We developed a megaTAL nuclease targeting the third extracellular loop of CCR5 that we delivered to primary human T cells by mRNA transfection. The CCR5 megaTAL nuclease established resistance to HIV in cell lines and disrupted the expression of CCR5 on primary human CD4+ T cells with a high efficiency, achieving up to 80% modification of the locus in primary cells as measured by molecular analysis. Gene-modified cells engrafted at levels equivalent to unmodified cells when transplanted into immunodeficient mice. Furthermore, genetically modified CD4+ cells were preferentially expanded during HIV-1 infection in vivo in an immunodeficient mouse model. Our results demonstrate the feasibility of targeting CCR5 in primary T cells using an engineered megaTAL nuclease, and the potential to use gene-modified cells to reconstitute a patient's immune system and provide protection from HIV infection. PMID:27741222

  11. Double Perspectives: Old Tales in Modern Novels.

    ERIC Educational Resources Information Center

    Perkins, Agnes

    There is a wealth of material in the oral tradition of fantasy which can be used in creating gripping fiction for young readers. One way of employing a tale from the oral tradition to produce a modern fantasy is to superimpose the old story on a new one in such a way that it is tightly interwoven in the action and meaning of the new story. This…

  12. The fairy tale as paradigm of the separation-individuation crisis: implications for treatment of the borderline adolescent.

    PubMed

    Brandt, L M

    1983-01-01

    This chapter is an attempt to offer a model for therapeutic work with borderline patients that is based on the structure and content of the fairy tale. It views the fairy tale as both descriptive in its echoing of developmental struggles of childhood and integrative in providing a model for resolution of these conflicts. Clare's use of the fairy tale offers confirmation of theoretical notions which place the etiology of borderline pathology in early developmental failures and a clue to the therapeutic work with borderline patients. While the childhood route of the fairy tale may no longer be available to most, its subtle mirroring of the separation-individuation crisis and gradual, growthful steps toward integration of both the external and the internal worlds offer an exquisite model for the work of psychotherapy. "Once a king in Narnia , always a king in Narnia . But don't go trying to use the same route twice. . ." (Lewis 1950, p. 186).

  13. Emily and Rebecca: A Tale of Two Teachers

    ERIC Educational Resources Information Center

    Brown, S.W.

    2005-01-01

    Using a qualitative study, two teachers, Emily and Rebecca, who started their teaching careers in their forties were interviewed and followed for 3 years to document their experiences in the teaching profession. The tale of these two teachers includes their joys, frustrations, and problems that surround their lives as middle school math teachers.…

  14. Shallow subsurface structures and geotechnical characteristics of Tal El-Amarna area, middle Egypt

    NASA Astrophysics Data System (ADS)

    Toni, Mostafa; Hosny, Ahmed; Attia, Mohsen M.; Hassoup, Awad; El-Sharkawy, Amr

    2013-12-01

    The shallow seismic refraction profiling was carried out at 18 sites in Tal El-Amarna, which is a flat area on the eastern bank of the Nile River, 50 km south of El Minia Governorate, middle Egypt. The collected data are used to estimate the P-wave velocity and to delineate the near-surface ground model beneath the study area. This study is supported by the National Research Institute of Astronomy and Geophysics due to the historical interest of the Tal El-Amarna area as a famous tourist place where there exist many Pharaoh temples and tombs. This area is low seismically active, but it is probably of high vulnerability due to the influence of the local geological conditions on earthquake ground motion, as well as the presence of poor constructions in the absence of various issues such as building designs, quality of building materials, etc. Another dataset at the study area is obtained by multi-channel passive source (microtremor) measurements, which have been recorded at four arrays. The frequency-wavenumber (f-k) method was used to derive the dispersion curves from the raw signals at each array. The resulted dispersion curves were inverted using the neighborhood algorithm to obtain the shear and P-wave velocity models. The concluded Vs and Vp values provide a preliminary estimation of the geotechnical parameters and site classification for the shallow soil as they are of great interest in civil engineering applications.

  15. Identification and Characterization of TALE Homeobox Genes in the Endangered Fern Vandenboschia speciosa

    PubMed Central

    Ruiz-Estévez, Mercedes; Martín-Blázquez, Rubén; Garrido-Ramos, Manuel A.

    2017-01-01

    We report and discuss the results of a quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of the expression patterns of seven three amino acid loop extension (TALE) homeobox genes (four KNOTTED-like homeobox (KNOX) and three BEL1-like homeobox (BELL) genes) identified after next generation sequencing (NGS) and assembly of the sporophyte and gametophyte transcriptomes of the endangered fern species Vandenboschia speciosa. Among the four KNOX genes, two belonged to the KNOX1 class and the other two belonged to the KNOX2 class. Analysis of the deduced amino acid sequences supported the typical domain structure of both types of TALE proteins, and the homology to TALE proteins of mosses, lycophytes, and seed plant species. The expression analyses demonstrate that these homeodomain proteins appear to have a key role in the establishment and development of the gametophyte and sporophyte phases of V. speciosa lifecycle, as well as in the control of the transition between both phases. Vandenboschia speciosa VsKNAT3 (a KNOX2 class protein) as well as VsBELL4 and VsBELL10 proteins have higher expression levels during the sporophyte program. On the contrary, one V. speciosa KNOX1 protein (VsKNAT6) and one KNOX2 protein (VsKNAT4) seem important during the development of the gametophyte phase. TALE homeobox genes might be among the key regulators in the gametophyte-to-sporophyte developmental transition in regular populations that show alternation of generations, since some of the genes analyzed here (VsKNAT3, VsKNAT6, VsBELL4, and VsBELL6) are upregulated in a non-alternating population in which only independent gametophytes are found (they grow by vegetative reproduction outside of the range of sporophyte distribution). Thus, these four genes might trigger the vegetative propagation of the gametophyte and the repression of the sexual development in populations composed of independent gametophytes. This study represents a comprehensive

  16. Identification and Characterization of TALE Homeobox Genes in the Endangered Fern Vandenboschia speciosa.

    PubMed

    Ruiz-Estévez, Mercedes; Bakkali, Mohammed; Martín-Blázquez, Rubén; Garrido-Ramos, Manuel A

    2017-10-17

    We report and discuss the results of a quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of the expression patterns of seven three amino acid loop extension ( TALE ) homeobox genes (four KNOTTED-like homeobox ( KNOX ) and three BEL1-like homeobox ( BELL ) genes) identified after next generation sequencing (NGS) and assembly of the sporophyte and gametophyte transcriptomes of the endangered fern species Vandenboschia speciosa . Among the four KNOX genes, two belonged to the KNOX1 class and the other two belonged to the KNOX2 class. Analysis of the deduced amino acid sequences supported the typical domain structure of both types of TALE proteins, and the homology to TALE proteins of mosses, lycophytes, and seed plant species. The expression analyses demonstrate that these homeodomain proteins appear to have a key role in the establishment and development of the gametophyte and sporophyte phases of V. speciosa lifecycle, as well as in the control of the transition between both phases. Vandenboschia speciosa VsKNAT3 (a KNOX2 class protein) as well as VsBELL4 and VsBELL10 proteins have higher expression levels during the sporophyte program. On the contrary, one V. speciosa KNOX1 protein (VsKNAT6) and one KNOX2 protein (VsKNAT4) seem important during the development of the gametophyte phase. TALE homeobox genes might be among the key regulators in the gametophyte-to-sporophyte developmental transition in regular populations that show alternation of generations, since some of the genes analyzed here ( VsKNAT3 , VsKNAT6 , VsBELL4 , and VsBELL6 ) are upregulated in a non-alternating population in which only independent gametophytes are found (they grow by vegetative reproduction outside of the range of sporophyte distribution). Thus, these four genes might trigger the vegetative propagation of the gametophyte and the repression of the sexual development in populations composed of independent gametophytes. This study represents a comprehensive

  17. "Can Drama, through Icelandic Tales, Increase Children's Vocabulary"?

    ERIC Educational Resources Information Center

    Thorkelsdóttir, Rannveig Björk; Ragnarsdóttir, Ása Helga

    2013-01-01

    The article is based on a study, done by Ása Helga Ragnarsdóttir and Rannveig Björk Þorkelsdóttir in 2010-2011 were the authors explored the research question: Can drama, through Icelandic tales, increase children's vocabulary? Methodology of the study was quantitative approach (comparative research). Data was gathered through questionnaires and a…

  18. Using Fairy Tales for Critical Reading. Bonus Activity Book.

    ERIC Educational Resources Information Center

    Learning, 1991

    1991-01-01

    This activity book uses the whole language approach to encourage young readers and prereaders to become critical listeners and viewers by comparing different versions of familiar fairy tales ("The Three Little Pigs" and "Beauty and the Beast"). Class activities, educational games, posters, and student activity pages are…

  19. Programmable and highly resolved in vitro detection of 5-methylcytosine by TALEs.

    PubMed

    Kubik, Grzegorz; Schmidt, Moritz J; Penner, Johanna E; Summerer, Daniel

    2014-06-02

    Gene expression is extensively regulated by specific patterns of genomic 5-methylcytosine (mC), but the ability to directly detect this modification at user-defined genomic loci is limited. One reason is the lack of molecules that discriminate between mC and cytosine (C) and at the same time provide inherent, programmable sequence-selectivity. Programmable transcription-activator-like effectors (TALEs) have been observed to exhibit mC-sensitivity in vivo, but to only a limited extent in vitro. We report an mC-detection assay based on TALE control of DNA replication that displays unexpectedly strong mC-discrimination ability in vitro. The status and level of mC modification at single positions in oligonucleotides can be determined unambiguously by this assay, independently of the overall target sequence. Moreover, discrimination is reliably observed for positions bound by N-terminal and central regions of TALEs. This indicates the wide scope and robustness of the approach for highly resolved mC detection and enabled the detection of a single mC in a large, eukaryotic genome. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Social, Biological and Physical Meta-Mechanisms a tale of Tails

    NASA Astrophysics Data System (ADS)

    West, Bruce J.

    The tale concerns the uncertainty of knowledge in the natural, social and life sciences and the tails are associated with the statistical distributions and correlation functions describing these scientific uncertainties. The tails in many phenomena are mentioned, including the long-range correlations in DNA sequences, the longtime memory in human gait and heart beats, the patterns over time in the births of babies to teenagers, as well as in the sexual pairings of homosexual men, and the volatility in financial markets among many other exemplars. I shall argue that these phenomena are so complex that no one is able to understand them completely. However, insights and partial knowledge about such complex mechanistic understanding of the phenomena being studied. These strategies include the development of models, using the fractal stochastic processes, chaotic dynamical systems, and the fractional calculus; all of which are tied together, using the concept of scaling, and therein hangs the tale. The perspective adopted in this lecture is not the dogmatic presentation often found in text books, in large part because there is no "right answer" to the questions being posed. Rather than answers, there are clues, indications, suggestions and tracks in the snow, as there always are at the frontiers of science. Is is my perspective of this frontier that I will be presenting and which is laid out in detail in Physiology, Promiscuity and Prophecy at the Millennium: A Tale of Tails25.

  1. A novel mode of enhancer evolution: The Tal1 stem cell enhancer recruited a MIR element to specifically boost its activity

    PubMed Central

    Smith, Aileen M.; Sanchez, Maria-Jose; Follows, George A.; Kinston, Sarah; Donaldson, Ian J.; Green, Anthony R.; Göttgens, Berthold

    2008-01-01

    Altered cis-regulation is thought to underpin much of metazoan evolution, yet the underlying mechanisms remain largely obscure. The stem cell leukemia TAL1 (also known as SCL) transcription factor is essential for the normal development of blood stem cells and we have previously shown that the Tal1 +19 enhancer directs expression to hematopoietic stem cells, hematopoietic progenitors, and to endothelium. Here we demonstrate that an adjacent region 1 kb upstream (+18 element) is in an open chromatin configuration and carries active histone marks but does not function as an enhancer in transgenic mice. Instead, it boosts activity of the +19 enhancer both in stable transfection assays and during differentiation of embryonic stem (ES) cells carrying single-copy reporter constructs targeted to the Hprt locus. The +18 element contains a mammalian interspersed repeat (MIR) which is essential for the +18 function and which was transposed to the Tal1 locus ∼160 million years ago at the time of the mammalian/marsupial branchpoint. Our data demonstrate a previously unrecognized mechanism whereby enhancer activity is modulated by a transposon exerting a “booster” function which would go undetected by conventional transgenic approaches. PMID:18687876

  2. Construct Validation of the Fairy Tale Test--Standardization Data.

    ERIC Educational Resources Information Center

    Coulacoglou, Carina

    2002-01-01

    Studied the construct validity of the Fairy Tale Test (C. Coulacoglu, 1993), a personality projective test for children, in a sample of 800 Greek children aged 8, 10, and 12. Factor analysis led to identification of eight primary factors, and correlations with other measures provide construct validity evidence. (SLD)

  3. HOX and TALE signatures specify human stromal stem cell populations from different sources.

    PubMed

    Picchi, Jacopo; Trombi, Luisa; Spugnesi, Laura; Barachini, Serena; Maroni, Giorgia; Brodano, Giovanni Barbanti; Boriani, Stefano; Valtieri, Mauro; Petrini, Mario; Magli, Maria Cristina

    2013-04-01

    Human stromal stem cell populations reside in different tissues and anatomical sites, however a critical question related to their efficient use in regenerative medicine is whether they exhibit equivalent biological properties. Here, we compared cellular and molecular characteristics of stromal stem cells derived from the bone marrow, at different body sites (iliac crest, sternum, and vertebrae) and other tissues (dental pulp and colon). In particular, we investigated whether homeobox genes of the HOX and TALE subfamilies might provide suitable markers to identify distinct stromal cell populations, as HOX proteins control cell positional identity and, together with their co-factors TALE, are involved in orchestrating differentiation of adult tissues. Our results show that stromal populations from different sources, although immunophenotypically similar, display distinct HOX and TALE signatures, as well as different growth and differentiation abilities. Stromal stem cells from different tissues are characterized by specific HOX profiles, differing in the number and type of active genes, as well as in their level of expression. Conversely, bone marrow-derived cell populations can be essentially distinguished for the expression levels of specific HOX members, strongly suggesting that quantitative differences in HOX activity may be crucial. Taken together, our data indicate that the HOX and TALE profiles provide positional, embryological and hierarchical identity of human stromal stem cells. Furthermore, our data suggest that cell populations derived from different body sites may not represent equivalent cell sources for cell-based therapeutical strategies for regeneration and repair of specific tissues. Copyright © 2012 Wiley Periodicals, Inc.

  4. From Tales of the Tongue to Tales of the Pen: An Organic Approach to Children's Literature. Resource Guide. NEH 1989 Summer Institute.

    ERIC Educational Resources Information Center

    Southwest Texas State Univ., San Marcos. Dept. of English.

    Developed from the activities of a summer institute in Texas that focused on "The Odyssey," folk and fairy tale, and folk rhyme, this resource guide presents 50 lesson plans offering a variety of approaches to teaching mythology and folklore to elementary school students. The lesson plans presented in the resource guide share a common…

  5. A resistance locus in the American heirloom rice variety Carolina Gold Select is triggered by TAL effectors with diverse predicted targets and is effective against African strains of Xanthomonas oryzae pv. oryzicola.

    PubMed

    Triplett, Lindsay R; Cohen, Stephen P; Heffelfinger, Christopher; Schmidt, Clarice L; Huerta, Alejandra I; Tekete, Cheick; Verdier, Valerie; Bogdanove, Adam J; Leach, Jan E

    2016-09-01

    The rice pathogens Xanthomonas oryzae pathovar (pv.) oryzae and pv. oryzicola produce numerous transcription activator-like (TAL) effectors that increase bacterial virulence by activating expression of host susceptibility genes. Rice resistance mechanisms against TAL effectors include polymorphisms that prevent effector binding to susceptibility gene promoters, or that allow effector activation of resistance genes. This study identifies, in the heirloom variety Carolina Gold Select, a third mechanism of rice resistance involving TAL effectors. This resistance manifests through strong suppression of disease development in response to diverse TAL effectors from both X. oryzae pathovars. The resistance can be triggered by an effector with only 3.5 central repeats, is independent of the composition of the repeat variable di-residues that determine TAL effector binding specificity, and is independent of the transcriptional activation domain. We determined that the resistance is conferred by a single dominant locus, designated Xo1, that maps to a 1.09 Mbp fragment on chromosome 4. The Xo1 interval also confers complete resistance to the strains in the African clade of X. oryzae pv. oryzicola, representing the first dominant resistance locus against bacterial leaf streak in rice. The strong phenotypic similarity between the TAL effector-triggered resistance conferred by Xo1 and that conferred by the tomato resistance gene Bs4 suggests that monocots and dicots share an ancient or convergently evolved mechanism to recognize analogous TAL effector epitopes. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  6. A resistance locus in the American heirloom rice variety Carolina Gold Select is triggered by TAL effectors with diverse predicted targets and is effective against African strains of Xanthomonas oryzae pv. oryzicola

    PubMed Central

    Triplett, Lindsay R.; Cohen, Stephen P.; Heffelfinger, Christopher; Schmidt, Clarice L.; Huerta, Alejandra; Tekete, Cheick; Verdier, Valerie; Bogdanove, Adam J.; Leach, Jan E.

    2016-01-01

    Summary The rice pathogens Xanthomonas oryzae pathovar (pv.) oryzae and pv. oryzicola produce numerous transcription activator-like (TAL) effectors that increase bacterial virulence by activating expression of host susceptibility genes. Rice resistance mechanisms against TAL effectors include polymorphisms that prevent effector binding to susceptibility gene promoters, or that allow effector activation of resistance genes. This study identifies, in the heirloom variety Carolina Gold Select, a third mechanism of rice resistance involving TAL effectors. This resistance manifests through strong suppression of disease development in response to diverse TAL effectors from both X. oryzae pathovars. The resistance can be triggered by an effector with only 3.5 central repeats, is independent of the composition of the repeat variable diresidues that determine TAL effector binding specificity, and is independent of the transcriptional activation domain. We determined that the resistance is conferred by a single dominant locus, designated Xo1, that maps to a 1.09 Mbp fragment on chromosome 4. The Xo1 interval also confers complete resistance to the strains in the African clade of X. oryzae pv. oryzicola, representing the first dominant resistance locus against bacterial leaf streak in rice. The strong phenotypic similarity between the TAL effector triggered resistance conferred by Xo1 and that conferred by the tomato resistance gene Bs4 suggests that monocots and dicots share an ancient or convergently evolved mechanism to recognize analogous TAL effector epitopes. PMID:27197779

  7. Engineering and Application of Zinc Finger Proteins and TALEs for Biomedical Research.

    PubMed

    Kim, Moon-Soo; Kini, Anu Ganesh

    2017-08-01

    Engineered DNA-binding domains provide a powerful technology for numerous biomedical studies due to their ability to recognize specific DNA sequences. Zinc fingers (ZF) are one of the most common DNA-binding domains and have been extensively studied for a variety of applications, such as gene regulation, genome engineering and diagnostics. Another novel DNA-binding domain known as a transcriptional activator-like effector (TALE) has been more recently discovered, which has a previously undescribed DNA-binding mode. Due to their modular architecture and flexibility, TALEs have been rapidly developed into artificial gene targeting reagents. Here, we describe the methods used to design these DNA-binding proteins and their key applications in biomedical research.

  8. Once upon a Tale. 1995 Florida Library Youth Program.

    ERIC Educational Resources Information Center

    Abramoff, Carolann Palm, Comp.; And Others

    The Florida Library Youth Program is an extension of the Florida Summer Library Program. Many libraries have wanted to provide programs for school-age children at times other than the traditional summer vacation, and this guide responds to their needs. The theme, "Once Upon a Tale," focuses on folklore, stories, and storytelling. The…

  9. Generation of TALE nickase-mediated gene-targeted cows expressing human serum albumin in mammary glands.

    PubMed

    Luo, Yan; Wang, Yongsheng; Liu, Jun; Cui, Chenchen; Wu, Yongyan; Lan, Hui; Chen, Qi; Liu, Xu; Quan, Fusheng; Guo, Zekun; Zhang, Yong

    2016-02-08

    Targeting exogenous genes at milk protein loci via gene-targeting technology is an ideal strategy for producing large quantities of pharmaceutical proteins. Transcription-activator-like effector (TALE) nucleases (TALENs) are an efficient genome-editing tool. However, the off-target effects may lead to unintended gene mutations. In this study, we constructed TALENs and TALE nickases directed against exon 2 of the bovine β-lactoglobulin (BLG) locus. The nickases can induce a site-specific DNA single-strand break, without inducing double-strand break and nonhomologous end joining mediated gene mutation, and lower cell apoptosis rate than TALENs. After co-transfecting the bovine fetal fibroblasts with human serum albumin (HSA) gene-targeting vector and TALE nickase expression vectors, approximately 4.8% (40/835) of the cell clones contained HSA at BLG locus. Unexpectedly, one homozygous gene-targeted cell clone (1/835, 0.1%) was obtained by targeting both alleles of BLG in a single round of transfection. The recombinant protein mimicking the endogenous BLG was highly expressed and correctly folded in the mammary glands of the targeted cows, and the expression level of HSA was significantly increased in the homozygous targeted cows. Results suggested that the combination of TALE nickase-mediated gene targeting and somatic cell nuclear transfer is a feasible and safe approach in producing gene-targeted livestock.

  10. Xanthomonas oryzae pv. oryzae TALE proteins recruit OsTFIIAγ1 to compensate for the absence of OsTFIIAγ5 in bacterial blight in rice.

    PubMed

    Ma, Wenxiu; Zou, Lifang; Ji, Zhiyuan; Xu, Xiameng; Xu, Zhengyin; Yang, Yangyang; Alfano, James R; Chen, Gongyou

    2018-04-28

    Xanthomonas oryzae pv. oryzae (Xoo), causal agent of bacterial blight (BB) of rice, uses transcription activator-like effectors (TALEs) to interact with the basal transcription factor gama subunit OsTFIIAγ5 (Xa5) and activates transcription of host genes. However, how OsTFIIAγ1, the other OsTFIIAγ protein, functions in the presence of TALEs remains unclear. In this study, we show that OsTFIIAγ1 plays a compensatory role in the absence of Xa5. The expression of OsTFIIAγ1, which is activated by TALE PthXo7, increased the expression of host genes targeted by avirulent and virulent TALEs. Defective OsTFIIAγ1 rice lines showed reduced expression of the TALE-targeted susceptibility (S) genes, OsSWEET11 and OsSWEET14, which resulted in increased BB resistance. Selected TALEs (PthXo1, AvrXa7, and AvrXa27) were evaluated for interactions with OsTFIIAγ1, Xa5 and xa5 (naturally-occurring mutant form of Xa5) using biomolecular fluorescence complementation (BiFC) and microscale thermophoresis (MST). BiFC and MST demonstrated that the three TALEs bind Xa5 and OsTFIIAγ1 with a stronger affinity than xa5. These results provide insight into the complex roles of OsTFIIAγ1 and OsTFIIAγ5 in TALE-mediated host gene transcription. This article is protected by copyright. All rights reserved. © 2018 BSPP and John Wiley & Sons Ltd.

  11. Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood, a new chemotype from Montenegro.

    PubMed

    Garzoli, Stefania; Božović, Mijat; Baldisserotto, Anna; Andreotti, Elisa; Pepi, Federico; Tadić, Vanja; Manfredini, Stefano; Ragno, Rino

    2018-05-01

    A study on essential oil fractions of the Western Balkan endemic Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood collected in Montenegro is reported. The 24-h systematic steam distillation extraction procedure was performed. The gas chromatographic/mass spectrometric (GC/MS) analysis of the fractions showed γ-elemene and spathulenol as two main constituents, revealing a new chemotype of this plant species. Although varying in the content of these two main compounds, which makes the fractions quite different between each other, evaluation of the anti-Candida activity showed the lack of any significant efficacy.

  12. OGS improvements in the year 2011 in running the Northeastern Italy Seismic Network

    NASA Astrophysics Data System (ADS)

    Bragato, P. L.; Pesaresi, D.; Saraò, A.; Di Bartolomeo, P.; Durı, G.

    2012-04-01

    The Centro di Ricerche Sismologiche (CRS, Seismological Research Center) of the Istituto Nazionale di Oceanografia e di Geofisica Sperimentale (OGS, Italian National Institute for Oceanography and Experimental Geophysics) in Udine (Italy) after the strong earthquake of magnitude M=6.4 occurred in 1976 in the Italian Friuli-Venezia Giulia region, started to operate the Northeastern Italy Seismic Network: it currently consists of 15 very sensitive broad band and 21 simpler short period seismic stations, all telemetered to and acquired in real time at the OGS-CRS data center in Udine. Real time data exchange agreements in place with other Italian, Slovenian, Austrian and Swiss seismological institutes lead to a total number of about 100 seismic stations acquired in real time, which makes the OGS the reference institute for seismic monitoring of Northeastern Italy. Since 2002 OGS-CRS is using the Antelope software suite on several workstations plus a SUN Cluster as the main tool for collecting, analyzing, archiving and exchanging seismic data, initially in the framework of the EU Interreg IIIA project "Trans-national seismological networks in the South-Eastern Alps". SeisComP is also used as a real time data exchange server tool. In order to improve the seismological monitoring of the Northeastern Italy area, at OGS-CRS we tuned existing programs and created ad hoc ones like: a customized web server named PickServer to manually relocate earthquakes, a script for automatic moment tensor determination, scripts for web publishing of earthquake parametric data, waveforms, state of health parameters and shaking maps, noise characterization by means of automatic spectra analysis, and last but not least scripts for email/SMS/fax alerting. The OGS-CRS Real Time Seismological website (RTS, http://rts.crs.inogs.it/) operative since several years was initially developed in the framework of the Italian DPC-INGV S3 Project: the RTS website shows classic earthquake locations

  13. Aesop and Company: Using Traditional Tales in EFL Classes.

    ERIC Educational Resources Information Center

    Allen, Virginia French

    Making repeated use of a traditional tale can offer various kinds of language practice. Many new teachers use a reading passage just once, investing considerable time in the explanation of the vocabulary needed to understand it, and then rush on to something new. Actually, the best potentialities of the material are still to be tapped, through…

  14. Shamans and Kushtakas: North Coast Tales of the Supernatural.

    ERIC Educational Resources Information Center

    Beck, Mary Giraudo

    The Tlingit and Haida are Native Americans who inhabit southeast Alaska and share many traditions and stories. Written by a non-native scholar, this book contains nine Tlingit and Haida tales concerned with shamans and kushtakas. Land otters were fearful hybrid beings of the spirit world. Able to live on land and in water, they had the special…

  15. Understanding the Psychology of a Trickster Tale: 5-Year-Old Japanese Kindergarten Children Collaboratively Retelling a "Kitsune" Story

    ERIC Educational Resources Information Center

    Oshiro, Aiko; Pihl, Agneta; Peterson, Louise; Pramling, Niklas

    2017-01-01

    How children understand the psychology of a story (i.e., the intentions and experiences of its characters) is pivotal to comprehending its point. In this study we investigate empirically how 5-year-old children in a Japanese kindergarten manage mental state verbs and adjectives when collaboratively retelling a tale heard. The tale, an example of a…

  16. Spectrum measurement with the Telescope Array Low Energy Extension (TALE) fluorescence detector

    NASA Astrophysics Data System (ADS)

    Zundel, Zachary James

    The Telescope Array (TA) experiment is the largest Ultra High Energy cosmic ray observatory in the northern hemisphere and is designed to be sensitive to cosmic ray air showers above 1018eV. Despite the substantial measurements made by TA and AUGER (the largest cosmic ray observatory in the southern hemisphere), there remains uncertainty about whether the highest energy cosmic rays are galactic or extragalactic in origin. Locating features in the cosmic ray energy spectrum below 1018eV that indicate a transition from galactic to extragalactic sources would clarify the interpretation of measurements made at the highest energies. The Telescope Array Low Energy Extension (TALE) is designed to extend the energy threshold of the TA observatory down to 1016.5eV in order to make such measurements. This dissertation details the construction, calibration, and operation of the TALE flu- orescence detector. A measurement of the flux of cosmic rays in the energy range of 1016.5 -- 1018.5eV is made using the monocular data set taken between September 2013 and January 2014. The TALE fluorescence detector observes evidence for a softening of the cosmic spectrum at 1017.25+/-0.5eV. The evidence of a change in the spectrum motivates continued study of 1016.5 -- 1018.5eV cosmic rays.

  17. The ethics of heroism in medieval and American Indian tales.

    PubMed

    Scott, A

    1990-01-01

    Oral-traditional stories detail their heroes' growth through a narrative pattern of exile and return that places the heroes in situations repeatedly challenging their strength and resolve. Through the motif of the quest, medieval and American Indian tales alike reaffirm general psychological truths that bear upon our understanding of human nature. Stories about heroes are stories about us: about our desires to grow up, to defeat death, to prove ourselves in difficult situations, and to achieve recognition or admiration among our peers (Becker, 1973, p. 4). In this way, medieval and American Indian tales are about self-actualization. They maintain that "one has within oneself proclivity toward growth and unity of personality ... and an automatic thrust toward expression" of these qualities (Yalom, 1980, p. 9). All forms of literature, however, reflect ideas peculiar to their cultures. The ways in which these basic human truths are represented in medieval and American Indian tales suggest the differing religious or social concerns that have informed these truths and have given them shape. To a large degree, the medieval knight's view of "self" and "other" encompasses the view that Western humanity has had (and continues to have) of itself. This is a view conditioned upon the superiority of the "self" as measured against the inferiority of the "other," reinforced through existing social (hierarchial) and religious (Judeo-Christian) codes of behavior. Such codes are not only inadequate to the task of interpreting American Indian perceptions of "self" and "other," they are inimical to the ethical foundation underlying them. Scott Momaday remarks that "you cannot understand how the Indian thinks of himself in relation to the world around him unless you understand his conception of what is appropriate; particularly what is morally appropriate within the context of that relationship" (Basso, 1984, p. 46). For the American Indian hero, self-actualization is self

  18. The Fairy-Folk Tale in Media Art: Reflections of Disney and Duvall.

    ERIC Educational Resources Information Center

    Molloy, Toni

    1988-01-01

    Focuses on Walt Disney and Shelley Duvall, mass media producers who furnish children with fairy-folklore. Compares and contrasts what Disney and Duvall do and do not convey through their fairy-folk tales. (MS)

  19. Effects of anion transport inhibitors and ion substitution on Cl sup minus transport in TAL of Henle's loop

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

    Kondo, Yoshiaki; Yoshitomi, Koji; Imai, Masashi

    1987-12-01

    To identify the mechanism of Cl{sup {minus}} transport across the thin ascending limb of Henle's loop (TAL), the authors examined effects of anion transport inhibitors and ionic substitution in the isolated segments of hamsters using the in vitro microperfusion technique. 4,4{prime}-diisothiocyanostilbene-2,2{prime}-disulfonic acid (DIDS) at 10{sup {minus}3} M changed the NaCl diffusion voltage (V{sub t}) to the orientation that corresponds to the decrease in the Cl{sup {minus}}-Na{sup +} permeability ratio when it was added either to the bath or to the lumen. DIDS, added to the bath or to the lumen decreased the lumen-to-bath flux coefficient for {sup 36}Cl, whereas itmore » had little effect on the flux coefficient for {sup 22}Na. The inhibitory effect of phloretin was rapid and reversible. Phloridzin was ineffective. From these observations, they conclude that Cl{sup {minus}} transport across the TAL is distinct from Na{sup +} and is not coupled with Na{sup +}, K{sup +}, or HCO{sup {minus}}{sub 3}.« less

  20. Telling Tales over Time: Constructing and Deconstructing the School Calendar

    ERIC Educational Resources Information Center

    Weiss, Joel; Brown, Robert S.

    2003-01-01

    The September-to-June school calendar has been a fixture of North America for almost a century. Its origins have usually been told as an unexamined tale attributed to features of nineteenth century rural society. We challenge this interpretation by suggesting that multiple pressures arising from increasing urbanization influenced its roots. We…

  1. Location Capability and Site Characterization Installing a Borehole VBB Seismometer: the OGS Experience in Ferrara (Italy)

    NASA Astrophysics Data System (ADS)

    Pesaresi, D.; Barnaba, C.

    2014-12-01

    The Centro di Ricerche Sismologiche (CRS, Seismological Research Centre) of the Istituto Nazionale di Oceanografia e di Geofisica Sperimentale (OGS, Italian National Institute for Oceanography and Experimental Geophysics) in Udine (Italy) after the strong earthquake of magnitude M=6.4 occurred in 1976 in the Italian Friuli-Venezia Giulia region, started to operate the Northeastern Italy Seismic Network: it currently consists of 19 very sensitive broad band and 17 simpler short period seismic stations, all telemetered to and acquired in real time at the OGS CRS data centre in Udine. The southwestern edge of the OGS seismic network stands on the Po alluvial basin: earthquake localization and characterization in this area is affected by the presence of soft alluvial deposits. Following the ML=5.9 earthquake that struck the Emilia region around Ferrara in Northern Italy on May 20, 2012, a cooperation of Istituto Nazionale di Geofisica e Vulcanologia, OGS, the Comune di Ferrara and the University of Ferrara lead to the reinstallation of a previously existing very broad band (VBB) borehole seismic station in Ferrara and to the deployment of a temporary seismographic network consisting of eight portable seismological stations, to record the local earthquakes that occurred during the seismic sequence. The aim of the OGS intervention was on one hand to extend its real time seismic monitoring capabilities toward South-West, including Ferrara and its surroundings, and on the other hand to evaluate seismic site responses in the area. We will introduce details of the Ferrara VBB borehole station and the OGS temporary seismographic network configuration and installation. We will then illustrate the location capability performances, and finally we will shortly describe seismic site characterization with surface/borehole comparisons in terms of seismic noise, site amplification and resonance frequencies.

  2. Fairy tales: a compass for children's healthy development--a qualitative study in a Greek island.

    PubMed

    Tsitsani, P; Psyllidou, S; Batzios, S P; Livas, S; Ouranos, M; Cassimos, D

    2012-03-01

    Fairy tales have always been an integrated part of children's everyday life. In our days, they still represent important ways of helping the children share their desires and express their agonies and inner conflicts. The present descriptive qualitative study aims to describe parents' opinions and children's preferences regarding storytelling. Four hundred and seventy parents took part in the study and were interviewed following a semi-structured guide with open-ended trigger questions. Data were processed via content analysis methods. Three main themes were constructed. The vast majority of interviewees acknowledged their strong belief in the power of fairy tales and stated that their children listen to stories at least once a week. Most of them use storytelling as an instructive tool, in order to soothe their children's anxieties or set examples for them. Concerning children's preferences, the majority of them choose classic fairy tales over modern ones with Little Red Riding Hood taking precedence over other famous stories. All participants acknowledged the fact that their children are amused and positively affected by storytelling, while young readers share their enthusiasm for fairy tales in many ways, mostly by talking about their favourite character. Finally, in relation to the villains, children seem to be satisfied or relieved when they are punished and only a small number of participants stated that the cruel punishment of bad characters creates feelings of fear to their kids. The findings of this study emphasize the crucial role that storytelling plays in children's life and normal development. © 2011 Blackwell Publishing Ltd.

  3. OGS improvements in 2012 in running the Northeastern Italy Seismic Network: the Ferrara VBB borehole seismic station

    NASA Astrophysics Data System (ADS)

    Pesaresi, Damiano; Romanelli, Marco; Barnaba, Carla; Bragato, Pier Luigi; Durì, Giorgio

    2013-04-01

    The Centro di Ricerche Sismologiche (CRS, Seismological Research Center) of the Istituto Nazionale di Oceanografia e di Geofisica Sperimentale (OGS, Italian National Institute for Oceanography and Experimental Geophysics) in Udine (Italy) after the strong earthquake of magnitude M=6.4 occurred in 1976 in the Italian Friuli-Venezia Giulia region, started to operate the Northeastern Italy Seismic Network: it currently consists of 17 very sensitive broad band and 18 simpler short period seismic stations, all telemetered to and acquired in real time at the OGS-CRS data center in Udine. Real time data exchange agreements in place with other Italian, Slovenian, Austrian and Swiss seismological institutes lead to a total number of about 100 seismic stations acquired in real time, which makes the OGS the reference institute for seismic monitoring of Northeastern Italy. The southwestern edge of the OGS seismic network stands on the Po alluvial basin: earthquake localization and characterization in this area is affected by the presence of soft alluvial deposits. OGS ha already experience in running a local seismic network in high noise conditions making use of borehole installations in the case of the micro-seismicity monitoring of a local gas storage site for a private company. Following the ML=5.9 earthquake that struck the Emilia region around Ferrara in Northern Italy on May 20, 2012 at 02:03:53 UTC, a cooperation of Istituto Nazionale di Geofisica e Vulcanologia, OGS, the Comune di Ferrara and the University of Ferrara lead to the reinstallation of a previously existing very broad band (VBB) borehole seismic station in Ferrara. The aim of the OGS intervention was on one hand to extend its real time seismic monitoring capabilities toward South-West, including Ferrara and its surroundings, and on the other hand to evaluate the seismic response at the site. We will describe improvements in running the Northeastern Italy Seismic Network, including details of the Ferrara VBB

  4. α decay properties of 297Og within the two-potential approach

    NASA Astrophysics Data System (ADS)

    Deng, Jun-Gang; Cheng, Jun-Hao; Zheng, Bo; Li, Xiao-Hua

    2017-12-01

    The α decay half-life of the unknown nucleus 297Og is predicted within the two-potential approach, and α preformation probabilities of 64 odd-A nuclei in the region of proton numbers 82 < Z < 126 and neutron numbers 152 < N < 184, from 251Cf to 295Og, are extracted. In addition, based on the latest experimental data, a new set of parameters for α preformation probabilities considering the shell effect and proton-neutron interaction are obtained. The predicted α decay half-life of 297Og is 0.16 ms within a factor of 4.97. The predicted spin and parity of the ground states for 269Sg, 285Fl and 293Lv are 3/2+, 3/2+ and 5/2+, respectively. Supported by National Natural Science Foundation of China (11205083, 11505100), Construct Program of the Key Discipline in Hunan Province, the Research Foundation of Education Bureau of Hunan Province, China (15A159), the Natural Science Foundation of Hunan Province, China (2015JJ3103, 2015JJ2121), the Innovation Group of Nuclear and Particle Physics in USC, the Shandong Province Natural Science Foundation, China (ZR2015AQ007) and Hunan Provincial Innovation Foundation For Postgraduate (CX2017B536)

  5. α decay properties of 296Og within the two-potential approach

    NASA Astrophysics Data System (ADS)

    Deng, Jun-Gang; Zhao, Jie-Cheng; Chen, Jiu-Long; Wu, Xi-Jun; Li, Xiao-Hua

    2018-04-01

    The present work is a continuation of our previous paper [J.-G. Deng, et al., Chin. Phys. C, 41: 124109 (2017)]. In the present work, the α decay half-life of the unknown nucleus 296Og is predicted within the two-potential approach and the hindrance factors of all 20 even-even nuclei in the same region as 296Og, i.e. proton number 82Og, are extracted. The prediction is 1.09 ms within a factor of 5.12. In addition, based on the latest experimental data, a new set of parameters of α decay hindrance factors for the even-even nuclei in this region, considering the shell effect and proton-neutron interaction, are obtained. Supported by National Natural Science Foundation of China (11205083, 11505100), the Construct Program of the Key Discipline in Hunan Province, the Research Foundation of Education Bureau of Hunan Province, China (15A159), the Natural Science Foundation of Hunan Province, China (2015JJ3103, 2015JJ2121), the Innovation Group of Nuclear and Particle Physics in USC, the Shandong Province Natural Science Foundation, China (ZR2015AQ007) and Hunan Provincial Innovation Foundation For Postgraduate (CX2017B536)

  6. Benchmarking of TALE- and CRISPR/dCas9-Based Transcriptional Regulators in Mammalian Cells for the Construction of Synthetic Genetic Circuits.

    PubMed

    Lebar, Tina; Jerala, Roman

    2016-10-21

    Transcriptional activator-like effector (TALE)- and CRISPR/Cas9-based designable recognition domains represent a technological breakthrough not only for genome editing but also for building designed genetic circuits. Both platforms are able to target rarely occurring DNA segments, even within complex genomes. TALE and dCas9 domains, genetically fused to transcriptional regulatory domains, can be used for the construction of engineered logic circuits. Here we benchmarked the performance of the two platforms, targeting the same DNA sequences, to compare their advantages for the construction of designed circuits in mammalian cells. Optimal targeting strands for repression and activation of dCas9-based designed transcription factors were identified; both platforms exhibited good orthogonality and were used to construct functionally complete NOR gates. Although the CRISPR/dCas9 system is clearly easier to construct, TALE-based activators were significantly stronger, and the TALE-based platform performed better, especially for the construction of layered circuits.

  7. Managing Biases in Product Development Teams: A Tale of Two Rocks

    ERIC Educational Resources Information Center

    Keene, Michael A.

    2017-01-01

    The management of product development teams is a challenging task, especially when success hinges on the ability to guide technical and nontechnical personnel through an effective decision-making process. The "Tale of Two Rocks" exercise illustrates how differing motivations and beliefs about new technologies can affect the decisions…

  8. Chaucer's Dantean Presentation of Time in The Canterbury Tales: Libra and the Moon

    NASA Astrophysics Data System (ADS)

    Osborn, Marijane

    In the last of his several chronographiæ — astronomically expressed descriptions of time — contained in The Canterbury Tales, Chaucer uses language that has led modern readers to believe that he is making elementary errors about the altitude of the Sun above the horizon and about the astrological relationship between Libra and the Moon. In this essay, I argue that the errors are ours, not his. If one reads the altitude of the Sun by means of Chaucer's observing instrument, the astrolabe, and — forgetting astrology — perceives the Moon's relationship to the sign/constellation of Libra as a real one much like Dante's similar image at the end of The Divine Comedy, both the astronomical and spiritual meanings of the passage in the Tales become clearer.

  9. Women's Oppressed and Disfigured Life in Margaret Atwood's the Handmaid's Tale

    ERIC Educational Resources Information Center

    Zarrinjooee, Bahman; Kalantarian, Shirin

    2017-01-01

    The present study attempts to analyze Margaret Atwood's (1939-) "The Handmaid's Tale" (1985) based on theories of feminist thinker, Simone de Beauvoir (1908-1986) and applies her theories presented in "The Second Sex" (1949) that leads to better apprehension of sex and gender. Beauvoir's ideology focuses mainly on the cultural…

  10. A Trickster Tale about Integrating Indigenous Knowledge in University-Based Programs

    ERIC Educational Resources Information Center

    Moore, Sylvia

    2012-01-01

    Written as a trickster tale and co-narrated by the researcher and a trickster figure (Crow), this writing considers the challenges of bringing traditional ecological knowledge to environmental studies and science programs. The researcher describes a project to raise and release salmon, which was collaboratively developed and carried out by members…

  11. 40 CFR 721.9530 - Bis(2,2,6,6-tetra-methyl-piper-idinyl) ester of cycloalkyl spir-o-ke-tal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-clo-alkyl spir-o-ke-tal (PMN P-88-0083) is subject to reporting under this section for the significant... may cause: systemic effects, eye irritation. (iii) Industrial, commercial, and consumer activities....125 (a), (b), (c), (d), (f), (g), (h), (i), and (k). (2) Limitations or revocation of certain...

  12. 40 CFR 721.9530 - Bis(2,2,6,6-tetra-methyl-piper-idinyl) ester of cycloalkyl spir-o-ke-tal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-clo-alkyl spir-o-ke-tal (PMN P-88-0083) is subject to reporting under this section for the significant... may cause: systemic effects, eye irritation. (iii) Industrial, commercial, and consumer activities....125 (a), (b), (c), (d), (f), (g), (h), (i), and (k). (2) Limitations or revocation of certain...

  13. OGS improvements in 2012 in running the North-eastern Italy Seismic Network: the Ferrara VBB borehole seismic station

    NASA Astrophysics Data System (ADS)

    Pesaresi, D.; Romanelli, M.; Barnaba, C.; Bragato, P. L.; Durì, G.

    2014-07-01

    The Centro di Ricerche Sismologiche (CRS, Seismological Research Centre) of the Istituto Nazionale di Oceanografia e di Geofisica Sperimentale (OGS, Italian National Institute for Oceanography and Experimental Geophysics) in Udine (Italy) after the strong earthquake of magnitude M=6.4 occurred in 1976 in the Italian Friuli-Venezia Giulia region, started to operate the North-eastern Italy Seismic Network: it currently consists of 17 very sensitive broad band and 18 simpler short period seismic stations, all telemetered to and acquired in real time at the OGS-CRS data centre in Udine. Real time data exchange agreements in place with other Italian, Slovenian, Austrian and Swiss seismological institutes lead to a total number of about 100 seismic stations acquired in real time, which makes the OGS the reference institute for seismic monitoring of North-eastern Italy. The south-western edge of the OGS seismic network (Fig. 1) stands on the Po alluvial basin: earthquake localization and characterization in this area is affected by the presence of soft alluvial deposits. OGS ha already experience in running a local seismic network in high noise conditions making use of borehole installations in the case of the micro-seismicity monitoring of a local gas storage site for a private company. Following the ML = 5.9 earthquake that struck the Emilia region around Ferrara in Northern Italy on 20 May 2012 at 02:03:53 UTC, a cooperation of Istituto Nazionale di Geofisica e Vulcanologia, OGS, the Comune di Ferrara and the University of Ferrara lead to the reinstallation of a previously existing very broad band (VBB) borehole seismic station in Ferrara. The aim of the OGS intervention was on one hand to extend its real time seismic monitoring capabilities toward South-West, including Ferrara and its surroundings, and on the other hand to evaluate the seismic response at the site. We will describe improvements in running the North-eastern Italy Seismic Network, including details of

  14. From DNA binding to transcriptional activation: Is the TALE complete?

    PubMed

    Bobola, Nicoletta

    2017-09-04

    How transcription factors (TFs) control enhancer and promoter functions to effect changes in gene expression is an important question. In this issue, Hau et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201701154) show that the TALE TF MEIS recruits the histone modifier PARP1/ARTD1 at promoters to decompact chromatin and activate transcription. © 2017 Bobola.

  15. Creating a monomeric endonuclease TALE-I-SceI with high specificity and low genotoxicity in human cells.

    PubMed

    Lin, Jianfei; Chen, He; Luo, Ling; Lai, Yongrong; Xie, Wei; Kee, Kehkooi

    2015-01-01

    To correct a DNA mutation in the human genome for gene therapy, homology-directed repair (HDR) needs to be specific and have the lowest off-target effects to protect the human genome from deleterious mutations. Zinc finger nucleases, transcription activator-like effector nuclease (TALEN) and CRISPR-CAS9 systems have been engineered and used extensively to recognize and modify specific DNA sequences. Although TALEN and CRISPR/CAS9 could induce high levels of HDR in human cells, their genotoxicity was significantly higher. Here, we report the creation of a monomeric endonuclease that can recognize at least 33 bp by fusing the DNA-recognizing domain of TALEN (TALE) to a re-engineered homing endonuclease I-SceI. After sequentially re-engineering I-SceI to recognize 18 bp of the human β-globin sequence, the re-engineered I-SceI induced HDR in human cells. When the re-engineered I-SceI was fused to TALE (TALE-ISVB2), the chimeric endonuclease induced the same HDR rate at the human β-globin gene locus as that induced by TALEN, but significantly reduced genotoxicity. We further demonstrated that TALE-ISVB2 specifically targeted at the β-globin sequence in human hematopoietic stem cells. Therefore, this monomeric endonuclease has the potential to be used in therapeutic gene targeting in human cells. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Effect of pH on Cl sup minus transport in TAL of Henle's loop

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

    Kondo, Yoshiaki; Yoshitomi, Koji; Imai, Masashi

    1987-12-01

    To further characterize the mechanism of Cl{sup {minus}} transport across the hamster thin ascending limb (TAL) of Henle's loop, the authors examined effects of pH on Cl{sup {minus}} permeability as determined by either the choline chloride diffusion voltage or the lumen-to-bath {sup 36}Cl flux in the isolated segments perfused in vitro. When pH of the bathing fluid or the perfusate was reduced from 7.4 to 5.8, the Cl{sup {minus}}-Na{sup +} permeability ratio was reduced from 2.77 {plus minus} 0.21 to 0.48 {plus minus} 0.02 or from 2.55 {plus minus} 0.15 to 0.81 {plus minus} 0.11, respectively. At 37{degree}C, when themore » pH of the bathing fluid was reduced from 7.4 to 6.2, the lumen-to-bath flux coefficient for {sup 36}Cl was reduced from 84.8 {plus minus} 7.5 to 20.4 {plus minus} 3.2, whereas the value for {sup 22}Na was unchanged. From the pH titration curves for P{sub Cl}/P{sub Na}, pK{sub a} values for proton binding were 6.31 and 5.78, and Hill's coefficients were 2.1 and 2.3 on the basolateral side and on the luminal side, respectively. Intracellular acidification with o-nitrophenylacetate also decreased the Cl{sup {minus}} permeability. They conclude that (1) Cl{sup {minus}} transport across the TAL is mediated by a process that is sensitive to ambient pH, (2) the basolateral side is more sensitive to pH, (3) the proton binding exhibits positive cooperativity in the modulation of Cl{sup {minus}} transport, and (4) intracellular pH might also modulate Cl{sup {minus}} transport.« less

  17. Coyote & Little Turtle = Iisaw Niqw Yongosonhoya: A Traditional Hopi Tale and Coyote & the Winnowing Birds = Iisaw Niqw Tsaayantotaqam Tsiroot: A Traditional Hopi Tale. Original Language Series.

    ERIC Educational Resources Information Center

    Sekaquaptewa, Emory, Ed.; Pepper, Barbara, Ed.

    Intended to promote the preservation of the Hopi language, two illustrated children's books present traditional Hopi tales in bilingual format. Based on a story told by Herschel Talashoema, "Coyote & Little Turtle" tells how Little Turtle tricked Coyote into carrying him from the hot sand that burned his feet to Little Turtle's home in a spring.…

  18. Stories for the Campfire: A Collection of Memorable Tales for Camp.

    ERIC Educational Resources Information Center

    Hanson, Bob, Ed.; Roemmich, Bill, Ed.

    This book offers 46 children's camp stories, including stories about ghosts, adventure, other lands, humor, Indian fables, and stories with a moral. An introduction offers some background of the publication and a few tips on successful story-telling. The stories include: A Full Meal; A Fuzzy Tale; An Ameri-Indian's Ecological Lament and Prophecy;…

  19. "Tales from the Brazilian Jungle": Antonio Rocha, Storyteller. Cue Sheet for Teachers.

    ERIC Educational Resources Information Center

    Rees, Elizabeth

    This performance guide is designed for teachers to use with students before and after a performance of "Tales from the Brazilian Jungle" with storyteller Antonio Rocha. The guide, called a "Cuesheet," contains four sheets for use in class. The first, "About the Performance," prepares students for understanding…

  20. The Terminal: a tale of virtue.

    PubMed

    Austin, Wendy

    2007-01-01

    The movie, The terminal, is used to illustrate MacIntyre's description of virtue ethics. The terminal is a mythical tale about a traveler, Viktor Navorski, who is stranded by circumstances in a New York airport. Viktor is a person who, without a strict reliance on duty or rules, has developed the disposition to act well despite variation in his circumstances. His character is revealed in contrast to that of three other characters: a cleaner, a flight attendant and the airport manager. Stories like this one may be a good way to open dialogue among clinicians about being virtuous as a practitioner. Such dialogue may make striving to be virtuous an acceptable goal for practitioners and less like an idealistic, pseudo-goal for those aiming for sainthood.

  1. Escape from Management Hell: 12 Tales of Horror, Humor, and Heroism.

    ERIC Educational Resources Information Center

    Gilbreath, Robert D.

    This book offers a set of stories in which corporate executives demonstrate the folly and futility of their own business practices. In the stories, 12 executives are trying to escape from a hell of their own making. The tales provide insights into the management woes with which people at all levels deal on a daily basis. Topics include: the…

  2. Researcher Tales and Research Ethics: The Spaces in Which We Find Ourselves

    ERIC Educational Resources Information Center

    White, Julie; Fitzgerald, Tanya

    2010-01-01

    The tales we tell here focus on the ethical issues arising from our research practice with vulnerable young participants and those for whom research has been inextricably linked with European imperialism and colonialism. The importance of relational obligations, temporality and potential for a continuing narrative approach to ethical research…

  3. A Fairy-Tale Landscape

    NASA Technical Reports Server (NTRS)

    2008-01-01

    [figure removed for brevity, see original site] Click on image for animation

    Fun, fairy-tale nicknames have been assigned to features in this animated view of the workspace reachable by the robotic arm of NASA's Phoenix Mars Lander. For example, 'Sleepy Hollow' denotes a trench and 'Headless' designates a rock.

    A 'National Park,' marked by purple text and a purple arrow, has been set aside for protection until scientists and engineers have tested the operation of the robotic scoop. First touches with the scoop will be to the left of the 'National Park' line.

    Scientists use such informal names for easy identification of features of interest during the mission.

    In this view, rocks are circled in yellow, other areas of interest in green. The images were taken by the lander's 7-foot mast camera, called the Surface Stereo Imager.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  4. TALE and Shape: How to Make a Leaf Different.

    PubMed

    Di Giacomo, Elisabetta; Iannelli, Maria Adelaide; Frugis, Giovanna

    2013-05-06

    The Three Amino acid Loop Extension (TALE) proteins constitute an ancestral superclass of homeodomain transcription factors conserved in animals, plants and fungi. In plants they comprise two classes, KNOTTED1-LIKE homeobox (KNOX) and BEL1-like homeobox (BLH or BELL, hereafter referred to as BLH), which are involved in shoot apical meristem (SAM) function, as well as in the determination and morphological development of leaves, stems and inflorescences. Selective protein-protein interactions between KNOXs and BLHs affect heterodimer subcellular localization and target affinity. KNOXs exert their roles by maintaining a proper balance between undifferentiated and differentiated cell state through the modulation of multiple hormonal pathways. A pivotal function of KNOX in evolutionary diversification of leaf morphology has been assessed. In the SAM of both simple- and compound-leafed seed species, downregulation of most class 1 KNOX (KNOX1) genes marks the sites of leaf primordia initiation. However, KNOX1 expression is re-established during leaf primordia development of compound-leafed species to maintain transient indeterminacy and morphogenetic activity at the leaf margins. Despite the increasing knowledge available about KNOX1 protein function in plant development, a comprehensive view on their downstream effectors remains elusive. This review highlights the role of TALE proteins in leaf initiation and morphological plasticity with a focus on recent advances in the identification of downstream target genes and pathways.

  5. The Monets, Van Goghs, and Renoirs of Science Education: Writing Impressionist Tales as a Strategy for Facilitating Prospective Teachers' Reflections on Science Experiences

    ERIC Educational Resources Information Center

    Bryan, Lynn A.; Tippins, Deborah J.

    2005-01-01

    A particularly useful pedagogical strategy for beginning a dialogue with prospective teachers about the ways in which their experiences and beliefs shape their development of professional knowledge is writing impressionist tales. Impressionist tales are a form of autobiography that portrays one highly personal perspective on a significant moment…

  6. An engineered tale-transcription factor rescues transcription of factor VII impaired by promoter mutations and enhances its endogenous expression in hepatocytes.

    PubMed

    Barbon, Elena; Pignani, Silvia; Branchini, Alessio; Bernardi, Francesco; Pinotti, Mirko; Bovolenta, Matteo

    2016-06-24

    Tailored approaches to restore defective transcription responsible for severe diseases have been poorly explored. We tested transcription activator-like effectors fused to an activation domain (TALE-TFs) in a coagulation factor VII (FVII) deficiency model. In this model, the deficiency is caused by the -94C > G or -61T > G mutation, which abrogate the binding of Sp1 or HNF-4 transcription factors. Reporter assays in hepatoma HepG2 cells naturally expressing FVII identified a single TALE-TF (TF4) that, by targeting the region between mutations, specifically trans-activated both the variant (>100-fold) and wild-type (20-40-fold) F7 promoters. Importantly, in the genomic context of transfected HepG2 and transduced primary hepatocytes, TF4 increased F7 mRNA and protein levels (2- to 3-fold) without detectable off-target effects, even for the homologous F10 gene. The ectopic F7 expression in renal HEK293 cells was modestly affected by TF4 or by TALE-TF combinations. These results provide experimental evidence for TALE-TFs as gene-specific tools useful to counteract disease-causing promoter mutations.

  7. TALE nickase-mediated SP110 knockin endows cattle with increased resistance to tuberculosis.

    PubMed

    Wu, Haibo; Wang, Yongsheng; Zhang, Yan; Yang, Mingqi; Lv, Jiaxing; Liu, Jun; Zhang, Yong

    2015-03-31

    Transcription activator-like effector nuclease (TALEN)-mediated genome modification has been applied successfully to create transgenic animals in various species, such as mouse, pig, and even monkey. However, transgenic cattle with gene knockin have yet to be created using TALENs. Here, we report site-specific knockin of the transcription activator-like effector (TALE) nickase-mediated SP110 nuclear body protein gene (SP110) via homologous recombination to produce tuberculosis-resistant cattle. In vitro and in vivo challenge and transmission experiments proved that the transgenic cattle are able to control the growth and multiplication of Mycobacterium bovis, turn on the apoptotic pathway of cell death instead of necrosis after infection, and efficiently resist the low dose of M. bovis transmitted from tuberculous cattle in nature. In this study, we developed TALE nickases to modify the genome of Holstein-Friesian cattle, thereby engineering a heritable genome modification that facilitates resistance to tuberculosis.

  8. Regulation of CCL2 expression by an upstream TALE homeodomain protein-binding site that synergizes with the site created by the A-2578G SNP.

    PubMed

    Page, Stephen H; Wright, Edward K; Gama, Lucio; Clements, Janice E

    2011-01-01

    CC Chemokine Ligand 2 (CCL2) is a potent chemoattractant produced by macrophages and activated astrocytes during periods of inflammation within the central nervous system. Increased CCL2 expression is correlated with disease progression and severity, as observed in pulmonary tuberculosis, HCV-related liver disease, and HIV-associated dementia. The CCL2 distal promoter contains an A/G polymorphism at position -2578 and the homozygous -2578 G/G genotype is associated with increased CCL2 production and inflammation. However, the mechanisms that contribute to the phenotypic differences in CCL2 expression are poorly understood. We previously demonstrated that the -2578 G polymorphism creates a TALE homeodomain protein binding site (TALE binding site) for PREP1/PBX2 transcription factors. In this study, we identified the presence of an additional TALE binding site 22 bp upstream of the site created by the -2578 G polymorphism and demonstrated the synergistic effects of the two sites on the activation of the CCL2 promoter. Using chromatin immunoprecipitation (ChIP) assays, we demonstrated increased binding of the TALE proteins PREP1 and PBX2 to the -2578 G allele, and binding of IRF1 to both the A and G alleles. The presence of TALE binding sites that form inverted repeats within the -2578 G allele results in increased transcriptional activation of the CCL2 distal promoter while the presence of only the upstream TALE binding site within the -2578 A allele exerts repression of promoter activity.

  9. Efficient gene targeting by homology-directed repair in rat zygotes using TALE nucleases

    PubMed Central

    Remy, Séverine; Tesson, Laurent; Menoret, Séverine; Usal, Claire; De Cian, Anne; Thepenier, Virginie; Thinard, Reynald; Baron, Daniel; Charpentier, Marine; Renaud, Jean-Baptiste; Buelow, Roland; Cost, Gregory J.; Giovannangeli, Carine; Fraichard, Alexandre; Concordet, Jean-Paul; Anegon, Ignacio

    2014-01-01

    The generation of genetically modified animals is important for both research and commercial purposes. The rat is an important model organism that until recently lacked efficient genetic engineering tools. Sequence-specific nucleases, such as ZFNs, TALE nucleases, and CRISPR/Cas9 have allowed the creation of rat knockout models. Genetic engineering by homology-directed repair (HDR) is utilized to create animals expressing transgenes in a controlled way and to introduce precise genetic modifications. We applied TALE nucleases and donor DNA microinjection into zygotes to generate HDR-modified rats with large new sequences introduced into three different loci with high efficiency (0.62%–5.13% of microinjected zygotes). Two of these loci (Rosa26 and Hprt1) are known to allow robust and reproducible transgene expression and were targeted for integration of a GFP expression cassette driven by the CAG promoter. GFP-expressing embryos and four Rosa26 GFP rat lines analyzed showed strong and widespread GFP expression in most cells of all analyzed tissues. The third targeted locus was Ighm, where we performed successful exon exchange of rat exon 2 for the human one. At all three loci we observed HDR only when using linear and not circular donor DNA. Mild hypothermic (30°C) culture of zygotes after microinjection increased HDR efficiency for some loci. Our study demonstrates that TALE nuclease and donor DNA microinjection into rat zygotes results in efficient and reproducible targeted donor integration by HDR. This allowed creation of genetically modified rats in a work-, cost-, and time-effective manner. PMID:24989021

  10. Feigning terminal illness to get narcotics: a cautionary tale for hospices.

    PubMed

    Gonzalez, Faustino; Galante, Mirta

    2012-08-01

    We present the case of a woman who enrolled in the hospice benefit in order to obtain narcotics. We believe this is a cautionary tale for hospices because of our propensity to enroll patients with minimal corroborating information, in order not to delay symptom management. Also we are philosophically predisposed to believe a patient's self-report of pain and other distressing symptoms.

  11. Theoretical studies on the synthesis of SHE 290-302Og (Z=118) using 48Ca, 45Sc, 50Ti, 51V, 54Cr, 55Mn, 58Fe, 59Co and 64Ni induced reactions

    NASA Astrophysics Data System (ADS)

    Santhosh, K. P.; Safoora, V.

    2018-05-01

    Using the phenomenological model for production cross section (PMPC), the production cross sections for the synthesis of isotopes of superheavy element Og ( Z = 118) using the fusion reactions 48Ca+249-254Cf → 297-302Og, 45Sc+247,249Bk → 292,294Og, 50Ti + 242-248,250Cm → 292-298,300Og, 51V+241,243Am → 292,294Og, 54Cr + 238-242,244Pu → 292-296,298Og, 55Mn + 235-237Np → 290-292Og, 58Fe + 232-236, 238U → 290-294,296Og, 59Co + 231Pa → 290Og, and 64Ni + 228-230,232Cm → 292-294,296Og in xn (x=3,4,5) evaporation channel have been systematically studied at energies near and above the Coulomb barrier. We have predicted most suitable projectile-target combinations for the synthesis of isotopes 290-302Og among these reactions. Our calculated evaporation residue (ER) cross section values for the reaction 48Ca + 249Cf → 297Og is in excellent agreement with available experimental values. For the synthesis of Og, among all the reactions mentioned above, the 3n channel cross section (2458 fb) is larger for 48Ca + 251Cf → 299Og; 4n channel cross section (212 fb) is larger for 48Ca + 252Cf → 300Og and 5n channel cross section (34 fb) is larger for 48Ca + 253Cf → 301Og. The second largest 3n channel cross section (1143 fb) is obtained for the reaction, 50Ti + 245Cm → 295Og. Our studies will be useful for the future experiments to synthesize the isotopes of element Og which are not synthesized so far. We have also studied the effect of the use of mass values and shell correction of the Warsaw group which leads to a smaller ER cross section compared to the Moller group.

  12. Transient Tcf3 Gene Repression by TALE-Transcription Factor Targeting.

    PubMed

    Masuda, Junko; Kawamoto, Hiroshi; Strober, Warren; Takayama, Eiji; Mizutani, Akifumi; Murakami, Hiroshi; Ikawa, Tomokatsu; Kitani, Atsushi; Maeno, Narumi; Shigehiro, Tsukasa; Satoh, Ayano; Seno, Akimasa; Arun, Vaidyanath; Kasai, Tomonari; Fuss, Ivan J; Katsura, Yoshimoto; Seno, Masaharu

    2016-12-01

    Transplantation of hematopoietic stem and progenitor cells (HSCs) i.e., self-renewing cells that retain multipotentiality, is now a widely performed therapy for many hematopoietic diseases. However, these cells are present in low number and are subject to replicative senescence after extraction; thus, the acquisition of sufficient numbers of cells for transplantation requires donors able to provide repetitive blood samples and/or methods of expanding cell numbers without disturbing cell multipotentiality. Previous studies have shown that HSCs maintain their multipotentiality and self-renewal activity if TCF3 transcription function is blocked under B cell differentiating conditions. Taking advantage of this finding to devise a new approach to HSC expansion in vitro, we constructed an episomal expression vector that specifically targets and transiently represses the TCF3 gene. This consisted of a vector encoding a transcription activator-like effector (TALE) fused to a Krüppel-associated box (KRAB) repressor. We showed that this TALE-KRAB vector repressed expression of an exogenous reporter gene in HEK293 and COS-7 cell lines and, more importantly, efficiently repressed endogenous TCF3 in a human B lymphoma cell line. These findings suggest that this vector can be used to maintain multipotentiality in HSC being subjected to a long-term expansion regimen prior to transplantation.

  13. Drama Improvisation as a Method of Covering Fairy Tales in School Curriculum.

    ERIC Educational Resources Information Center

    Sefer, Jasmina; Angelovski, Nada

    In order to influence motivation and children's creativity, some attractive methods were introduced into the classical contents of the usual program of material (Serbocroatian) language and literature and other subjects in the curriculum planned for the third grade. Work on a tale was carried out in an atmosphere of slightly transformed space in…

  14. John Bauer: Painter of a Star-Spangled Fairy-Tale World

    NASA Astrophysics Data System (ADS)

    Sundin, M.; Roslund, C.

    Several generations of Swedish children have become acquainted with the world of fairy-tales through illustrations by the painter John Bauer in the Christmas magazine Goblins and Trolls. Next to his portrayal of grotesque but humorous trolls, his paintings of the Moon and the starry sky are among those best remembered. These pictures have inspired very many Swedes to take pleasure in the beauty of the stars and the movement of the Moon.

  15. Code-assisted discovery of TAL effector targets in bacterial leaf streak of rice reveals contrast with bacterial blight and a novel susceptibility gene

    USDA-ARS?s Scientific Manuscript database

    Transcription activator-like (TAL) effectors found in Xanthomonas spp. promote bacterial growth and plant susceptibility by binding specific DNA sequences or, effector-binding elements (EBEs), and inducing host gene expression. In this study, we have found substantially different transcriptional pro...

  16. Once upon anion: a tale of photodetachment.

    PubMed

    Lineberger, W Carl

    2013-01-01

    This contribution is very much a personal history of a journey through the wonderful world of anion chemistry, and a tale of how advances in laser technologies, theoretical methods, and computational capabilities continuously enabled advances in our understanding. It is a story of the excitement and joy that come from the opportunity to add to the fabric of science, and to do so by working as a group of excited explorers with common goals. The participants in this journey include me, my students and postdoctoral associates, my collaborators, and our many generous colleagues. It all happened, in the words of the Beatles, "with a little help from my friends." Actually, it was so much more than a little help!

  17. 'Le moment de la lune'. an auto-ethnographic tale of practice about menarche in a children's hospital.

    PubMed

    Denshire, Sally

    2011-08-01

    Auto-ethnographic accounts can highlight unsaid moments of professional practice. In this case, my auto-ethnographic tale 'Le moment de la lune' re-inscribes subjugated knowledge about menstruation and occupational therapy practice in the era before adolescent wards. This fictional tale is written in direct dialogue with an article that was published in this journal at a particular point in my own career as an occupational therapist. In the tale I am 'writing in' what was not written about in my article and in occupational therapy generally. This 'writing-in'/re-inscribing is the research method. My previous article 'Normal spaces' published in this journal in 1985, was organised around principles and generalities of youth-specific practice. The original article had little locating the personal or evoking the body and a heavy reliance on the literature. Issues of gender and culture were largely absent, or, perhaps, 'written out'. The corresponding tale of embodied sexuality, 'Le moment de la lune', articulates something of local complex practice and the particularity of individual therapeutic work to do with menstruation in self-care. Points of tension in 'Normal spaces' are elaborated and I explain how 'Le moment de la lune' problematises supporting menarche in a children's hospital. Now practice has moved on with dedicated adolescent wards in all major children's hospitals. Nevertheless, occupational therapy practice around issues of menstrual self-management is still under-documented. Writing about unspoken moments of practice can have ethical implications for expanding the ways occupational therapy practice can be written and understood. © 2011 The Author. Australian Occupational Therapy Journal © 2011 Occupational Therapy Australia.

  18. TALE nickase-mediated SP110 knockin endows cattle with increased resistance to tuberculosis

    PubMed Central

    Wu, Haibo; Wang, Yongsheng; Zhang, Yan; Yang, Mingqi; Lv, Jiaxing; Liu, Jun; Zhang, Yong

    2015-01-01

    Transcription activator-like effector nuclease (TALEN)-mediated genome modification has been applied successfully to create transgenic animals in various species, such as mouse, pig, and even monkey. However, transgenic cattle with gene knockin have yet to be created using TALENs. Here, we report site-specific knockin of the transcription activator-like effector (TALE) nickase-mediated SP110 nuclear body protein gene (SP110) via homologous recombination to produce tuberculosis-resistant cattle. In vitro and in vivo challenge and transmission experiments proved that the transgenic cattle are able to control the growth and multiplication of Mycobacterium bovis, turn on the apoptotic pathway of cell death instead of necrosis after infection, and efficiently resist the low dose of M. bovis transmitted from tuberculous cattle in nature. In this study, we developed TALE nickases to modify the genome of Holstein–Friesian cattle, thereby engineering a heritable genome modification that facilitates resistance to tuberculosis. PMID:25733846

  19. First Graders and Fairy Tales: One Teacher's Action Research of Critical Literacy

    ERIC Educational Resources Information Center

    Bourke, Ryan T.

    2008-01-01

    By using the fairy tale genre, one teacher was able to foster critical literacy in a first-grade classroom. By encouraging a critical perspective, the author reveals how the issues of identity, rules, and power were exposed to the students. The article also portrays how the author engaged in significant learning himself, realizing that to instill…

  20. The Turtle Went To War. Northern Cheyenne Folk Tales. Indian Culture Series.

    ERIC Educational Resources Information Center

    Tall Bull, Henry; Weist, Tom

    The book takes its title from the first of nine Northern Cheyenne folk tales, illustrated by Indian children in grades 2-8. The stories are: "The Turtle Went to War" about a turtle who makes war on the Indians and takes two scalps; "The Cat", explaining why cats eat first and wash later; "The Frog and the Watersnake",…

  1. Fréquence et facteurs de risque maternels de la mort fœtale in utero à Kamina, République Démocratique du Congo

    PubMed Central

    Kangulu, Ignace Bwana; A'Nkoy, Albert Mwembo Tambwe; Lumbule, John Ngoy; Umba, Elie Kilolo Ngoy; Nzaji, Michel Kabamba; Kayamba, Prosper Kalenga Muenze

    2016-01-01

    Introduction La mort fœtale in utero constitue un problème fréquent dans la pratique obstétricale. Les objectifs de cette étude étaient de déterminer la fréquence et d'identifier les facteurs de risque de la mort fœtale in utero à l'Hôpital Général de Référence de Kamina. Méthodes L’étude était effectuée en deux temps. En premier lieu, une étude descriptive transversale sur 379 accouchements qui avait permis de déterminer la fréquence de la mort fœtale in utero. La détermination des facteurs de risque était faite à l'aide d'une étude cas-témoins dans laquelle les caractéristiques de 53 morts in utero ont été comparées à 106 témoins constitués des naissances vivantes et à terme. Résultats La fréquence de la mort fœtale in utero à l'Hôpital Général de Référence de Kamina était de 13,9%. Après ajustement, l’âge maternel de plus de 35 ans (OR = 6,23; IC= (1,30-29,80)), l'antécédent de mort fœtale in utero (OR = 3,13; IC= (1,06-9,27)) et la maladie au cours de la grossesse (OR = 31,6, IC= (7,66-130,71)) ont été retenus comme facteurs significativement associés à l'augmentation de la survenue de la mort fœtale. L'instruction élevée de la mère (OR = 0,11; IC= IC= [0,03-0,42]) et la résidence à Kamina (OR = 0,23; IC= (0,08-0,62)) diminuaient ce risque. Conclusion La fréquence de la mort fœtale in utero était de 13,9%. L’âge maternel avancé l'antécédent de mort in utero et la maladie au cours de la grossesse étaient associés à la mort fœtale in utero mais par contre, l'instruction élevée de la femme et la résidence à Kamina diminuaient le risque. La surveillance des gestantes à risque, le dépistage et la prise en charge des maladies pendant la grossesse s'avèrent nécessaires dans la perspective de réduire la fréquence de la mort fœtale in utero dans notre milieu. PMID:27279941

  2. Efficient gene targeting by homology-directed repair in rat zygotes using TALE nucleases.

    PubMed

    Remy, Séverine; Tesson, Laurent; Menoret, Séverine; Usal, Claire; De Cian, Anne; Thepenier, Virginie; Thinard, Reynald; Baron, Daniel; Charpentier, Marine; Renaud, Jean-Baptiste; Buelow, Roland; Cost, Gregory J; Giovannangeli, Carine; Fraichard, Alexandre; Concordet, Jean-Paul; Anegon, Ignacio

    2014-08-01

    The generation of genetically modified animals is important for both research and commercial purposes. The rat is an important model organism that until recently lacked efficient genetic engineering tools. Sequence-specific nucleases, such as ZFNs, TALE nucleases, and CRISPR/Cas9 have allowed the creation of rat knockout models. Genetic engineering by homology-directed repair (HDR) is utilized to create animals expressing transgenes in a controlled way and to introduce precise genetic modifications. We applied TALE nucleases and donor DNA microinjection into zygotes to generate HDR-modified rats with large new sequences introduced into three different loci with high efficiency (0.62%-5.13% of microinjected zygotes). Two of these loci (Rosa26 and Hprt1) are known to allow robust and reproducible transgene expression and were targeted for integration of a GFP expression cassette driven by the CAG promoter. GFP-expressing embryos and four Rosa26 GFP rat lines analyzed showed strong and widespread GFP expression in most cells of all analyzed tissues. The third targeted locus was Ighm, where we performed successful exon exchange of rat exon 2 for the human one. At all three loci we observed HDR only when using linear and not circular donor DNA. Mild hypothermic (30°C) culture of zygotes after microinjection increased HDR efficiency for some loci. Our study demonstrates that TALE nuclease and donor DNA microinjection into rat zygotes results in efficient and reproducible targeted donor integration by HDR. This allowed creation of genetically modified rats in a work-, cost-, and time-effective manner. © 2014 Remy et al.; Published by Cold Spring Harbor Laboratory Press.

  3. Erythroid activator NF-E2, TAL1 and KLF1 play roles in forming the LCR HSs in the human adult β-globin locus.

    PubMed

    Kim, Yea Woon; Yun, Won Ju; Kim, AeRi

    2016-06-01

    The β-like globin genes are developmental stage specifically transcribed in erythroid cells. The transcription of the β-like globin genes requires erythroid specific activators such as GATA-1, NF-E2, TAL1 and KLF1. However, the roles of these activators have not fully elucidated in transcription of the human adult β-globin gene. Here we employed hybrid MEL cells (MEL/ch11) where a human chromosome containing the β-globin locus is present and the adult β-globin gene is highly transcribed by induction. The roles of erythroid specific activators were analyzed by inhibiting the expression of NF-E2, TAL1 or KLF1 in MEL/ch11 cells. The loss of each activator decreased the transcription of human β-globin gene, locus wide histone hyperacetylation and the binding of other erythroid specific activators including GATA-1, even though not affecting the expression of other activators. Notably, sensitivity to DNase I was reduced in the locus control region (LCR) hypersensitive sites (HSs) with the depletion of activators. These results indicate that NF-E2, TAL1 and KLF1, all activators play a primary role in HSs formation in the LCR. It might contribute to the transcription of human adult β-globin gene by allowing the access of activators and cofactors. The roles of activators in the adult β-globin locus appear to be different from the roles in the early fetal locus. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. The Emergence of Fairy Tale Literacy: A Multiple Case Study on Promoting Critical Literacy of Children through a Juxtaposed Reading of Classic Fairy Tales and Their Contemporary Disruptive Variants

    ERIC Educational Resources Information Center

    Li, Chieh-Lan

    2010-01-01

    Children nowadays perceive fairy tales from a number of sources; however, the strongest prior impressions toward this genre held by most youngsters are still built on the popular mass media-based adaptations such as the animated films or books of fairytale retellings by the Walt Disney Company. In order to make a change to such an undesirable…

  5. Intercultural Manifestations of Racial, Language, and Class Privilege in Schooling: An Autoethnographic Tale

    ERIC Educational Resources Information Center

    Marx, Sherry

    2017-01-01

    In this autoethnographic tale, I tell the story of my own family's experience with race, class, and language privilege. In particular, I focus on my children's experience with elementary schooling in the United States and Hungary. Their intercultural education experience vividly illuminates the socially and culturally constructed nature of race,…

  6. From Black Power to Hip-Hop: Jeffrey O.G. Ogbar

    ERIC Educational Resources Information Center

    Smiles, Robin V.

    2005-01-01

    While history for most conjures up images of places and experiences far removed, for Dr. Jeffrey O.G. Ogbar, the field provides a "wonderful medium" to illuminate contemporary issues as well. Much of Ogbar's current research centers on events occurring in the latter half of the 20th century, such as the civil rights and Black power…

  7. Once upon Anion: A Tale of Photodetachment

    NASA Astrophysics Data System (ADS)

    Lineberger, W. Carl

    2013-04-01

    This contribution is very much a personal history of a journey through the wonderful world of anion chemistry, and a tale of how advances in laser technologies, theoretical methods, and computational capabilities continuously enabled advances in our understanding. It is a story of the excitement and joy that come from the opportunity to add to the fabric of science, and to do so by working as a group of excited explorers with common goals. The participants in this journey include me, my students and postdoctoral associates, my collaborators, and our many generous colleagues. It all happened, in the words of the Beatles, “with a little help from my friends.” Actually, it was so much more than a little help!

  8. Coleman works at the AR OGS Rack in the Node 3

    NASA Image and Video Library

    2011-02-08

    ISS026-E-025143 (8 Feb. 2011) --- NASA astronaut Catherine (Cady) Coleman, Expedition 26 flight engineer, works at the Atmosphere Revitalization / Oxygen Generation System (AR OGS) rack in the Harmony node of the International Space Station. Coleman collected recirculation loop samples for subsequent analysis for pH value.

  9. Coleman works at the AR OGS Rack in the Node 3

    NASA Image and Video Library

    2011-02-08

    ISS026-E-025142 (8 Feb. 2011) --- NASA astronaut Catherine (Cady) Coleman, Expedition 26 flight engineer, works at the Atmosphere Revitalization / Oxygen Generation System (AR OGS) rack in the Harmony node of the International Space Station. Coleman collected recirculation loop samples for subsequent analysis for pH value.

  10. Dede Korkut Tales Can Inspire the Turkish ESL Students to Speak Better English

    ERIC Educational Resources Information Center

    Yurtbasi, Metin

    2016-01-01

    Bayburt University's English Language Teaching (ELT) department, is starting its courses as of 2016 fall season, using the Turkish sage Dede Korkut's tales as part of its speech training curriculum. The story "Wild Dumrul" presented in this article is famous in world literature for its theme of "marital love and sacrifice."…

  11. Folk Tales: Getting to Know Southeast Asia. Southeast Asia Curriculum Series, No. 1.

    ERIC Educational Resources Information Center

    Ridgley, Marlene

    A teaching/learning plan designed to provide the elementary classroom teacher with an overview of the geography, environment, culture, and people of Southeast Asia includes five sections on the following subjects: geography, animals, plants, social roles and occupations, and religion. Through the use of folk tales from each of six Southeast Asian…

  12. Tuberculose pariétale compliquée d’embolie pulmonaire

    PubMed Central

    Bopaka, Regis Gothard; Bemba, Presley Lee Esthel; Janah, Hind; Okombi, Franck Hardain Okemba; Jabri, Hasna; Khattabi, Wiam El; Afif, Hicham

    2017-01-01

    La tuberculose est une maladie infectieuse qui reste fréquente dans les pays en développement. La localisation peut être pulmonaire ou extra-pulmonaire. Cette forme extra-pulmonaire pose un grand problème diagnostique. Nous rapportons le cas d'un patient présentant une embolie pulmonaire révélant une tuberculose pariétale. A travers cette observation, nous soulignons la nécessité de rechercher l'étiologie devant une embolie pulmonaire. PMID:28819528

  13. Sedimentary Facies and their possible significance in Holocene paleoclimate reconstruction: Example of Baraila Tal, Central Ganga Plains

    NASA Astrophysics Data System (ADS)

    Misra, Pavani; Sinha, Rajiv; Tandon, Sampat Kumar

    2016-04-01

    To seek insights into natural climate variability on decadal/ centennial or half-millennial scale, we need to examine Holocene stratigraphic records. Due to the paucity of high-resolution Holocene continental records in India, Holocene climate change has mostly been studied from the marine sediments. Since agricultural communities are sustained by the resources of large river basins, it is important to understand the response of these systems directly to any climate change. The fluvial archive itself offers a relatively low resolution record, but the ox-bows and meander cut-offs in these basins act as semi-closed systems and hence offer the possibility of obtaining better time resolved stratigraphic data. Therefore, lakes from Central Ganga Plains can be regarded as good terrestrial archives; these have been inadequately investigated as compared to the lakes in western India which have been studied with multi-proxy approaches and show major abrupt climatic disruptions. Previous work on some of the lakes in the Central Ganga Plains is largely based on fossil pollen and commonly shows an alternating increase in tree pollen and grassland pollen representing a shifting trend of warm and humid conditions (from 12,500 to 6,400 and 4,800 to 2000 cal yrs BP), to cold and dry spells, respectively. Lake organic facies from Sanai Tal follow an increasing trend of δ13C values from 15,000 to 5,800 14C yr BP, which indicate an enhanced aquatic productivity during that period, except between 11,500 to 10,500 14C yr BP when lighter δ13C values are observed (Sharma et al., 2004), indicating a dry climate for this short period. Against the above background of previous studies, the Baraila Tal, a lake in the Central Ganga Plains has been chosen to obtain a relatively better time-resolved stratigraphy and to characterize its lithofacies for assessing proxy-paleoclimatic data. We have carried out sedimentary facies analysis for three trenches in the Baraila Tal; the major sand, silt

  14. Crafting the TALE: construction of a measure to assess the functions of autobiographical remembering.

    PubMed

    Bluck, Susan; Alea, Nicole

    2011-07-01

    Theory suggests that autobiographical remembering serves several functions. This research builds on previous empirical efforts (Bluck, Alea, Habermas, & Rubin, 2005) with the aim of constructing a brief, valid measure of three functions of autobiographical memory. Participants (N=306) completed 28 theoretically derived items concerning the frequency with which they use autobiographical memory to serve a variety of functions. To examine convergent and discriminant validity, participants rated their tendency to think about and talk about the past, and measures of future time orientation, self-concept clarity, and trait personality. Confirmatory factor analysis of the function items resulted in a respecified model with 15 items in three factors. The newly developed Thinking about Life Experiences scale (TALE) shows good internal consistency as well as convergent validity for three subscales: Self-Continuity, Social-Bonding, and Directing-Behaviour. Analyses demonstrate factorial equivalence across age and gender groups. Potential use and limitations of the TALE are discussed.

  15. Designed Transcriptional Regulation in Mammalian Cells Based on TALE- and CRISPR/dCas9.

    PubMed

    Lebar, Tina; Jerala, Roman

    2018-01-01

    Transcriptional regulation lies at the center of many cellular processes and is the result of cellular response to different external and internal signals. Control of transcription of selected genes enables an unprecedented access to shape the cellular response. While orthogonal transcription factors from bacteria, yeast, plants, or other cells have been used to introduce new cellular logic into mammalian cells, the discovery of designable modular DNA binding domains, such as Transcription Activator-Like Effectors (TALEs) and the CRISPR system, enable targeting of almost any selected DNA sequence. Fusion or conditional association of DNA targeting domain with transcriptional effector domains enables controlled regulation of almost any endogenous or ectopic gene. Moreover, the designed regulators can be linked into genetic circuits to implement complex responses, such as different types of Boolean functions and switches. In this chapter, we describe the protocols for achieving efficient transcriptional regulation with TALE- and CRISPR-based designed transcription factors in mammalian cells.

  16. A tale of TALE, PREP1, PBX1, and MEIS1: Interconnections and competition in cancer.

    PubMed

    Blasi, Francesco; Bruckmann, Chiara; Penkov, Dmitry; Dardaei, Leila

    2017-05-01

    We report the latest structural information on PREP1 tumor suppressor, the specific "oncogene" and "tumor suppressive" signatures of MEIS1 and PREP1, the molecular rules regulating PREP1 and MEIS1 binding to DNA, and how these can change depending on the interaction with PBX1, cell-type, neoplastic transformation, and intracellular concentration. As both PREP1 and MEIS1 interact with PBX1 they functionally compete with each other. PREP1, PBX1, and MEIS1 TALE-class homeodomain transcription factors act in an interdependent and integrated way in experimental tumorigenesis. We also pool together the plethora of data available in human cancer databanks and connect them with the available molecular information. The emerging picture suggests that a similarly basic approach might be used to better dissect and define other oncogenes and suppressors and better understand human cancer. © 2017 The Authors. BioEssays Published by WILEY Periodicals, Inc.

  17. Engineering synthetic TALE and CRISPR/Cas9 transcription factors for regulating gene expression.

    PubMed

    Kabadi, Ami M; Gersbach, Charles A

    2014-09-01

    Engineered DNA-binding proteins that can be targeted to specific sites in the genome to manipulate gene expression have enabled many advances in biomedical research. This includes generating tools to study fundamental aspects of gene regulation and the development of a new class of gene therapies that alter the expression of endogenous genes. Designed transcription factors have entered clinical trials for the treatment of human diseases and others are in preclinical development. High-throughput and user-friendly platforms for designing synthetic DNA-binding proteins present innovative methods for deciphering cell biology and designing custom synthetic gene circuits. We review two platforms for designing synthetic transcription factors for manipulating gene expression: Transcription activator-like effectors (TALEs) and the RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. We present an overview of each technology and a guide for designing and assembling custom TALE- and CRISPR/Cas9-based transcription factors. We also discuss characteristics of each platform that are best suited for different applications. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Telling tales.

    PubMed

    Denning, Stephen

    2004-05-01

    A carefully chosen story can help the leader of an organization translate an abstract concept into a meaningful mandate for employees. The key is to know which narrative strategies are right for what circumstances. Knowledge management expert Stephen Denning explains that, for optimal effect, form should follow function. Challenging one professional storyteller's view that more is better, Denning points out that it's not always desirable (or practical) to launch into an epic that's jam-packed with complex characters, cleverly placed plot points, an intricate rising action, and a neatly resolved denouement. True, if listeners have time and interest, a narrative-savvy leader can use a vividly rendered tale to promote communication between management and staff, for instance, or even to foster collaboration--especially when the story is emotionally moving. However, if the aim is to motivate people to act when they might not be inclined to do so, it's best to take an approach that's light on detail. Otherwise, the particulars can bog listeners down and prevent them from focusing on the message. Drawing on his experiences at the World Bank and observations made elsewhere, the author provides several dos and don'ts for organizational storytellers, along with examples of narratives that get results. The sidebar "A Storytelling Catalog" presents seven distinct types of stories, the situations in which they should be told, and tips on how to tell them. Many of these aren't even stories in the "well-told" sense--they run the rhetorical gamut from one-liners to full-blown speeches--but they succeed because they're tailored to fit the situation. So even though it's common in business to favor the analytical over the anecdotal, leaders with the strength to push past some initial skepticism about the enterprise of storytelling will find that the creative effort pays off.

  19. SalB inactivation modulates culture supernatant exoproteins and affects autolysis and viability in Enterococcus faecalis OG1RF.

    PubMed

    Shankar, Jayendra; Walker, Rachel G; Wilkinson, Mark C; Ward, Deborah; Horsburgh, Malcolm J

    2012-07-01

    The culture supernatant fraction of an Enterococcus faecalis gelE mutant of strain OG1RF contained elevated levels of the secreted antigen SalB. Using differential fluorescence gel electrophoresis (DIGE) the salB mutant was shown to possess a unique complement of exoproteins. Differentially abundant exoproteins were identified using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Stress-related proteins including DnaK, Dps family protein, SOD, and NADH peroxidase were present in greater quantity in the OG1RF salB mutant culture supernatant. Moreover, several proteins involved in cell wall synthesis and cell division, including d-Ala-d-Lac ligase and EzrA, were present in reduced quantity in OG1RF salB relative to the parent strain. The salB mutant displayed reduced viability and anomalous cell division, and these phenotypes were exacerbated in a gelE salB double mutant. An epistatic relationship between gelE and salB was not identified with respect to increased autolysis and cell morphological changes observed in the salB mutant. SalB was purified as a six-histidine-tagged protein to investigate peptidoglycan hydrolytic activity; however, activity was not evident. High-pressure liquid chromatography (HPLC) analysis of reduced muropeptides from peptidoglycan digested with mutanolysin revealed that the salB mutant and OG1RF were indistinguishable.

  20. Making and Using Astronomical Fairy-tales on DVD in Planetarium

    NASA Astrophysics Data System (ADS)

    Goncharova, V. G.

    2006-08-01

    Teaching and learning of astronomy meets many contradictions: the information should be true, the presentation should be at a professional level yet easy for the teacher, the topic should be related to the everyday life of the students, and have a cultural/historical background; also, it should be understandable for a wide range of ages. We try to meet all these principles making and using a DVD-video "The FairyTale of the Milky Way" which has been presented for several months in the Planetarium of SaintPetersburg, Russia. We present some parts of the tale on screen with comments on the realization of the principles. Astronomy has many places and moments where and when an astronomical idea and discovery shines perfectly for teaching. We selected Prague, the house of Kepler, Christmas evening of the year 1610, the Keplers last Christmas in Prague. He really may have celebrated Christmas with his family just before the smallpox epidemic, which will take the lives of three of them the next year. The Keplers' friend Rudolf II was still the Emperor (for his last year). Kepler really may have shown his children the pages of the just-published Bayer's Atlas of the Constellations. He must have been excited by the discoveries on the southern sky as well as the recent telescopic discoveries by Galileo. He really may have looked at the satellites of Jupiter, the phases of Venus (that was the right month!), the stars and nebula of the Milky Way, the sunspots and lunar craters through one of the telescopes widely distributed in 1610. He wrote 2 books: one about stars (the famous planetary laws!), the other about snowflakes. That was the key moment of his life. Many details making the atmosphere of the moment are in our tale. The real pictures of the epoch are used. In the fairytale, the beautiful telescopic nebula on modern photos appear real: "Helix," "Crab," "Ant," "Cat's Eye," "Butterfly," "Witch," and so on. A simple technique and software to make it is presented. The

  1. A Tale of Two More Metaphors: Storylines about Mathematics Education in Canadian National Media

    ERIC Educational Resources Information Center

    Chorney, Sean; Ng, Oi-Lam; Pimm, David

    2016-01-01

    In this companion piece to the article "A Tale of Two Metaphors: Storylines About Mathematics Education in Canadian National Media" (this issue), we further explore constructed meanings through the use of positioning theory. In our examination of 71 articles in the two Canadian national newspapers ("The Globe and Mail" and…

  2. A tale of two cedars – International symposium on western redcedar and yellow-cedar

    Treesearch

    Constance Harrington

    2010-01-01

    From May 24-28, 2010, an international symposium on western redcedar (Thuja plicata) and yellowcedar (Callitropsis nootkatensis [syn., Chamaecyparis nootkatensis]) was held at the University of Victoria on Vancouver Island in British Columbia, Canada. The symposium was entitled “A Tale of Two Cedars” and...

  3. Reactive transport modeling in the subsurface environment with OGS-IPhreeqc

    NASA Astrophysics Data System (ADS)

    He, Wenkui; Beyer, Christof; Fleckenstein, Jan; Jang, Eunseon; Kalbacher, Thomas; Naumov, Dimitri; Shao, Haibing; Wang, Wenqing; Kolditz, Olaf

    2015-04-01

    Worldwide, sustainable water resource management becomes an increasingly challenging task due to the growth of population and extensive applications of fertilizer in agriculture. Moreover, climate change causes further stresses to both water quantity and quality. Reactive transport modeling in the coupled soil-aquifer system is a viable approach to assess the impacts of different land use and groundwater exploitation scenarios on the water resources. However, the application of this approach is usually limited in spatial scale and to simplified geochemical systems due to the huge computational expense involved. Such computational expense is not only caused by solving the high non-linearity of the initial boundary value problems of water flow in the unsaturated zone numerically with rather fine spatial and temporal discretization for the correct mass balance and numerical stability, but also by the intensive computational task of quantifying geochemical reactions. In the present study, a flexible and efficient tool for large scale reactive transport modeling in variably saturated porous media and its applications are presented. The open source scientific software OpenGeoSys (OGS) is coupled with the IPhreeqc module of the geochemical solver PHREEQC. The new coupling approach makes full use of advantages from both codes: OGS provides a flexible choice of different numerical approaches for simulation of water flow in the vadose zone such as the pressure-based or mixed forms of Richards equation; whereas the IPhreeqc module leads to a simplification of data storage and its communication with OGS, which greatly facilitates the coupling and code updating. Moreover, a parallelization scheme with MPI (Message Passing Interface) is applied, in which the computational task of water flow and mass transport is partitioned through domain decomposition, whereas the efficient parallelization of geochemical reactions is achieved by smart allocation of computational workload over

  4. A TALE of transposition: Tn3-like transposons play a major role in the spread of pathogenicity determinants of Xanthomonas citri and other xanthomonads.

    PubMed

    Ferreira, Rafael Marini; de Oliveira, Amanda Carolina P; Moreira, Leandro M; Belasque, José; Gourbeyre, Edith; Siguier, Patricia; Ferro, Maria Inês T; Ferro, Jesus A; Chandler, Michael; Varani, Alessandro M

    2015-02-17

    Members of the genus Xanthomonas are among the most important phytopathogens. A key feature of Xanthomonas pathogenesis is the translocation of type III secretion system (T3SS) effector proteins (T3SEs) into the plant target cells via a T3SS. Several T3SEs and a murein lytic transglycosylase gene (mlt, required for citrus canker symptoms) are found associated with three transposition-related genes in Xanthomonas citri plasmid pXAC64. These are flanked by short inverted repeats (IRs). The region was identified as a transposon, TnXax1, with typical Tn3 family features, including a transposase and two recombination genes. Two 14-bp palindromic sequences within a 193-bp potential resolution site occur between the recombination genes. Additional derivatives carrying different T3SEs and other passenger genes occur in different Xanthomonas species. The T3SEs include transcription activator-like effectors (TALEs). Certain TALEs are flanked by the same IRs as found in TnXax1 to form mobile insertion cassettes (MICs), suggesting that they may be transmitted horizontally. A significant number of MICs carrying other passenger genes (including a number of TALE genes) were also identified, flanked by the same TnXax1 IRs and delimited by 5-bp target site duplications. We conclude that a large fraction of T3SEs, including individual TALEs and potential pathogenicity determinants, have spread by transposition and that TnXax1, which exhibits all of the essential characteristics of a functional transposon, may be involved in driving MIC transposition. We also propose that TALE genes may diversify by fork slippage during the replicative Tn3 family transposition. These mechanisms may play a crucial role in the emergence of Xanthomonas pathogenicity. Xanthomonas genomes carry many insertion sequences (IS) and transposons, which play an important role in their evolution and architecture. This study reveals a key relationship between transposons and pathogenicity determinants in

  5. A Pedagogical Tale from the Piano Studio: Autoethnography in Early Childhood Music Education Research

    ERIC Educational Resources Information Center

    Gouzouasis, Peter; Ryu, Jee Yeon

    2015-01-01

    Our inquiry centres on a hopeful tale about creative teaching and learning, trusting one's teaching intuition and processes, caring for children, and believing that children will respond to opportunities to learn music when they are invited with thoughtful care. Though the process of writing, both our young student and ourselves, we evoke the…

  6. Comparing top-down and bottom-up estimates of methane emissions across multiple U.S. oil and gas basins provides insights into national O&G emissions, mitigation strategies, and research priorities

    NASA Astrophysics Data System (ADS)

    Lyon, D. R.; Alvarez, R.; Zavala Araiza, D.; Hamburg, S.

    2017-12-01

    We develop a county-level inventory of U.S. anthropogenic methane emissions by integrating multiple data sources including the Drillinginfo oil and gas (O&G) production database, Environmental Protection Agency (EPA) Greenhouse Gas Reporting Program, a previously published gridded EPA Greenhouse Gas Inventory (Maasakkers et al 2016), and recent measurements studies of O&G pneumatic devices, equipment leaks, abandoned wells, and midstream facilities. Our bottom-up estimates of total and O&G methane emissions are consistently lower than top-down, aerial mass balance estimates in ten O&G production areas. We evaluate several hypotheses for the top-down/bottom-up discrepancy including potential bias of the aerial mass balance method, temporal mismatch of top-down and bottom-up emission estimates, and source attribution errors. In most basins, the top-down/bottom-up gap cannot be explained fully without additional O&G emissions from sources not included in traditional inventories, such as super-emitters caused by malfunctions or abnormal process conditions. Top-down/bottom-up differences across multiple basins are analyzed to estimate the magnitude of these additional emissions and constrain total methane emissions from the U.S. O&G supply chain. We discuss the implications for mitigating O&G methane emissions and suggest research priorities for increasing the accuracy of future emission inventories.

  7. Human HOX Proteins Use Diverse and Context-Dependent Motifs to Interact with TALE Class Cofactors.

    PubMed

    Dard, Amélie; Reboulet, Jonathan; Jia, Yunlong; Bleicher, Françoise; Duffraisse, Marilyne; Vanaker, Jean-Marc; Forcet, Christelle; Merabet, Samir

    2018-03-13

    HOX proteins achieve numerous functions by interacting with the TALE class PBX and MEIS cofactors. In contrast to this established partnership in development and disease, how HOX proteins could interact with PBX and MEIS remains unclear. Here, we present a systematic analysis of HOX/PBX/MEIS interaction properties, scanning all paralog groups with human and mouse HOX proteins in vitro and in live cells. We demonstrate that a previously characterized HOX protein motif known to be critical for HOX-PBX interactions becomes dispensable in the presence of MEIS in all except the two most anterior paralog groups. We further identify paralog-specific TALE-binding sites that are used in a highly context-dependent manner. One of these binding sites is involved in the proliferative activity of HOXA7 in breast cancer cells. Together these findings reveal an extraordinary level of interaction flexibility between HOX proteins and their major class of developmental cofactors. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Biochemistry of the tale transcription factors PREP, MEIS, and PBX in vertebrates.

    PubMed

    Longobardi, E; Penkov, D; Mateos, D; De Florian, G; Torres, M; Blasi, Francesco

    2014-01-01

    TALE (three amino acids loop extension) homeodomain transcription factors are required in various steps of embryo development, in many adult physiological functions, and are involved in important pathologies. This review focuses on the PREP, MEIS, and PBX sub-families of TALE factors and aims at giving information on their biochemical properties, i.e., structure, interactors, and interaction surfaces. Members of the three sets of protein form dimers in which the common partner is PBX but they can also directly interact with other proteins forming higher-order complexes, in particular HOX. Finally, recent advances in determining the genome-wide DNA-binding sites of PREP1, MEIS1, and PBX1, and their partial correspondence with the binding sites of some HOX proteins, are reviewed. These studies have generated a few general rules that can be applied to all members of the three gene families. PREP and MEIS recognize slightly different consensus sequences: PREP prefers to bind to promoters and to have PBX as a DNA-binding partner; MEIS prefers HOX as partner, and both PREP and MEIS drive PBX to their own binding sites. This outlines the clear individuality of the PREP and MEIS proteins, the former mostly devoted to basic cellular functions, the latter more to developmental functions. Copyright © 2013 Wiley Periodicals, Inc.

  9. "[This] Book of Odd Tales/Which Transform the Brothers Grimm": Teaching Anne Sexton's "Transformations"

    ERIC Educational Resources Information Center

    Keely, Karen A.

    2008-01-01

    Folklorist Andrew Lang, in his Preface to his 1910 edited collection "The Lilac Fairy Book", celebrates the ongoing repetition and retelling of fairy tales, including both the cozy retelling by the family fireplace. In the century since Lang wrote these words, many authors have joined the ranks of Shakespeare and Homer in putting fairy tale…

  10. Ego Boundary Deficits and the Negative Therapeutic Inter-Action: A Tale of a Whale, a Whale of a Tale.

    PubMed

    Peterson, Charles A

    2017-06-01

    Defined variously and unsatisfactorily as a worsening of the patient's condition following a correct interpretation, the negative therapeutic reaction is typically blamed on the patient: "the operation was a success but the patient died." For most neurotic patients unconscious guilt objects to progress and activates the need to suffer. For most character-disturbed patients envy cannot bear the analyst's cleverness. However, patients with ego boundary problems-even sectors of psychosis-may require a different explanatory mechanism, where a correct interpretation may be experienced as a penetration and an engulfment, threatening the intactness of the self. A short-term, time-limited, psychoanalytic psychotherapy that went off the rails following a correct but ill-timed interpretation is presented as an opportunity to amend analytic theory, here favoring the interactional over the intrapsychic. Herman Melville helps tell the tale.

  11. Manipulation of the Family Photo Album: Esther Parada's Transplant--A Tale of Three Continents

    ERIC Educational Resources Information Center

    Eggemeyer, Valerie

    2004-01-01

    In this article, the author focuses on Esther Parada's non-traditional use of the Web to communicate her art, and offers a critique of Parada's work, "Transplant: A Tale of Three Continents," and suggestions for critiquing Web art in the school classroom. Parada creates an intersection between this new medium and the more traditional medium of…

  12. Reactive transport modeling in variably saturated porous media with OGS-IPhreeqc

    NASA Astrophysics Data System (ADS)

    He, W.; Beyer, C.; Fleckenstein, J. H.; Jang, E.; Kalbacher, T.; Shao, H.; Wang, W.; Kolditz, O.

    2014-12-01

    Worldwide, sustainable water resource management becomes an increasingly challenging task due to the growth of population and extensive applications of fertilizer in agriculture. Moreover, climate change causes further stresses to both water quantity and quality. Reactive transport modeling in the coupled soil-aquifer system is a viable approach to assess the impacts of different land use and groundwater exploitation scenarios on the water resources. However, the application of this approach is usually limited in spatial scale and to simplified geochemical systems due to the huge computational expense involved. Such computational expense is not only caused by solving the high non-linearity of the initial boundary value problems of water flow in the unsaturated zone numerically with rather fine spatial and temporal discretization for the correct mass balance and numerical stability, but also by the intensive computational task of quantifying geochemical reactions. In the present study, a flexible and efficient tool for large scale reactive transport modeling in variably saturated porous media and its applications are presented. The open source scientific software OpenGeoSys (OGS) is coupled with the IPhreeqc module of the geochemical solver PHREEQC. The new coupling approach makes full use of advantages from both codes: OGS provides a flexible choice of different numerical approaches for simulation of water flow in the vadose zone such as the pressure-based or mixed forms of Richards equation; whereas the IPhreeqc module leads to a simplification of data storage and its communication with OGS, which greatly facilitates the coupling and code updating. Moreover, a parallelization scheme with MPI (Message Passing Interface) is applied, in which the computational task of water flow and mass transport is partitioned through domain decomposition, whereas the efficient parallelization of geochemical reactions is achieved by smart allocation of computational workload over

  13. Power Relationships in Rumpelstiltskin: A Textual Comparison of a Traditional and a Reconstructed Fairy Tale

    ERIC Educational Resources Information Center

    Kelley, Jane E.

    2008-01-01

    Reconstructed fairy tales provide a different point of view and challenge the assumptions of a common set of values; for that reason, these stories provide a medium in which to examine power relationships in texts by applying a critical multicultural analysis (Botelho & Rudman, forthcoming, 2008, "A critical multicultural analysis of children's…

  14. The El-Tal El-Kebir story: an example of social accountability from Egypt.

    PubMed

    Talaat, Wagdy; el-Wazir, Yasser

    2012-01-01

    In 1985, the Faculty of Medicine at Suez Canal University responded to a request from the people of El-Tal El-Kebir, a district in Ismailia Governorate, Egypt, to assist them in addressing their poor health statistics. After an initial visit, the team realized that any long-term solution in dealing with and improving their community health problems needed a true inter-sectoral collaborative approach, with the involvement of other sectors such as agriculture, veterinary medicine, and education. The team also realized that establishing a true partnership with the community as well as the local governmental agencies was indispensible in order to maintain any long-term effects. In this article, we will describe how the medical school mobilized other sectors to improve the community health. The methodology adopted during this example of providing community outreach services was concordant with the principles of social accountability, which was later described by the World Health Organization. Our multi-sectoral team has established several projects for enhancing community participation in solving their own health problems. Medical schools can lead a community development project in collaboration with the community.

  15. Exploring U.S. Westward Expansion in the Elementary and Middle School Curriculum through Tall Tales

    ERIC Educational Resources Information Center

    Almerico, Gina M.; Martin, Nicole; Masuck, William; Strickland, Cynthia; Thomas, Jessica

    2012-01-01

    Teaching social studies in the elementary and middle school curriculum is enhanced by incorporating quality children's and adolescent literature and strategies that bring the human element into play. American tall tales are a genre unique to the history of our nation and provide a glimpse into the way early settlers of the west envisioned heroism…

  16. Folktale Themes and Activities for Children. Volume 2: Trickster and Transformation Tales. Learning through Folklore Series.

    ERIC Educational Resources Information Center

    Kraus, Anne Marie

    This companion volume to "Folktale Themes Volume 1: Pourquoi Tales," shows educators how to use folktales to provide meaningful, educational experiences for children. This book provides a complete package using folktales in the classroom--activity pages, teaching ideas, story themes, and an annotated bibliography of further reading for a…

  17. Linguistic and Cognitive Characteristics of the Composition of the Text of J. K. Rowling's English Tales

    ERIC Educational Resources Information Center

    Solodova, Elena

    2015-01-01

    This article focuses on linguistic and cognitive characteristics inherent in the composition of the English postmodern tales written by J.K. Rowling. The composition of the text is viewed as linguistic and cognitive construal that integrates compositional plot structure, compositional meaning structure, linguistic and stylistic means of their…

  18. Comparison of TALE designer transcription factors and the CRISPR/dCas9 in regulation of gene expression by targeting enhancers

    PubMed Central

    Gao, Xuefei; Tsang, Jason C.H.; Gaba, Fortis; Wu, Donghai; Lu, Liming; Liu, Pentao

    2014-01-01

    The transcription activator–like effectors (TALEs) and the RNA-guided clustered regularly interspaced short palindromic repeat (CRISPR) associated protein (Cas9) utlilize distinct molecular mechanisms in targeting site recognition. The two proteins can be modified to carry additional functional domains to regulate expression of genomic loci in mammalian cells. In this study, we have compared the two systems in activation and suppression of the Oct4 and Nanog loci by targeting their enhancers. Although both are able to efficiently activate the luciferase reporters, the CRISPR/dCas9 system is much less potent in activating the endogenous loci and in the application of reprogramming somatic cells to iPS cells. Nevertheless, repression by CRISPR/dCas9 is comparable to or even better than TALE repressors. We demonstrated that dCas9 protein binding results in significant physical interference to binding of native transcription factors at enhancer, less efficient active histone markers induction or recruitment of activating complexes in gene activation. This study thus highlighted the merits and drawbacks of transcription regulation by each system. A combined approach of TALEs and CRISPR/dCas9 should provide an optimized solution to regulate genomic loci and to study genetic elements such as enhancers in biological processes including somatic cell reprogramming and guided differentiation. PMID:25223790

  19. The Integration of Gender into the Teaching of Classical Social Theory: Help from "The Handmaid's Tale."

    ERIC Educational Resources Information Center

    Gotsch-Thomson, Susan

    1990-01-01

    Describes how gender is integrated into a classical social theory course by including a female theorist in the reading assignments and using "The Handmaid's Tale" by Margaret Atwood as the basis for class discussion. Reviews the course objectives and readings; describes the process of the class discussions; and provides student…

  20. Young Adult Fairy Tales for the New Age: Francesca Lia Block's "The Rose and the Beast."

    ERIC Educational Resources Information Center

    Russell, David L.

    2002-01-01

    Considers how Francesca Lia Block's "The Rose and the Beast" attests to the resilience of the traditional folktale form. Describes how Block's work is a modern adaptation of some of the most familiar old tales, all with heroines struggling against plastic, soulless culture beset by drugs, sex, and violence. (SG)

  1. Genome Engineering with TALE and CRISPR Systems in Neuroscience.

    PubMed

    Lee, Han B; Sundberg, Brynn N; Sigafoos, Ashley N; Clark, Karl J

    2016-01-01

    Recent advancement in genome engineering technology is changing the landscape of biological research and providing neuroscientists with an opportunity to develop new methodologies to ask critical research questions. This advancement is highlighted by the increased use of programmable DNA-binding agents (PDBAs) such as transcription activator-like effector (TALE) and RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated (Cas) systems. These PDBAs fused or co-expressed with various effector domains allow precise modification of genomic sequences and gene expression levels. These technologies mirror and extend beyond classic gene targeting methods contributing to the development of novel tools for basic and clinical neuroscience. In this Review, we discuss the recent development in genome engineering and potential applications of this technology in the field of neuroscience.

  2. A New Approach to Dissect Nuclear Organization: TALE-Mediated Genome Visualization (TGV).

    PubMed

    Miyanari, Yusuke

    2016-01-01

    Spatiotemporal organization of chromatin within the nucleus has so far remained elusive. Live visualization of nuclear remodeling could be a promising approach to understand its functional relevance in genome functions and mechanisms regulating genome architecture. Recent technological advances in live imaging of chromosomes begun to explore the biological roles of the movement of the chromatin within the nucleus. Here I describe a new technique, called TALE-mediated genome visualization (TGV), which allows us to visualize endogenous repetitive sequence including centromeric, pericentromeric, and telomeric repeats in living cells.

  3. Fairy Tales and Other Stories as Spiritual Guides for Children of War: An Auto-Ethnographic Perspective

    ERIC Educational Resources Information Center

    Feuerverger, Grace

    2010-01-01

    This article dares to suggest that the use of fairy tales as a pedagogical tool for children in and out of classrooms is and always will be about uplifting the human spirit: a way to survive; a pathway toward hope, especially for vulnerable children suffering from the trauma of war. (Contains 1 note.)

  4. Ausgerechnet "Rumpelstilzchen?" Grimms Marchen im DaF-Unterricht (Really Rumpelstilskin? Grimm's Fairy Tales in German as a Foreign Language Instruction).

    ERIC Educational Resources Information Center

    Weber, Hans

    2000-01-01

    Suggests the use of fairy tales in German foreign language instruction at the intermediate level. This suggestion is established using features of the Grimm genre and clarified using concrete examples. (Author/DMK)

  5. When Little Girls Become Junior Connoisseurs: A Cautionary Tale of Art Museum Education in the Hyperreal

    ERIC Educational Resources Information Center

    Mayer, Melinda M.

    2006-01-01

    Introducing the tale--A young girl about eleven years old appeared on the TV screen. She stood in an art museum expounding upon the painting hanging behind her. She talked about the artist and what the image portrayed. With an air of elitist prissiness that suited the museum environment, the girl delivered her presentation to a group of…

  6. Development of cereal-based functional food using cereal-mix substrate fermented with probiotic strain - Pichia kudriavzevii OG32.

    PubMed

    Ogunremi, Omotade R; Agrawal, Renu; Sanni, Abiodun I

    2015-11-01

    Probiotic strains contribute to the functionality of foods during fermentation. In this present work, cereal-mix was fermented with probiotic Pichia kudriavzevii OG32. Selected fermentation parameters and functional properties of the product were determined. The growth of Pichia kudriavzevii OG32 was supported by the cereal-mix containing 1% salt and 0.2% red chili powder to counts of between 7.46 and 8.22 Log10 cfu/mL within 24 h. Pichia kudriavzevii OG32 increased the viscosity of cereal-mix with the highest inoculum size (1.84x105cfu/ml) giving the highest viscosity of 1793.6 mPa.S. An inoculum size of 1.98 × 10(4) cfu/mL gave the most acceptable product based on the sensory evaluation by the panelist. Forty volatile compounds were identified in the fermented product, while acids (32.21%) and esters (32.37%) accounted for the largest proportions. The cereal-based fermented product scavenged DPPH from 200 μmol/L methanolic solution by 55.71%. Probiotic yeast improved the sensory and some functional properties of cereal-based substrate during fermentation. This is one of the first reports on the volatile composition of cereal-based functional food produced with probiotic yeast.

  7. Genome Engineering with TALE and CRISPR Systems in Neuroscience

    PubMed Central

    Lee, Han B.; Sundberg, Brynn N.; Sigafoos, Ashley N.; Clark, Karl J.

    2016-01-01

    Recent advancement in genome engineering technology is changing the landscape of biological research and providing neuroscientists with an opportunity to develop new methodologies to ask critical research questions. This advancement is highlighted by the increased use of programmable DNA-binding agents (PDBAs) such as transcription activator-like effector (TALE) and RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated (Cas) systems. These PDBAs fused or co-expressed with various effector domains allow precise modification of genomic sequences and gene expression levels. These technologies mirror and extend beyond classic gene targeting methods contributing to the development of novel tools for basic and clinical neuroscience. In this Review, we discuss the recent development in genome engineering and potential applications of this technology in the field of neuroscience. PMID:27092173

  8. "Why Will You Say That I Am Mad?" Using Poe's "Tell-Tale Heart" as a Composition Model.

    ERIC Educational Resources Information Center

    Bates, Laura Raidonis

    1998-01-01

    Describes an exercise for basic writers which encompasses reading, listening, and writing. Finds that Edgar Allan Poe's "Tell-Tale Heart" has an effective vocabulary, a first-person conversational tone for the "mad" voice, and a second-person direct address that makes it easy to follow. Notes that inexperienced readers can…

  9. The Ordinary and the Fabulous: An Introduction to Myths, Legends, and Fairy Tales for Teachers and Storytellers.

    ERIC Educational Resources Information Center

    Cook, Elizabeth

    Written for teachers, librarians, students, parents, and other storytellers, this book emphasizes the value and enchantment which children can find in the fabulous stories of four main European traditions--Greek myths and legends, Northern myths and legends, Arthurian Romances, and fairy tales. The four chapters contain (1) discussions of myths,…

  10. Interventions et techniques de diagnostic prénatal visant l'obtention d'un prélèvement fœtal à des fins diagnostiques : Risques et avantages pour la mère et le fœtus.

    PubMed

    Wilson, R Douglas; Gagnon, Alain; Audibert, François; Campagnolo, Carla; Carroll, June

    2016-12-01

    Offrir aux fournisseurs de soins de maternité et à leurs patientes des lignes directrices factuelles contemporaines en ce qui concerne les services de counseling traitant des risques et des avantages maternels propres à la tenue des interventions diagnostiques prénatales orientées par échographie (et/ou des techniques permettant l'établissement d'un diagnostic génétique) nécessaires dans les cas où il a été établi pendant la période prénatale que la grossesse serait exposée à des risques, ainsi qu'en ce qui concerne la prise de décisions subséquentes quant à la prise en charge de la grossesse (questions abordant des aspects tels que le niveau du fournisseur de soins obstétricaux, la surveillance prénatale, le lieu où devraient se dérouler les soins et l'accouchement, et la décision de poursuivre ou d'interrompre la grossesse). La présente directive clinique se limite aux services de counseling traitant des risques et des avantages maternels, et aux décisions en matière de prise en charge de la grossesse pour les femmes qui nécessitent (ou qui envisagent) la mise en œuvre d'une intervention ou d'une technique effractive orientée par échographie aux fins de l'établissement d'un diagnostic prénatal. Femmes enceintes identifiées, à la suite de la mise en œuvre de protocoles établis de dépistage prénatal (taux sériques maternels ± imagerie, résultats d'analyse de l'ADN acellulaire indiquant des risques élevés, résultats anormaux au moment de l'imagerie fœtale diagnostique ou antécédents familiaux de troubles héréditaires), comme étant exposées à un risque accru d'anomalie génétique fœtale. Ces femmes pourraient nécessiter ou demander des services de counseling au sujet des risques et des avantages pour la grossesse de la tenue d'une intervention effractive orientée par échographie visant à déterminer l'étiologie, le diagnostic, et/ou la pathologie de possibles anomalies fœtales. RéSULTATS: La litt

  11. Tales of the Earth - Paroxysms and Perturbations of the Blue Planet

    NASA Astrophysics Data System (ADS)

    Officer, Charles; Page, Jake

    1994-05-01

    In Maryland, late in the Spring of 1816, the snow fell brown, and blue, and even red. Brown snow fell in Hungary that year, and in the village of Taranto in southern Italy, where any snow is rare, the red and yellow snow caused great alarm. In New England, 1816 was called the Year Without a Summer. Crops failed throughout America, the price of corn and wheat soared, and farmers (lacking feed) sold off livestock, bringing about a collapse in beef and pork prices. In western Europe it was even worse, with food riots and armed mobs raiding bakeries and grain markets. This turmoil followed a catastrophic volcanic eruption a year earlier on the other side of the world--the April 1815 explosion of the volcano Tambora, on the Indonesian island of Sumbawa--a blast heard almost a thousand miles away in Sumatra. In Tales of the Earth , Charles Officer and Jake Page describe--often through eye-witness accounts and through the commentary of prominent figures--some of the great events of environmental history. From natural catastrophes such as the Tambora eruption, the great Lisbon earthquake of 1755, and the ice ages, to manmade disasters such as the nuclear fallout from Chernobyl, the killer smog of 1952 in London which killed some four thousand people, acid rain, and the progressive depletion of the ozone layer, Officer and Page provide phenomenal accounts of the earthshattering events that have changed the course of history. A fascinating discussion of natures power over humanity, as well as the trouble humanity makes for nature, Tales of the Earth will interest anyone concerned with the environmental and the natural world.

  12. Functional expression of SCL/TAL1 interrupting locus (Stil) protects retinal dopaminergic cells from neurotoxin-induced degeneration.

    PubMed

    Li, Jingling; Li, Ping; Carr, Aprell; Wang, Xiaokai; DeLaPaz, April; Sun, Lei; Lee, Eric; Tomei, Erika; Li, Lei

    2013-01-11

    We previously isolated a dominant mutation, night blindness b (nbb), which causes a late onset of retinal dopaminergic cell degeneration in zebrafish. In this study, we cloned the zebrafish nbb locus. Sequencing results revealed that nbb is a homolog of the vertebrate SCL/TAL1 interrupting locus (Stil). The Stil gene has been shown to play important roles in the regulation of vertebrate embryonic neural development and human cancer cell proliferation. In this study, we demonstrate that functional expression of Stil is also required for neural survival. In zebrafish, decreased expression of Stil resulted in increased toxic susceptibility of retinal dopaminergic cells to 6-hydroxydopamine. Increases in Stil-mediated Shh signaling transduction (i.e. by knocking down the Shh repressor Sufu) prevented dopaminergic cell death induced by neurotoxic insult. The data suggest that the oncogene Stil also plays important roles in neural protection.

  13. Reflexivity in the Interstices: A Tale of Reflexivity at Work in, during, and behind the Scenes

    ERIC Educational Resources Information Center

    Wickens, Corrine M.; Cohen, James A.; Walther, Carol S.

    2017-01-01

    This article is a story of how the authors came to make sense of the significance of those words in relation to gender, race/ethnicity, and citizenship in writing a manuscript about L[subscript 1]L[subscript 2] acquisition. It is a tale about how Reflexivity wove itself into the conversations, into the writing, into the in-between spaces, the…

  14. Site- and strand-specific nicking of DNA by fusion proteins derived from MutH and I-SceI or TALE repeats.

    PubMed

    Gabsalilow, Lilia; Schierling, Benno; Friedhoff, Peter; Pingoud, Alfred; Wende, Wolfgang

    2013-04-01

    Targeted genome engineering requires nucleases that introduce a highly specific double-strand break in the genome that is either processed by homology-directed repair in the presence of a homologous repair template or by non-homologous end-joining (NHEJ) that usually results in insertions or deletions. The error-prone NHEJ can be efficiently suppressed by 'nickases' that produce a single-strand break rather than a double-strand break. Highly specific nickases have been produced by engineering of homing endonucleases and more recently by modifying zinc finger nucleases (ZFNs) composed of a zinc finger array and the catalytic domain of the restriction endonuclease FokI. These ZF-nickases work as heterodimers in which one subunit has a catalytically inactive FokI domain. We present two different approaches to engineer highly specific nickases; both rely on the sequence-specific nicking activity of the DNA mismatch repair endonuclease MutH which we fused to a DNA-binding module, either a catalytically inactive variant of the homing endonuclease I-SceI or the DNA-binding domain of the TALE protein AvrBs4. The fusion proteins nick strand specifically a bipartite recognition sequence consisting of the MutH and the I-SceI or TALE recognition sequences, respectively, with a more than 1000-fold preference over a stand-alone MutH site. TALE-MutH is a programmable nickase.

  15. Duss Fairy Tales: some data from a new evaluation form.

    PubMed

    Mazzeschi, C; Lis, A; Calvo, V; Vallone, V; Superchi, E

    2001-12-01

    The purpose of this paper is to extend the research on the Duss Fairy Tales in an Italian sample. Attention has been paid, in particular, to the study of some variables identified in a newly devised schedule. The protocols were scored for four indexes: (1) the main hero of the stories, (2) number and types of characters, (3) number of emotions expressed, and (4) number of heroes' and characters' actions and behaviors. Subjects were 70 children aged 3.5 to 10.5 yr. enrolled in kindergartens and elementary schools in Italy. The relationships of scores with age and sex were also investigated. There was an increase across three age groups in the richness of stories in terms of emotions and characters' identification.

  16. Zinc Fingers, TALEs, and CRISPR Systems: A Comparison of Tools for Epigenome Editing.

    PubMed

    Waryah, Charlene Babra; Moses, Colette; Arooj, Mahira; Blancafort, Pilar

    2018-01-01

    The completion of genome, epigenome, and transcriptome mapping in multiple cell types has created a demand for precision biomolecular tools that allow researchers to functionally manipulate DNA, reconfigure chromatin structure, and ultimately reshape gene expression patterns. Epigenetic editing tools provide the ability to interrogate the relationship between epigenetic modifications and gene expression. Importantly, this information can be exploited to reprogram cell fate for both basic research and therapeutic applications. Three different molecular platforms for epigenetic editing have been developed: zinc finger proteins (ZFs), transcription activator-like effectors (TALEs), and the system of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) proteins. These platforms serve as custom DNA-binding domains (DBDs), which are fused to epigenetic modifying domains to manipulate epigenetic marks at specific sites in the genome. The addition and/or removal of epigenetic modifications reconfigures local chromatin structure, with the potential to provoke long-lasting changes in gene transcription. Here we summarize the molecular structure and mechanism of action of ZF, TALE, and CRISPR platforms and describe their applications for the locus-specific manipulation of the epigenome. The advantages and disadvantages of each platform will be discussed with regard to genomic specificity, potency in regulating gene expression, and reprogramming cell phenotypes, as well as ease of design, construction, and delivery. Finally, we outline potential applications for these tools in molecular biology and biomedicine and identify possible barriers to their future clinical implementation.

  17. Ensemble des troubles causés par l'alcoolisation fœtale : lignes directrices canadiennes concernant le diagnostic

    PubMed Central

    Chudley, Albert E.; Conry, Julianne; Cook, Jocelynn L.; Loock, Christine; Rosales, Ted; LeBlanc, Nicole

    2005-01-01

    Résumé LE DIAGNOSTIC DE L'ENSEMBLE DES TROUBLES CAUSÉS PAR L'ALCOOLISATION FÉTALE (ETCAF) est complexe et l'élaboration de lignes directrices concernant le diagnostic est justifiée. Un sous-comité du Comité consultatif national de l'Agence de santé publique du Canada sur l'Ensemble des troubles causés par l'alcoolisation fœtale a examiné, analysé et intégré les méthodes de diagnostic actuelles afin de parvenir à une méthode de diagnostic normalisée faisant le consensus au Canada. L'objet du présent document est d'examiner et de clarifier l'utilisation des systèmes de diagnostic actuels et de formuler des recommandations quant à leur application pour le diagnostic des déficiences liées à l'ETCAF chez des individus de tous les âges. Les lignes directrices sont fondées sur un vaste consensus de praticiens et d'autres intervenants spécialisés dans le domaine. Ces lignes directrices ont été organisées en sept catégories, soit le dépistage et l'orientation vers les spécialistes, l'examen physique et le diagnostic différentiel, l'évaluation du comportement neurologique, le traitement et le suivi, les antécédents de consommation d'alcool de la mère pendant la grossesse, les critères du diagnostic pour le syndrome d'alcoolisation fœtale (SAF), SAF partiel et troubles neurologiques du développement liés à l'alcool, l'harmonisation de l'Institute of Medicine (IOM) et des approches du Code diagnostique à 4 chiffres. Le diagnostic exige une évaluation complète des antécédents, ainsi qu'un examen physique et du comportement neurologique, tout en recourant à une approche multidisciplinaire. Les présentes lignes directrices pour le diagnostic du syndrome d'alcoolisation fœtale et des déficiences qui y sont associées sont les premières à avoir été élaborées au Canada et elles sont fondées sur la consultation d'un grand éventail de spécialistes du diagnostic.

  18. How Shorebilly Brewing Company Won the Trademark Battle, but Lost the War: A Cautionary Tale for Entrepreneurs

    ERIC Educational Resources Information Center

    Koval, Michael R.

    2018-01-01

    This article demonstrates how the case at hand, Teal Bay Alliances, LLC v. Southbound One, Inc., can be used as the core of a business case to teach students not only the basics of trademark law, but also as a real-world cautionary tale whose moral boils down to this: lawyers and businesspeople approach legal disputes from very different…

  19. Improved regional-scale groundwater representation by the coupling of the mesoscale Hydrologic Model (mHM v5.7) to the groundwater model OpenGeoSys (OGS)

    NASA Astrophysics Data System (ADS)

    Jing, Miao; Heße, Falk; Kumar, Rohini; Wang, Wenqing; Fischer, Thomas; Walther, Marc; Zink, Matthias; Zech, Alraune; Samaniego, Luis; Kolditz, Olaf; Attinger, Sabine

    2018-06-01

    Most large-scale hydrologic models fall short in reproducing groundwater head dynamics and simulating transport process due to their oversimplified representation of groundwater flow. In this study, we aim to extend the applicability of the mesoscale Hydrologic Model (mHM v5.7) to subsurface hydrology by coupling it with the porous media simulator OpenGeoSys (OGS). The two models are one-way coupled through model interfaces GIS2FEM and RIV2FEM, by which the grid-based fluxes of groundwater recharge and the river-groundwater exchange generated by mHM are converted to fixed-flux boundary conditions of the groundwater model OGS. Specifically, the grid-based vertical reservoirs in mHM are completely preserved for the estimation of land-surface fluxes, while OGS acts as a plug-in to the original mHM modeling framework for groundwater flow and transport modeling. The applicability of the coupled model (mHM-OGS v1.0) is evaluated by a case study in the central European mesoscale river basin - Nägelstedt. Different time steps, i.e., daily in mHM and monthly in OGS, are used to account for fast surface flow and slow groundwater flow. Model calibration is conducted following a two-step procedure using discharge for mHM and long-term mean of groundwater head measurements for OGS. Based on the model summary statistics, namely the Nash-Sutcliffe model efficiency (NSE), the mean absolute error (MAE), and the interquartile range error (QRE), the coupled model is able to satisfactorily represent the dynamics of discharge and groundwater heads at several locations across the study basin. Our exemplary calculations show that the one-way coupled model can take advantage of the spatially explicit modeling capabilities of surface and groundwater hydrologic models and provide an adequate representation of the spatiotemporal behaviors of groundwater storage and heads, thus making it a valuable tool for addressing water resources and management problems.

  20. The Landscape of mtDNA Modifications in Cancer: A Tale of Two Cities.

    PubMed

    Hertweck, Kate L; Dasgupta, Santanu

    2017-01-01

    Mitochondria from normal and cancerous cells represent a tale of two cities, wherein both execute similar processes but with different cellular and molecular effects. Given the number of reviews currently available which describe the functional implications of mitochondrial mutations in cancer, this article focuses on documenting current knowledge in the abundance and distribution of somatic mitochondrial mutations, followed by elucidation of processes which affect the fate of mutations in cancer cells. The conclusion includes an overview of translational implications for mtDNA mutations, as well as recommendations for future research uniting mitochondrial variants and tumorigenesis.

  1. A tale of four surveys:What have we learned about the variable sky?

    NASA Astrophysics Data System (ADS)

    Howell, S. B.

    2008-03-01

    Four tales concerning a set of photometric imaging surveys are spun. The reader is lead through a brief description of each survey and major results are presented. The four surveys are summarized in a few simple "rules": 1) The fraction of point sources that are variable with respect to those that are found to be constant, increases as a power law as the photometric precision of the survey improves, and 2) This fact can be simply formulated as a power law function granting the user a predictive power.

  2. Tales from the hundred year history of the American Physical Society

    NASA Astrophysics Data System (ADS)

    Lustig, H.

    1999-05-01

    The tale to be told on this occasion - a tale only slightly out of school - is that of the punctuated evolution of the APS in pursuing its hundred years old mission, "the advancement and diffusion of the knowledge of physics". For long periods this goal was pursued, singlemindedly and impressively, through scientfic meetings and the Society's journals. However, within a year of its founding, the APS,in concert with other scientific societies, had already "lobbied" successfully for the establishment of the Bureau of Standards. But then all was quiet on the public front until after World War II. Since that time there have been three waves of forays into the public arena. The first, which spanned the "McCarthy period", was in defense of the freedom of scientists to practice their profession across national boundaries; of the right to announce the results of their research even if they trod on powerful toes (the Astin case); and of individual physicists, such as E.U. Condon and J.Robert Oppenheimer,who had been unfairly accused and badly treated. The second wave occurred in the late sixties and early seventies when, initially much pushed by activist members, the Society's leadership came to grips with broad social issues, such as segregation in the South, the Equal Rights Amendment, and, eventually, arms control and nuclear weapons. The third immersion in public affairs, which is still very much in progress, can be characterized as worrying and speaking out on what physics can do for the country (provide authoritative studies on nuclear energy, renewables, directed energy weapons, etc.) and what the country can do for physics (provide more money). Although lobbying for better funding is still a relatively minor occupation of the Society, it raises the question how physics -an elitist pursuit -can be truthfully and effectively "sold" in a democratic and egalitarian society.

  3. Enhanced biofiltration of O&G produced water comparing granular activated carbon and nutrients.

    PubMed

    Riley, Stephanie M; Ahoor, Danika C; Cath, Tzahi Y

    2018-05-31

    Large volumes of water are required for the development of unconventional oil and gas (O&G) wells. Water scarcity coupled with seismicity induced by deep-well disposal promote new O&G wastewater management strategies, specifically treatment and reuse. One technology that has been proven effective for removal of organic matter and solids is biologically active filtration (BAF) with granular active carbon (GAC); however, further optimization is needed to enhance BAF performance. This study evaluated three GAC media (one spent and two new) and two nutrient-mix supplements for enhanced removal of chemical oxygen demand (COD) and dissolved organic carbon (DOC). Biofilm development was also monitored and correlated to BAF performance. The spent GAC with extant biofilm quickly acclimated to PW and demonstrated up to 92% DOC removal (81% COD) in 24h, while little impact by nutrient addition was observed. In addition, virgin GAC was slow to establish a biofilm, indicating that appropriate GAC selection and pre-developed biofilm is critical for efficient BAF performance. Furthermore, the production of high quality BAF effluent (less than 20mg/L DOC) presents the opportunity to apply BAF as a pretreatment for subsequent desalination-expanding the potential for reuse applications of PW. Copyright © 2017. Published by Elsevier B.V.

  4. The tale of two stories: Challenges and innovations in breast cancer management.

    PubMed

    Henry-Tillman, Ronda S

    2018-06-01

    The keynote address The Tale of Two Stories: Challenges and Innovations in Breast Cancer Management presented on March 19-20, 2017 at the celebratory Festschrift Lecture in honor of the great Dr. LaSalle Leffall's on behalf of his impact and contributions to the field of Breast cancer science and treatment as a leader, surgeon, and mentor. This presentation and follow up opinion paper in the field of Breast Disease highlights the challenges that have baffled us and the innovations that have changed and translated into outcomes and those that have not. Where do they parallel and what are the gaps? Copyright © 2018. Published by Elsevier Inc.

  5. Transgressive sexualities: politics of pleasure and desire in Kamasutra: a tale of love and fire.

    PubMed

    Lohani-Chase, Rama

    2012-01-01

    Utilizing feminist film theory, critical reviews, and viewer responses, this article examines visual representations of transgressive sexuality in two diasporic Indian women's films: Kamasutra: A Tale of Love by Mira Nair, and Fire by Deepa Mehta. The article draws from research on ancient discourses on sexuality in India to argue that contemporary constructions of women's sexuality in South Asia are not devoid of patriarchal and fundamentalist cultural politics of representation. Copyright © Taylor & Francis Group, LLC

  6. Genome-wide specificity of DNA binding, gene regulation, and chromatin remodeling by TALE- and CRISPR/Cas9-based transcriptional activators

    PubMed Central

    Polstein, Lauren R.; Perez-Pinera, Pablo; Kocak, D. Dewran; Vockley, Christopher M.; Bledsoe, Peggy; Song, Lingyun; Safi, Alexias; Crawford, Gregory E.; Reddy, Timothy E.; Gersbach, Charles A.

    2015-01-01

    Genome engineering technologies based on the CRISPR/Cas9 and TALE systems are enabling new approaches in science and biotechnology. However, the specificity of these tools in complex genomes and the role of chromatin structure in determining DNA binding are not well understood. We analyzed the genome-wide effects of TALE- and CRISPR-based transcriptional activators in human cells using ChIP-seq to assess DNA-binding specificity and RNA-seq to measure the specificity of perturbing the transcriptome. Additionally, DNase-seq was used to assess genome-wide chromatin remodeling that occurs as a result of their action. Our results show that these transcription factors are highly specific in both DNA binding and gene regulation and are able to open targeted regions of closed chromatin independent of gene activation. Collectively, these results underscore the potential for these technologies to make precise changes to gene expression for gene and cell therapies or fundamental studies of gene function. PMID:26025803

  7. The Study of Externalizing and Internalizing Behaviours in Greek, Russian, Indian, and Chinese Children Using the Fairy Tale Test

    ERIC Educational Resources Information Center

    Savina, Elena; Coulacoglou, Carina; Sanyal, Nilanjana; Zhang, Jianxin

    2012-01-01

    The present study investigated externalizing and internalizing behaviours in Greek (n = 599), Russian (n = 596), Indian (n = 571), and Chinese (n = 376) 7- to 12-year-old children. The Fairy Tale Test was used to measure impulsive and motivated aggression, fear of aggression, anxiety, and depression. The results indicated culture-specific patterns…

  8. The Heart, Not the Face: A Civil-War-Era Tale and the Persistent Challenge of Race in Religious Education

    ERIC Educational Resources Information Center

    Shafer, Peter William

    2009-01-01

    This article analyzes the 1863 pseudo slave narrative entitled "Black and White; Or, the Heart, Not the Face" by white Northerner Jane Dunbar Chaplin. The article sets this tale within the historical and literary context of "domestic abolitionism." The logic behind the story is described as "sympathetic identification," a perspective that,…

  9. A SiPM-based isotropic-3D PET detector X'tal cube with a three-dimensional array of 1 mm(3) crystals.

    PubMed

    Yamaya, Taiga; Mitsuhashi, Takayuki; Matsumoto, Takahiro; Inadama, Naoko; Nishikido, Fumihiko; Yoshida, Eiji; Murayama, Hideo; Kawai, Hideyuki; Suga, Mikio; Watanabe, Mitsuo

    2011-11-07

    We are developing a novel, general purpose isotropic-3D PET detector X'tal cube which has high spatial resolution in all three dimensions. The research challenge for this detector is implementing effective detection of scintillation photons by covering six faces of a segmented crystal block with silicon photomultipliers (SiPMs). In this paper, we developed the second prototype of the X'tal cube for a proof-of-concept. We aimed at realizing an ultimate detector with 1.0 mm(3) cubic crystals, in contrast to our previous development using 3.0 mm(3) cubic crystals. The crystal block was composed of a 16 × 16 × 16 array of lutetium gadolinium oxyorthosilicate (LGSO) crystals 0.993 × 0.993 × 0.993 mm(3) in size. The crystals were optically glued together without inserting any reflector inside and 96 multi-pixel photon counters (MPPCs, S10931-50P, i.e. six faces each with a 4 × 4 array of MPPCs), each having a sensitive area of 3.0 × 3.0 mm(2), were optically coupled to the surfaces of the crystal block. Almost all 4096 crystals were identified through Anger-type calculation due to the finely adjusted reflector sheets inserted between the crystal block and light guides. The reflector sheets, which formed a belt of 0.5 mm width, were placed to cover half of the crystals of the second rows from the edges in order to improve identification performance of the crystals near the edges. Energy resolution of 12.7% was obtained at 511 keV with almost uniform light output for all crystal segments thanks to the effective detection of the scintillation photons.

  10. Art and Fairy Tales in an Interdisciplinary Interplay: Teaching Interventions towards Negotiation and Subversion of Gender Roles and Stereotypes

    ERIC Educational Resources Information Center

    Moula, Evangelia; Kabouropoulou, Mary

    2014-01-01

    The interdisciplinary project under discussion is suitable to be addressed to students of either primary or secondary education and it interweaves the art of painting with fairy tales. The aims of the project are: the deeper understanding of the complexity of human nature and the sensitization of students regarding gender roles and stereotypes. On…

  11. A tale of two campuses: Lessons learned in establishing a satellite campus.

    PubMed

    Penner, Charles

    2018-05-01

    "It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity." The opening line of Dickens's A Tale of Two Cities could easily be the dramatic opening line of a summary of the establishment of a satellite medical school campus in Manitoba. Reflection on my last four years as associate dean reveals that most of the descriptors in that famous sentence at one time or another were apropos. This brief essay will relate the experiences of the last four years and some of the lessons learned along the way.

  12. Tales of healthy men: male reproductive bodies in biomedicine from 'Lebensborn' to sperm banks.

    PubMed

    Kampf, Antje

    2013-01-01

    Using the example of 'sperm tales', borne out of the biomedical technologies that went hand in hand with the establishment of the 'science of man' (andrology), the article engages with the epistemic evolution of interrelated biomedical theories and concepts of what constitutes a 'healthy' reproductive male body. The article asks: how has the normative ideal male body been either perpetuated or interrogated through these tales of male reproduction at the interface between scientific and medical technologies? And how were changes to the normalization of male bodies central to clinical practices and cultural understandings of health and illness? With many aspects of the medical history of male reproduction in the 20th century still unexplored, this article will focus on the growing intervention of biomedicine to 'treat' male infertility by way of the classification, standardization and normalization of male corporeality, focusing in particular on the representation and construction of men and the male body, as reflected in medical science and practice from the second half of the 20th century onwards in Germany. The article analyses the rise in importance of sperm in biomedical investigation, including a consideration of the construction of infertility as the defining force behind concepts of 'healthy men', and examines the related conceptualization of male reproductive bodies at the crossroad between 'healthy' and 'normal'. It is argued that the ideal of male reproduction as being inherently healthy has lost ground. By the late 20th century, male bodies have become vulnerable, at least as represented in medical science and technology.

  13. "Writing Will Keep You Free": Allusions to and Recreations of the Fairy Tale Heroine in "The House on Mango Street"

    ERIC Educational Resources Information Center

    Wissman, Kelly

    2007-01-01

    This article explores how Sandra Cisneros alludes to and recasts popular fairy tales in "The House on Mango Street" to reveal their troubled legacy in the lives of many women in the novel. Drawing upon Latina feminist theory and Cisneros's autobiographical writing, this article posits that the main character Esperanza's alternative "happily ever…

  14. Using the Big Six Research Process. The Coconut Crab from Guam and Other Stories: Writing Myths, Fables, and Tall Tales.

    ERIC Educational Resources Information Center

    Jansen, Barbara A.; Culpepper, Susan N.

    1996-01-01

    Using the Big Six research process, students at Live Oak Elementary (Round Rock, TX) supplemented information from traditional print and electronic sources with e-mail exchanges around the world to complete a library research collaborative project culminating in an original folk tale. Describes the Big Six process and how it was applied. (PEN)

  15. A dysphoric's TALE: The relationship between the self-reported functions of autobiographical memory and symptoms of depression.

    PubMed

    Grace, Lydia; Dewhurst, Stephen A; Anderson, Rachel J

    2016-10-01

    Autobiographical memory (AM) is believed to serve self, social and directive functions; however, little is known regarding how this triad of functions operates in depression. Using the Thinking About Life Experiences questionnaire [Bluck, S., & Alea, N. (2011). Crafting the TALE: Construction of a measure to assess the functions of autobiographical remembering. Memory, 19, 470-486.; Bluck, S., Alea, N., Habermas, T., & Rubin, D. C. (2005). A TALE of three functions: The self-reported uses of autobiographical memory. Social Cognition, 23, 91-117.], two studies explored the relationship between depressive symptomology and the self-reported frequency and usefulness of AMs for self, social and directive purposes. Study 1 revealed that thinking more frequently but talking less frequently about past life events was significantly associated with higher depression scores. Recalling past events more frequently to maintain self-continuity was also significantly associated with higher depressive symptomology. However, results from Study 2 indicated that higher levels of depression were also significantly associated with less-frequent useful recollections of past life events for self-continuity purposes. Taken together, the findings suggest atypical utilisations of AM to serve self-continuity functions in depression and can be interpreted within the wider context of ruminative thought processes.

  16. Assessment of Local Biodiversity Loss in Uranium Mining-Tales And Its Projections On Global Scale

    NASA Astrophysics Data System (ADS)

    Sharshenova, D.; Zhamangulova, N.

    2015-12-01

    In Min-Kush, northern Kyrgyzstan there are 8 mining tales with an estimate of 1 961 000 tones of industrial Uranium. Local ecosystem services have declined rapidly. We analyzed a terrestrial assemblage database of Uranium mine-tale to quantify local biodiversity responses to land use and environmental changes. In the worst-affected habitats species richness reduced by 95.7%, total abundance by 60.9% and rarefaction-based richness by 72.5%. We estimate that, regional mountain ecosystem affected by this pressure reduced average within-sample richness (by 17.01%), total abundance (16.5%) and rarefaction-based richness (14.5%). Business-as-usual scenarios are the widely practiced in the region and moreover, due to economic constraints country can not afford any mitigation scenarios. We project that biodiversity loss and ecosystem service impairment will spread in the region through ground water, soil, plants, animals and microorganisms at the rate of 1km/year. Entire Tian-Shan mountain chain will be in danger within next 5-10 years. Our preliminary data shows that local people live in this area developed various forms of cancer, and the rate of premature death is as high as 40%. Strong international scientific and socio-economic partnership is needed to develop models and predictions.

  17. Genome-wide specificity of DNA binding, gene regulation, and chromatin remodeling by TALE- and CRISPR/Cas9-based transcriptional activators.

    PubMed

    Polstein, Lauren R; Perez-Pinera, Pablo; Kocak, D Dewran; Vockley, Christopher M; Bledsoe, Peggy; Song, Lingyun; Safi, Alexias; Crawford, Gregory E; Reddy, Timothy E; Gersbach, Charles A

    2015-08-01

    Genome engineering technologies based on the CRISPR/Cas9 and TALE systems are enabling new approaches in science and biotechnology. However, the specificity of these tools in complex genomes and the role of chromatin structure in determining DNA binding are not well understood. We analyzed the genome-wide effects of TALE- and CRISPR-based transcriptional activators in human cells using ChIP-seq to assess DNA-binding specificity and RNA-seq to measure the specificity of perturbing the transcriptome. Additionally, DNase-seq was used to assess genome-wide chromatin remodeling that occurs as a result of their action. Our results show that these transcription factors are highly specific in both DNA binding and gene regulation and are able to open targeted regions of closed chromatin independent of gene activation. Collectively, these results underscore the potential for these technologies to make precise changes to gene expression for gene and cell therapies or fundamental studies of gene function. © 2015 Polstein et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Theoretical predictions for α -decay chains of 118 290 -298Og isotopes using a finite-range nucleon-nucleon interaction

    NASA Astrophysics Data System (ADS)

    Ismail, M.; Adel, A.

    2018-04-01

    The α -decay half-lives of the recently synthesized superheavy nuclei (SHN) are investigated by employing the density dependent cluster model. A realistic nucleon-nucleon (NN ) interaction with a finite-range exchange part is used to calculate the microscopic α -nucleus potential in the well-established double-folding model. The calculated potential is then implemented to find both the assault frequency and the penetration probability of the α particle by means of the Wentzel-Kramers-Brillouin (WKB) approximation in combination with the Bohr-Sommerfeld quantization condition. The calculated values of α -decay half-lives of the recently synthesized Og isotopes and its decay products are in good agreement with the experimental data. Moreover, the calculated values of α -decay half-lives have been compared with those values evaluated using other theoretical models, and it was found that our theoretical values match well with their counterparts. The competition between α decay and spontaneous fission is investigated and predictions for possible decay modes for the unknown nuclei 118 290 -298Og are presented. We studied the behavior of the α -decay half-lives of Og isotopes and their decay products as a function of the mass number of the parent nuclei. We found that the behavior of the curves is governed by proton and neutron magic numbers found from previous studies. The proton numbers Z =114 , 116, 108, 106 and the neutron numbers N =172 , 164, 162, 158 show some magic character. We hope that the theoretical prediction of α -decay chains provides a new perspective to experimentalists.

  19. The Monk's Tale: Nero's Nets and Caesar's Father -- An Inquiry into the Transformations of Classical Roman History in Medieval Tradition

    ERIC Educational Resources Information Center

    Waller, Martha S.

    1978-01-01

    Discusses the lack of consistent accuracy about historical figures in Chaucer's "Monk's Tale." The story of Nero fishing in the Tiber with golden nets is corroborated by many other ancient and medieval authors; however, the reference to Julius Caesar as being of lowly birth is peculiar only to Chaucer and a few medieval English authors.…

  20. Once Upon a Time, Scientific Fairy Tales Explaining Topics Related to the Discovery, Protection and Use of the Ocean

    NASA Astrophysics Data System (ADS)

    Martinez-Mendez, G.; Elyashiv, H.; Reyes-Macaya, D. A.; Jackson, R.; Tangunan, D.; Schmidt, C.; Santos, C.; Hernández-Almeida, I.; Rossel, P. E.; Tamborrino, L.; Müller Dum, D.; Wang, H.; Hohmann, S.; Duran Toro, V.; Stone, J.; Hollstein, M.; Jessen, G.; Jacobi, L.; Böhnert, S.; Ruiz-Soto, S.; Rebotim, A.; Cavaleiro, C. D.; Kirillova, V.; Liu, Y. Y.; Park, E.; Contreras, A.; Mendoza, P.; Greco, M.

    2017-12-01

    "Once Upon a Time… a Scientific Fairy Tale" is a project that aims to communicate science and promote the dialogue between scientists and the general public. An international group of young scientists working in different research fields (marine geochemistry, marine microbiology, marine geology, marine ecology) at various institutions near Bremen have written short stories (tales) with scientific content in a simple language. The target audience for these stories is adults with a connection to children. The major focus of the stories have been human impact in the oceans. The stories will be published by the end of August 2017 in an illustrated Ebook, first in English, German and Spanish. In a second phase of the project the stories will be also published in Italian, French, Chinese, Portuguese, Hebrew, Philipino, Korean, Russian and Farsi. The objective with translating the stories to so many languages is reaching the broader possible audience. Reading events of the stories will provide further platforms for their spreading. The project is one of the winner projects of the competition "Hochschulwettbewerb im Wissenschftsjahr 2016*17 - Meere un Ozeane" (see more information in http://www.hochschulwettbewerb.net/gewinnerprojekte/) of the German foundation "Wissenschaft im Dialog".

  1. Ancient DNA and the tropics: a rodent's tale.

    PubMed

    Gutiérrez-García, Tania A; Vázquez-Domínguez, Ella; Arroyo-Cabrales, Joaquín; Kuch, Melanie; Enk, Jacob; King, Christine; Poinar, Hendrik N

    2014-06-01

    Most genetic studies of Holocene fauna have been performed with ancient samples from dry and cold regions, in which preservation of fossils is facilitated and molecular damage is reduced. Ancient DNA work from tropical regions has been precluded owing to factors that limit DNA preservation (e.g. temperature, hydrolytic damage). We analysed ancient DNA from rodent jawbones identified as Ototylomys phyllotis, found in Holocene and Late Pleistocene stratigraphic layers from Loltún, a humid tropical cave located in the Yucatan peninsula. We extracted DNA and amplified six short overlapping fragments of the cytochrome b gene, totalling 666 bp, which represents an unprecedented success considering tropical ancient DNA samples. We performed genetic, phylogenetic and divergence time analyses, combining sequences from ancient and modern O. phyllotis, in order to assess the ancestry of the Loltún samples. Results show that all ancient samples fall into a unique clade that diverged prior to the divergence of the modern O. phyllotis, supporting it as a distinct Pleistocene form of the Ototylomys genus. Hence, this rodent's tale suggests that the sister group to modern O. phyllotis arose during the Miocene-Pliocene, diversified during the Pleistocene and went extinct in the Holocene. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  2. Students' Decision Steps in Meta-Cognitive Learning in Free Online Groups (MetaL-FrOG): A Case Study

    ERIC Educational Resources Information Center

    Sen Fa, Kinsley Ng; Hussin, Firuz Hussin

    2011-01-01

    What prompts the students to respond in online dialogic discussion? Why some students chose to fall out? This case study through the lens of phenomenography observation attempts to explain the five decision steps of students to respond in Meta-cognitive Learning in Free Online Groups (MetaL-FrOG) discussion. It presents a part of a research…

  3. Experimental and theoretical investigation of homogeneous gaseous reaction of CO2(g) + nH2O(g) + nNH3(g) → products (n = 1, 2).

    PubMed

    Li, Zhuangjie; Zhang, Baoquan

    2012-09-13

    Decreasing CO2 emissions into the atmosphere is key for reducing global warming. To facilitate the CO2 emission reduction efforts, our laboratory conducted experimental and theoretical investigations of the homogeneous gaseous reaction of CO2(g) + nH2O(g) + nNH3(g) → (NH4)HCO3(s)/(NH4)2CO3(s) (n = 1 and 2) using Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy and ab initio molecular orbital theory. Our FTIR-ATR experimental results indicate that (NH4)2CO3(s) and (NH4)HCO3(s) are formed as aerosol particulate matter when carbon dioxide reacts with ammonia and water in the gaseous phase at room temperature. Ab initio study of this chemical system suggested that the reaction may proceed through formation of NH3·H2O(g), NH3·CO2(g), and CO2·H2O(g) complexes. Subsequent complexes, NH3·H2O·CO2 and (NH3)2·H2O·CO2, can be formed by adding gaseous reactants to the NH3·H2O(g), NH3·CO2(g), and CO2·H2O(g) complexes, respectively. The NH3·H2O·CO2 and (NH3)2·H2O·CO2 complexes can then be rearranged to produce (NH4)HCO3 and (NH4)2CO3 as final products via a transition state, and the NH3 molecule acts as a medium accepting and donating hydrogen atoms in the rearrangement process. Our computational results also reveal that the presence of an additional water molecule can reduce the activation energy of the rearrangement process. The high activation energy predicted in the present work suggests that the reaction is kinetically not favored, and our experimental observation of (NH4)HCO3(s) and (NH4)2CO3(s) may be attributed to the high concentrations of reactants increasing the reaction rate of the title reactions in the reactor.

  4. Trimeric association of Hox and TALE homeodomain proteins mediates Hoxb2 hindbrain enhancer activity.

    PubMed

    Jacobs, Y; Schnabel, C A; Cleary, M L

    1999-07-01

    Pbx/exd proteins modulate the DNA binding affinities and specificities of Hox proteins and contribute to the execution of Hox-dependent developmental programs in arthropods and vertebrates. Pbx proteins also stably heterodimerize and bind DNA with Meis and Pknox1-Prep1, additional members of the TALE (three-amino-acid loop extension) superclass of homeodomain proteins that function on common genetic pathways with a subset of Hox proteins. In this study, we demonstrated that Pbx and Meis bind DNA as heterotrimeric complexes with Hoxb1 on a genetically defined Hoxb2 enhancer, r4, that mediates the cross-regulatory transcriptional effects of Hoxb1 in vivo. The DNA binding specificity of the heterotrimeric complex for r4 is mediated by a Pbx-Hox site in conjunction with a distal Meis site, which we showed to be required for ternary complex formation and Meis-enhanced transcription. Formation of heterotrimeric complexes in which all three homeodomains bind their cognate DNA sites is topologically facilitated by the ability of Pbx and Meis to interact through their amino termini and bind DNA without stringent half-site orientation and spacing requirements. Furthermore, Meis site mutation in the Hoxb2 enhancer phenocopies Pbx-Hox site mutation to abrogate enhancer-directed expression of a reporter transgene in the murine embryonic hindbrain, demonstrating that DNA binding by all three proteins is required for trimer function in vivo. Our data provide in vitro and in vivo evidence for the combinatorial regulation of Hox and TALE protein functions that are mediated, in part, by their interdependent DNA binding activities as ternary complexes. As a consequence, Hoxb1 employs Pbx and Meis-related proteins, as a pair of essential cofactors in a higher-order molecular complex, to mediate its transcriptional effects on an endogenous Hox response element.

  5. Trimeric Association of Hox and TALE Homeodomain Proteins Mediates Hoxb2 Hindbrain Enhancer Activity

    PubMed Central

    Jacobs, Yakop; Schnabel, Catherine A.; Cleary, Michael L.

    1999-01-01

    Pbx/exd proteins modulate the DNA binding affinities and specificities of Hox proteins and contribute to the execution of Hox-dependent developmental programs in arthropods and vertebrates. Pbx proteins also stably heterodimerize and bind DNA with Meis and Pknox1-Prep1, additional members of the TALE (three-amino-acid loop extension) superclass of homeodomain proteins that function on common genetic pathways with a subset of Hox proteins. In this study, we demonstrated that Pbx and Meis bind DNA as heterotrimeric complexes with Hoxb1 on a genetically defined Hoxb2 enhancer, r4, that mediates the cross-regulatory transcriptional effects of Hoxb1 in vivo. The DNA binding specificity of the heterotrimeric complex for r4 is mediated by a Pbx-Hox site in conjunction with a distal Meis site, which we showed to be required for ternary complex formation and Meis-enhanced transcription. Formation of heterotrimeric complexes in which all three homeodomains bind their cognate DNA sites is topologically facilitated by the ability of Pbx and Meis to interact through their amino termini and bind DNA without stringent half-site orientation and spacing requirements. Furthermore, Meis site mutation in the Hoxb2 enhancer phenocopies Pbx-Hox site mutation to abrogate enhancer-directed expression of a reporter transgene in the murine embryonic hindbrain, demonstrating that DNA binding by all three proteins is required for trimer function in vivo. Our data provide in vitro and in vivo evidence for the combinatorial regulation of Hox and TALE protein functions that are mediated, in part, by their interdependent DNA binding activities as ternary complexes. As a consequence, Hoxb1 employs Pbx and Meis-related proteins, as a pair of essential cofactors in a higher-order molecular complex, to mediate its transcriptional effects on an endogenous Hox response element. PMID:10373562

  6. Off and back-on again: a tumor suppressor's tale.

    PubMed

    Acosta, Jonuelle; Wang, Walter; Feldser, David M

    2018-06-01

    Tumor suppressor genes play critical roles orchestrating anti-cancer programs that are both context dependent and mechanistically diverse. Beyond canonical tumor suppressive programs that control cell division, cell death, and genome stability, unexpected tumor suppressor gene activities that regulate metabolism, immune surveillance, the epigenetic landscape, and others have recently emerged. This diversity underscores the important roles these genes play in maintaining cellular homeostasis to suppress cancer initiation and progression, but also highlights a tremendous challenge in discerning precise context-specific programs of tumor suppression controlled by a given tumor suppressor. Fortunately, the rapid sophistication of genetically engineered mouse models of cancer has begun to shed light on these context-dependent tumor suppressor activities. By using techniques that not only toggle "off" tumor suppressor genes in nascent tumors, but also facilitate the timely restoration of gene function "back-on again" in disease specific contexts, precise mechanisms of tumor suppression can be revealed in an unbiased manner. This review discusses the development and implementation of genetic systems designed to toggle tumor suppressor genes off and back-on again and their potential to uncover the tumor suppressor's tale.

  7. Horror films: tales to master terror or shapers of trauma?

    PubMed

    Ballon, Bruce; Leszcz, Molyn

    2007-01-01

    The authors review the literature of cinematic-related psychiatric case reports and report the case of a 22-year-old woman who presented with intrusive thoughts of demonic possession and flashbacks of the film The Exorcist. Cinematic neurosis may be considered a form of psychological crisis shaped by exposure to a film narrative that is emotionally and culturally significant to the individual. The structure of horror films are examined from the perspectives of trauma theory, narrative theory, and borderline personality organization theories, using the film The Exorcist as an example. Within this framework, the horror film can be seen as a cultural tale that provides a mechanism for attempting mastery over anxieties involving issues of separation, loss, autonomy, and identity. An individual will identify with narrative elements that resonate in personal life experiences and cultural factors embedded within the film, which carry levels of either stress that will be mastered, or act as a trauma to the viewer. The outcome of this exposure is related to how the individual's personality structure is organized in combination with the stresses they are experiencing.

  8. TALE nickase mediates high efficient targeted transgene integration at the human multi-copy ribosomal DNA locus.

    PubMed

    Wu, Yong; Gao, Tieli; Wang, Xiaolin; Hu, Youjin; Hu, Xuyun; Hu, Zhiqing; Pang, Jialun; Li, Zhuo; Xue, Jinfeng; Feng, Mai; Wu, Lingqian; Liang, Desheng

    2014-03-28

    Although targeted gene addition could be stimulated strikingly by a DNA double strand break (DSB) created by either zinc finger nucleases (ZFNs) or TALE nucleases (TALENs), the DSBs are really mutagenic and toxic to human cells. As a compromised solution, DNA single-strand break (SSB) or nick has been reported to mediate high efficient gene addition but with marked reduction of random mutagenesis. We previously demonstrated effective targeted gene addition at the human multicopy ribosomal DNA (rDNA) locus, a genomic safe harbor for the transgene with therapeutic potential. To improve the transgene integration efficiency by using TALENs while lowering the cytotoxicity of DSBs, we created both TALENs and TALE nickases (TALENickases) targeting this multicopy locus. A targeting vector which could integrate a GFP cassette at the rDNA locus was constructed and co-transfected with TALENs or TALENickases. Although the fraction of GFP positive cells using TALENs was greater than that using TALENickases during the first few days after transfection, it reduced to a level less than that using TALENickases after continuous culture. Our findings showed that the TALENickases were more effective than their TALEN counterparts at the multi-copy rDNA locus, though earlier studies using ZFNs and ZFNickases targeting the single-copy loci showed the reverse. Besides, TALENickases mediated the targeted integration of a 5.4 kb fragment at a frequency of up to 0.62% in HT1080 cells after drug selection, suggesting their potential application in targeted gene modification not being limited at the rDNA locus. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. SU-D-9A-01: Listmode-Driven Optimal Gating (OG) Respiratory Motion Management: Potential Impact On Quantitative PET Imaging

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

    Lee, K; Hristov, D

    2014-06-01

    Purpose: To evaluate the potential impact of listmode-driven amplitude based optimal gating (OG) respiratory motion management technique on quantitative PET imaging. Methods: During the PET acquisitions, an optical camera tracked and recorded the motion of a tool placed on top of patients' torso. PET event data were utilized to detect and derive a motion signal that is directly coupled with a specific internal organ. A radioactivity-trace was generated from listmode data by accumulating all prompt counts in temporal bins matching the sampling rate of the external tracking device. Decay correction for 18F was performed. The image reconstructions using OG respiratorymore » motion management technique that uses 35% of total radioactivity counts within limited motion amplitudes were performed with external motion and radioactivity traces separately with ordered subset expectation maximization (OSEM) with 2 iterations and 21 subsets. Standard uptake values (SUVs) in a tumor region were calculated to measure the effect of using radioactivity trace for motion compensation. Motion-blurred 3D static PET image was also reconstructed with all counts and the SUVs derived from OG images were compared with SUVs from 3D images. Results: A 5.7 % increase of the maximum SUV in the lesion was found for optimal gating image reconstruction with radioactivity trace when compared to a static 3D image. The mean and maximum SUVs on the image that was reconstructed with radioactivity trace were found comparable (0.4 % and 4.5 % increase, respectively) to the values derived from the image that was reconstructed with external trace. Conclusion: The image reconstructed using radioactivity trace showed that the blurring due to the motion was reduced with impact on derived SUVs. The resolution and contrast of the images reconstructed with radioactivity trace were comparable to the resolution and contrast of the images reconstructed with external respiratory traces. Research supported by

  10. Tal Como Somos/Just As We Are: An Educational Film to Reduce Stigma towards Gay and Bisexual Men, Transgender Individuals & Persons Living with HIV/AIDS

    PubMed Central

    Ramirez-Valles, Jesus; Kuhns, Lisa M.; Manjarrez, Dianna

    2013-01-01

    In this paper we describe the development and dissemination of a film-based educational intervention to reduce negative attitudes towards gay and bisexual men and transgender women (GBT) and people living with HIV/AIDS (PLWHA) in Latino communities, with a focus on youth. The intervention, Tal Como Somos/Just as We Are, is based on stigma and attribution theories, extensive formative research, and community input. Evaluation findings among educators and school youth suggest the film has the potential to effectively impact attitudes towards GBT and PLWHA. The film and intervention are being disseminated using diffusion of innovations theory through community-based organizations, schools, television broadcasting and film festivals. PMID:24377496

  11. The Three Tales Chosen, the Establishment of the Texts and the Charting of Deviations, with a Collation of the "Original Tales," the Check Translations, and the Danish and Turkish Texts. Fairytale: An Interdisciplinary Turco-Danish Study of the Collective v. the Individual Nature of the Response to Literature. Report No. 11. Revised.

    ERIC Educational Resources Information Center

    Dollerup, Cay; And Others

    Part of the interdisciplinary Turko-Danish Fairytale Project, this paper provides information about the three fairy tales chosen for study: "The Snake, the Fox, and the Man,""The Gold Apple," and "Per Smed's Whip." Various sections of the paper contain descriptions of the following: (1) the selection procedures, (2)…

  12. A Tale of Blue Rain Cafe: A Study on the Online Narrative Construction about a Community of English Learners on the Chinese Mainland

    ERIC Educational Resources Information Center

    Gao, Xuesong

    2007-01-01

    The study analyzes a strand of online discussion messages entitled "a Tale of Blue Rain Cafe" from an online community of English learners on the Chinese mainland. The strand of messages was part of the collective reflection made by members of an English learning club on their participation. Using sociocultural learning theory, the paper…

  13. Chemical and Antimicrobial Analyses of Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood, an Endemic of the Western Balkan.

    PubMed

    Tadić, Vanja; Oliva, Alessandra; Božović, Mijat; Cipolla, Alessia; De Angelis, Massimiliano; Vullo, Vincenzo; Garzoli, Stefania; Ragno, Rino

    2017-08-23

    A comprehensive study on essential oil and different solvent extracts of Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood (Lamiaceae) from Montenegro is reported. The gas chromatography-mass spectrometry analysis of the essential oil revealed a total of 43 components with bicyclogermacrene (23.8%), germacrene D (8%), ( E )-caryophyllene (7.9%) and spathulenol (5.5%) as the major ones. Sesquiterpenoid group was found to be the most dominant one (64.8%), with 19.9% of the oxygenated forms. In the crude methanol extract of the investigated plant, obtained by Sohhlet exraction, the total phenol content was 14.7 ± 0.4 mg of GA/g, the total flavonoids were 0.29 ± 0.03% expressed as hyperoside percentage, whereas the total tannins content was 0.22 ± 0.04% expressed as pyrogallol percentage. For the antimicrobial activity determination, the following microorganisms have been used: methicillin-susceptible Staphylococcus aureus (MSSA (American Type Culture Collection (ATCC) 29213)) and methicillin-resistant S. aureus (MRSA (clinical strain)), Escherichia coli (ATCC 25922), carbapenem-susceptible Klebsiella pneumoniae (clinical strain), carbapenem-resistant K. pneumoniae (clinical strain) and Candida albicans (ATCC 14053). The essential oil showed high potency against MSSA and MRSA, both at high (~5 × 10⁵ CFU/mL) and low (~5 × 10³ CFU/mL) inoculum. With respect to MSSA, the minimal inhibitory concentration (MIC) value was 0.307 mg/mL, with bactericidal activity obtained at 0.615 mg/mL, while, in the case of MRSA, the MIC and minimal bactericidal concentration (MBC) values were 0.076 and 0.153 mg/mL, respectively. Regarding anti- Candida albicans activity, the MIC value was 2.46 mg/mL without reaching fungicidal activity. In addition to the observed essential oil efficacy, different solvent extracts were analyzed for their antimicrobial activity. Similarly to the essential oil, thehighest efficacy was observed against both MSSA and MRSA strains, at high and

  14. Transformative Narrative Therapy: How Transforming a Personal Life Story into Fairy-Tale Format Impacts Measures of Health and Well-Being in Older Adults

    ERIC Educational Resources Information Center

    Oumarou, Sahibou

    2013-01-01

    Recalling and reframing a personal life story in the form of a fairy tale, then engaging in a practice on meditation and reflecting on it, is one way older adults can relieve their positive experience and thereby impact their mental and emotional health and well-being. Although prior research has established the benefits of narrative therapy (NT)…

  15. Development of the New DAQ System for the SD Array of TA×4 and TALE

    NASA Astrophysics Data System (ADS)

    Takahashi, Yuichi; Sahara, Ryosuke; Konishi, Shogo; Goto, Takashi; Ogio, Shoichi

    The data acquisition (DAQ) system for the surface detector (SD) arrays of TA×4 and TALE will be presented. Each SD records digital signals with 50 MHz FADCs and sends the data to a central communication center (of the "communication tower") via a wireless network system. The technique employed here is based on the currently-running DAQ system of the Telescope Array, and there are some improvements including i) replacement of a wireless LAN module with a custom protocol to another with TCP/IP, and ii) replacement of the "tower electronics" to a generic Linux board PC of Raspberry Pi Type II B. The details and performance of the new DAQ system are described below.

  16. A Tale of Two Hemispheres: Field Studies of Aerosols and Marine Stratocumulus Clouds (451st Brookhaven Lecture)

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

    Lee, Yin-Nan

    2009-05-13

    By reflecting sunlight, clouds may be mitigating the warming effect of greenhouse gases in the Earth's atmosphere. To discuss the roll that aerosol particles play in the cooling mechanism of clouds, Chemist Yin-Nan Lee of the Atmospheric Sciences Division of the Environmental Sciences Department will discuss “A Tale of Two Hemispheres: Field Studies of Aerosols and Marine Stratocumulus Clouds” during the 451st Brookhaven Lecture, beginning 4 p.m. on Wednesday 13 May in Berkner Hall. During his lecture, Dr. Lee will discuss his findings from collaborative studies of stratocumulus clouds over the coastal waters of California and Chile.

  17. Old Wives, the Same Man, and a Baby: Location and Family as the Foundation of Home in "Tales of Burning Love" and "Bingo Palace"

    ERIC Educational Resources Information Center

    Wilson, Jonathan

    2012-01-01

    In this article, the author discusses two books ("Tales of Burning Love" and "Bingo Palace" by Louise Erdrich) that highlight location and family as the foundation of home. The two novels suggest that "home" must be revised to include, negotiate, and, at times, embrace tenets of Western ideology in order to find or secure one's home. While various…

  18. Tal Como Somos/just as we are: an educational film to reduce stigma toward gay and bisexual men, transgender individuals, and persons living with HIV/AIDS.

    PubMed

    Ramirez-Valles, Jesus; Kuhns, Lisa M; Manjarrez, Dianna

    2014-04-01

    In this article, the authors describe the development and dissemination of a film-based educational intervention to reduce negative attitudes toward gay and bisexual men, transgender women, and people living with HIV/AIDS in Latino communities, with a focus on youth. The intervention, Tal Como Somos/Just as We Are, is based on stigma and attribution theories, extensive formative research, and community input. Evaluation findings among educators and school youth suggest the film has the potential to effectively influence attitudes toward gay and bisexual men, transgender women, and people living with HIV/AIDS. The film and intervention are being disseminated using diffusion of innovations theory through community-based organizations, schools, television broadcasting, and film festivals.

  19. A Single-Molecule View of Genome Editing Proteins: Biophysical Mechanisms for TALEs and CRISPR/Cas9.

    PubMed

    Cuculis, Luke; Schroeder, Charles M

    2017-06-07

    Exciting new advances in genome engineering have unlocked the potential to radically alter the treatment of human disease. In this review, we discuss the application of single-molecule techniques to uncover the mechanisms behind two premier classes of genome editing proteins: transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system (Cas). These technologies have facilitated a striking number of gene editing applications in a variety of organisms; however, we are only beginning to understand the molecular mechanisms governing the DNA editing properties of these systems. Here, we discuss the DNA search and recognition process for TALEs and Cas9 that have been revealed by recent single-molecule experiments.

  20. Cuentos Folkloricos Mexicanos para Todos los Ninos. Serie de Literatura Bilingue para Ninos (Folkloric Tales from Mexico for All Children. Children's Bilingual Literature Series).

    ERIC Educational Resources Information Center

    Ponce, Suanna Gilman

    Six short Mexican folk tales for children are presented in Spanish and English. Each version is presented in its own booklet. The stories are illustrated with full-page black and white drawings. "The Man Who Owned the Bees" is a story about four boys who encounter Xachan'achin, the owner of the bees in the forest. "The Magic Lady of the Water" is…

  1. Service users' self-narratives on their journey from shame to pride: tales of transition.

    PubMed

    Natland, Sidsel; Celik, Hilde Dalen

    2015-01-01

    As part of a course on changing attitudes developed by KREM, a Norwegian service user organization, narratives are used to explore and understand identity formation. The process is based on the role of shame in the lives of those whose life experiences lead to a reliance on government social benefits to sustain themselves. Shame is identified as an obstacle that affects everyday life and undermines one's capacity to take actions that can lead to and support self-sufficiency. Exploring oneself through the construction of the fairy tale can provide service users with a renewed sense of empowerment. Using identity formation and the concept of shame as the conceptual framework, this analysis focuses on the use of narratives to construct and interpret stories. It concludes with both practice and research implications of using narratives to acquire an understanding and sensitivity to service user perspectives.

  2. Comparative analysis of chimeric ZFP-, TALE- and Cas9-piggyBac transposases for integration into a single locus in human cells.

    PubMed

    Luo, Wentian; Galvan, Daniel L; Woodard, Lauren E; Dorset, Dan; Levy, Shawn; Wilson, Matthew H

    2017-08-21

    Integrating DNA delivery systems hold promise for many applications including treatment of diseases; however, targeted integration is needed for improved safety. The piggyBac (PB) transposon system is a highly active non-viral gene delivery system capable of integrating defined DNA segments into host chromosomes without requiring homologous recombination. We systematically compared four different engineered zinc finger proteins (ZFP), four transcription activator-like effector proteins (TALE), CRISPR associated protein 9 (SpCas9) and the catalytically inactive dSpCas9 protein fused to the amino-terminus of the transposase enzyme designed to target the hypoxanthine phosphoribosyltransferase (HPRT) gene located on human chromosome X. Chimeric transposases were evaluated for expression, transposition activity, chromatin immunoprecipitation at the target loci, and targeted knockout of the HPRT gene in human cells. One ZFP-PB and one TALE-PB chimera demonstrated notable HPRT gene targeting. In contrast, Cas9/dCas9-PB chimeras did not result in gene targeting. Instead, the HPRT locus appeared to be protected from transposon integration. Supplied separately, PB permitted highly efficient isolation of Cas9-mediated knockout of HPRT, with zero transposon integrations in HPRT by deep sequencing. In summary, these tools may allow isolation of 'targeted-only' cells, be utilized to protect a genomic locus from transposon integration, and enrich for Cas9-mutated cells. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

  3. Teeth Tales: a community-based child oral health promotion trial with migrant families in Australia

    PubMed Central

    Gibbs, Lisa; Waters, Elizabeth; Christian, Bradley; Gold, Lisa; Young, Dana; de Silva, Andrea; Calache, Hanny; Gussy, Mark; Watt, Richard; Riggs, Elisha; Tadic, Maryanne; Hall, Martin; Gondal, Iqbal; Pradel, Veronika; Moore, Laurence

    2015-01-01

    Objectives The Teeth Tales trial aimed to establish a model for child oral health promotion for culturally diverse communities in Australia. Design An exploratory trial implementing a community-based child oral health promotion intervention for Australian families from migrant backgrounds. Mixed method, longitudinal evaluation. Setting The intervention was based in Moreland, a culturally diverse locality in Melbourne, Australia. Participants Families with 1–4-year-old children, self-identified as being from Iraqi, Lebanese or Pakistani backgrounds residing in Melbourne. Participants residing close to the intervention site were allocated to intervention. Intervention The intervention was conducted over 5 months and comprised community oral health education sessions led by peer educators and follow-up health messages. Outcome measures This paper reports on the intervention impacts, process evaluation and descriptive analysis of health, knowledge and behavioural changes 18 months after baseline data collection. Results Significant differences in the Debris Index (OR=0.44 (0.22 to 0.88)) and the Modified Gingival Index (OR=0.34 (0.19 to 0.61)) indicated increased tooth brushing and/or improved toothbrushing technique in the intervention group. An increased proportion of intervention parents, compared to those in the comparison group reported that they had been shown how to brush their child's teeth (OR=2.65 (1.49 to 4.69)). Process evaluation results highlighted the problems with recruitment and retention of the study sample (275 complete case families). The child dental screening encouraged involvement in the study, as did linking attendance with other community/cultural activities. Conclusions The Teeth Tales intervention was promising in terms of improving oral hygiene and parent knowledge of tooth brushing technique. Adaptations to delivery of the intervention are required to increase uptake and likely impact. A future cluster randomised controlled trial

  4. Teeth Tales: a community-based child oral health promotion trial with migrant families in Australia.

    PubMed

    Gibbs, Lisa; Waters, Elizabeth; Christian, Bradley; Gold, Lisa; Young, Dana; de Silva, Andrea; Calache, Hanny; Gussy, Mark; Watt, Richard; Riggs, Elisha; Tadic, Maryanne; Hall, Martin; Gondal, Iqbal; Pradel, Veronika; Moore, Laurence

    2015-06-11

    The Teeth Tales trial aimed to establish a model for child oral health promotion for culturally diverse communities in Australia. An exploratory trial implementing a community-based child oral health promotion intervention for Australian families from migrant backgrounds. Mixed method, longitudinal evaluation. The intervention was based in Moreland, a culturally diverse locality in Melbourne, Australia. Families with 1-4-year-old children, self-identified as being from Iraqi, Lebanese or Pakistani backgrounds residing in Melbourne. Participants residing close to the intervention site were allocated to intervention. The intervention was conducted over 5 months and comprised community oral health education sessions led by peer educators and follow-up health messages. This paper reports on the intervention impacts, process evaluation and descriptive analysis of health, knowledge and behavioural changes 18 months after baseline data collection. Significant differences in the Debris Index (OR=0.44 (0.22 to 0.88)) and the Modified Gingival Index (OR=0.34 (0.19 to 0.61)) indicated increased tooth brushing and/or improved toothbrushing technique in the intervention group. An increased proportion of intervention parents, compared to those in the comparison group reported that they had been shown how to brush their child's teeth (OR=2.65 (1.49 to 4.69)). Process evaluation results highlighted the problems with recruitment and retention of the study sample (275 complete case families). The child dental screening encouraged involvement in the study, as did linking attendance with other community/cultural activities. The Teeth Tales intervention was promising in terms of improving oral hygiene and parent knowledge of tooth brushing technique. Adaptations to delivery of the intervention are required to increase uptake and likely impact. A future cluster randomised controlled trial would provide strongest evidence of effectiveness if appropriate to the community, cultural and

  5. Beauty is in the Eye of the Beholder: A Tale of Strategic Context and Operational Art in Iraq, 2004-2008

    DTIC Science & Technology

    2012-05-17

    throughout Iraq to cities such as Tal Afar, Baghdad, Mosul, Baqubah, and Ar Ramadi. However, in their attempt to control Anbar Province, al Qaeda in Iraq ...conflicts only grew stronger and by the beginning of 2006, Iraq was on the verge of civil war due to systematic terrorist attacks by al Qaeda in Iraq and...sec. Middle East, http://www.nytimes.com/2011/ 12 /16/world/middleeast/panetta-in-baghdad-for- iraq -military-handover- ceremony.html?pagewanted=all

  6. Tales of resistance and other emancipatory functions of storytelling.

    PubMed

    Grassley, Jane S; Nelms, Tommie P

    2009-11-01

    Tales of resistance and other emancipatory functions of storytelling. This paper is the report of a study to explore how the process of storytelling might facilitate women's emancipatory knowing, using examples from women's breastfeeding stories. Storytelling, as an interactive process, can give women a way to explain pivotal life events, justify choices, examine reality and find meaning in experiences. Emancipatory functions of storytelling have been identified as contextual grounding, bonding with others, validating and affirming experiences, venting and catharsis, resisting oppression and educating others. Secondary data analysis was conducted in 2008 on breastfeeding stories originally gathered from 13 women from 2002 to 2004 for a feminist hermeneutic study of maternal breastfeeding confidence. The stories were re-examined through the lens of the emancipatory functions of storytelling. Illustrations of contextual grounding, validating and affirming experiences, venting and catharsis and acts of resistance were found in the breastfeeding stories and presented as exemplars of emancipatory knowing. Women revealed the difficulties they encountered breastfeeding, transforming these experiences as they discovered their meaning. They described collisions that occurred when personal, familial, healthcare professionals' or cultural expectations differed from their experience. The stories suggested possible liberation from old ideologies about breastfeeding as women redefined the difficulties they encountered. Storytelling has potential as a simple, yet profound, and powerful emancipatory intervention which nurses can use to help women in their care make sense of and transform experiences of health and illness. Storytelling may have global implications for nursing practice and research.

  7. Tale taming radioactive fears: Linking nuclear waste disposal to the "continuum of the good".

    PubMed

    Yli-Kauhaluoma, Sari; Hänninen, Hannu

    2014-04-01

    We examine how the constructor of the world's first repository for the final disposal of spent nuclear fuel in Eurajoki, Finland, aims to shape lay understanding of the facility's risks and to tame the nuclear fears of the local community by producing positive associations, imagery and tales. Our empirical material consists of the constructor's newsletters targeted mainly at the local residents. In the narrative analysis, we identified a storyline where the construction of the repository is linked into the "continuum of the good" in the municipality of the construction site and the surrounding areas. The storyline consists of five different themes all emphasizing the "continuum of the good" in the area: cultural heritage, well-being, developing expertise, natural environment, and local families. Our study contributes to the literature on pro-nuclear storytelling by showing how the inclination is towards narratives that are constructed around local symbols, cultural landmarks, and institutions.

  8. Circulating filarial antigen in the hydrocele fluid from individuals living in a bancroftian filariasis area - Recife, Brazil: detected by the monoclonal antibody Og4C3-assay.

    PubMed

    Rocha, Abraham; Lima, Guilherme; Medeiros, Zulma; Aguiar-Santos, Ana; Alves, Sandra; Montarroyos, Ulisses; Oliveira, Paula; Béliz, Fátima; Netto, Maria José; Furtado, André

    2004-02-01

    The purpose of this study was to examine the circulating filarial antigen (CFA) detected by the monoclonal antibody (mAb) Og4C3-ELISA in paired samples of serum and hydrocele fluid from 104 men with hydrocele, living in an endemic area of Wuchereria bancrofti. Nocturnal blood specimens were filtered and examined for microfilariae (MF) and ultrasound was used in order to identify the presence of adult worms (the filaria dance sign - FDS) in the lymphatic vessels of the scrotal area. Four groups were selected according to their parasitological status: group I - 71 MF- and FDS-; group II - 21 MF+ and FDS+; group III - 10 MF- and FDS+ and group IV- 2 MF+ and FDS-. CFA was identified simultaneously (fluid and serum) in 11 (15.5%), 21 (100%), 3 (30%), and 1 (50%) in groups I, II, III, and IV, respectively. In despite of high CFA+ level (antigen Og4C3) units/ml, the Geometrical Mean (GM) = 2696) in the sera of these 36/104 paired samples, when compared to the hydrocele fluid, (GM = 1079), showed a very good correlation between the CFA level in the serum and CFA level in the fluid (r = 0.731). CFA level in the serum of the 23 microfilaremics (groups II and IV) was extremely high (GM = 4189) and was correlated with MF density (r = 0.442). These findings report for the first time the potential alternative use of the hydrocele fluid to investigate CFA using the mAb Og4C3-ELISA.

  9. Gondwana Tales: an inquiry approach to plate tectonics

    NASA Astrophysics Data System (ADS)

    Domènech Casal, Jordi

    2014-05-01

    Plate tectonics and its effects on the constitution of seas and continents are key models in science education. Fossil evidences are usually taught in demostrative key when Wegener's discoverings about Pangea are introduced. In order to introduce inquiry-based science education (IBSE) approaches to this topic, we propose "Gondwana Tales", an activity where students are asked to use fossil data to reconstruct the geologic history of an imaginary planet. Grouped in independent teams, each team is furnished with stratigraphic columns from several sites containing faunistic successions of real organisms existing in the past in Earth. Students are told to reconstruct a model of the evolution of the continents, by making calculations of relative ages of the fossils, and relating each fossil to a geologic era. The different teams have incomplete and complementary information. After a first step where they have to propose a partial model based on incomplete data, each team receives a "visitor scientist" from another team, this implying an informal scientific communication event. This process is performed several times, engaging a discussion in each team and getting a final consensus model created by the whole class. Correct answer is not given to the students, even at the end of the activity, to keep the activity under the parameters of real scientific experience, where there is not a "correct answer" to compare. Instead of this, and following the IBSE standards, a reflection on the process is proposed to students. The lack of complete information and the need to collaborate are part of classroom dynamics focused to the understanding of the process of creation of the scientific knowledge. This activity is part of the C3 Project on Creation of Scientific Knowledge that is being applied in the school.

  10. Effects of music and art education in early life and oral functions on the QOL of the Takarazuka Revue Company OG compared with general elderly females.

    PubMed

    Masutani, Takiko; Yamamoto, Yasuji; Konishi, Junya; Maeda, Kiyoshi

    2010-03-01

    Today, Japan is becoming a super-aged society, with senior citizens already constituting over 21% of the population. In this situation, the question of how elderly people can extend their lives and enjoy independent lifestyles is becoming more important. The present study aims to clarify the relationship between the Quality of Life (QOL) of elderly females and their current oral functions and experiences of music and art education in early life. We carried out a survey study focusing on elderly females (Takarazuka Revue Company OG group and general female group) by carrying out a questionnaire survey and comparing cognitive function, oral examinations, cerebral atrophy in magnetic resonance imaging, and other characteristics. It was shown that the Takarazuka Revue Company OG group had greater hippocampal volumes and significantly higher cognitive functions than the general female group. In addition, in the general female group, there was a significant correlation between a decrease in the number of remaining teeth and a decrease in activities in daily living, but in the Takarazuka Revue Company OG group, no such correlation was observed. The results showed that those who have received art education as part of their careers over an extensive period since early life have higher levels of cognitive function, QOL, physical activity, social activity and life satisfaction compared with the general female group; showing that they sense a purpose in life and live with a positive attitude. In contrast, in the general female group, those who have continued to enjoy hobbies have higher levels of cognitive function, QOL, physical activity, social activity and life satisfaction than those who have not, thus showing that they live with a positive attitude.

  11. The Directed Reading-Thinking Activity (DR-TA) and the Traditional Approach Using Tales of Virtue Based on His Majesty the King's Teaching Concepts in Seventh Grade Students' Reading Comprehension

    ERIC Educational Resources Information Center

    Chaemsai, Rungruedee; Rattanavich, Saowalak

    2016-01-01

    This study compares the English reading comprehension and ethical awareness of 7th grade students, when using either a directed reading-thinking activity (DR-TA), or a more traditional approach, involving tales of virtue based on His Majesty the King's teaching concepts. A randomized control group pretest-posttest design was used for the study,…

  12. Induction of Xa10-like Genes in Rice Cultivar Nipponbare Confers Disease Resistance to Rice Bacterial Blight.

    PubMed

    Wang, Jun; Tian, Dongsheng; Gu, Keyu; Yang, Xiaobei; Wang, Lanlan; Zeng, Xuan; Yin, Zhongchao

    2017-06-01

    Bacterial blight of rice, caused by Xanthomonas oryzae pv. oryzae, is one of the most destructive bacterial diseases throughout the major rice-growing regions in the world. The rice disease resistance (R) gene Xa10 confers race-specific disease resistance to X. oryzae pv. oryzae strains that deliver the corresponding transcription activator-like (TAL) effector AvrXa10. Upon bacterial infection, AvrXa10 binds specifically to the effector binding element in the promoter of the R gene and activates its expression. Xa10 encodes an executor R protein that triggers hypersensitive response and activates disease resistance. 'Nipponbare' rice carries two Xa10-like genes in its genome, of which one is the susceptible allele of the Xa23 gene, a Xa10-like TAL effector-dependent executor R gene isolated recently from 'CBB23' rice. However, the function of the two Xa10-like genes in disease resistance to X. oryzae pv. oryzae strains has not been investigated. Here, we designated the two Xa10-like genes as Xa10-Ni and Xa23-Ni and characterized their function for disease resistance to rice bacterial blight. Both Xa10-Ni and Xa23-Ni provided disease resistance to X. oryzae pv. oryzae strains that deliver the matching artificially designed TAL effectors (dTALE). Transgenic rice plants containing Xa10-Ni and Xa23-Ni under the Xa10 promoter provided specific disease resistance to X. oryzae pv. oryzae strains that deliver AvrXa10. Xa10-Ni and Xa23-Ni knock-out mutants abolished dTALE-dependent disease resistance to X. oryzae pv. oryzae. Heterologous expression of Xa10-Ni and Xa23-Ni in Nicotiana benthamiana triggered cell death. The 19-amino-acid residues at the N-terminal regions of XA10 or XA10-Ni are dispensable for their function in inducing cell death in N. benthamiana and the C-terminal regions of XA10, XA10-Ni, and XA23-Ni are interchangeable among each other without affecting their function. Like XA10, both XA10-Ni and XA23-Ni locate to the endoplasmic reticulum (ER) membrane

  13. The influence of regional geological settings on the seismic hazard level in copper mines in the Legnica-Głogów Copper Belt Area (Poland)

    NASA Astrophysics Data System (ADS)

    Burtan, Zbigniew

    2017-11-01

    The current level of rockburst hazard in copper mines of the (LGOM) Legnica- Głogów Copper Belt Area is mostly the consequence of mining-induced seismicity, whilst the majority of rockbursting events registered to date were caused by high-energy tremors. The analysis of seismic readings in recent years reveals that the highest seismic activity among the copper mines in the LGOM is registered in the mine Rudna. This study investigates the seismic activity in the rock strata in the Rudna mine fields over the years 2006-2015. Of particular interest are the key seismicity parameters: the number of registered seismic events, the total energy emissions, the energy index. It appears that varied seismic activity in the area may be the function of several variables: effective mining thickness, the thickness of burst-prone strata and tectonic intensity. The results support and corroborate the view that principal factors influencing the actual seismic hazard level are regional geological conditions in the copper mines within the Legnica-Głogów Copper Belt Area.

  14. [Ludwig II of Bavaria - the "fairy tale king": his last years from a psychiatric point of view].

    PubMed

    V Zerssen, D

    2010-11-01

    Ludwig II of Bavaria (Germany) entered the political stage at the age of 18, following the premature death of his father Maximilian II in 1864. At that time, Ludwig was a very handsome, slender young man; he was enthusiastic and had a pronounced taste for fine arts and music, and was admired by the people as a "fairy tale king". However, already during the first years of his reign, he displayed traits that fulfilled the ICD-10 criteria for schizotypal disorder together with a combined cluster B personality disorder. They became even more pronounced over time. Towards the end of his life, Ludwig developed "imperial madness", a typical pattern of behavioural excesses including craving for power, splendour, construction, unrestrained spending, excessive eating and sexual exploitation, revenge with a tendency for cruelty, and an inclination for theatrical and sometimes irrational acts. This complex syndrome is usually manifested in excessively egocentric rulers who have almost unlimited power or, in the case of Ludwig II, an overwhelming desire to possess it. His imperial madness was possibly contributed to by an orbitofrontal brain syndrome. One conjecture is that this condition reflected a neurodegenerative process; another is that a primary deficit, initiated by brain damage following a severe bout of meningitis during Ludwig's babyhood, played a role. In this case, functional compensation by other brain areas may have eventually been counteracted by chronic substance abuse in his thirties. The monarch's life ended tragically when he was 40 by which time he had become adipose and had lost most of his teeth; meanwhile, he was placed under tutelage, dismissed and detained. Before his death by drowning in Lake Starnberg (suicide? attempted escape??), Ludwig apparently killed his psychiatrist, Bernhard von Gudden, who carelessly served as his sole attendant. Yet Ludwig's image as the beautiful fairy tale king is still alive in the hearts of successive generations of

  15. Preliminary results from 2017 OGS Explora cruise to the Ross Sea continental slope

    NASA Astrophysics Data System (ADS)

    Rebesco, Michele; De Santis, Laura; Gales, Jenny; Kim, Sookwan; Liu, Yanguang; Sauli, Chiara; Cuffaro, Marco; Bergamasco, Andrea; Colleoni, Florence; Kovacevic, Vedrana; Olivo, Elisabetta; Florindo-Lopez, Cristian; Codiglia, Riccardo; Zgur, Fabrizio; Accettella, Daniela; Gordini, Emiliano; Visnovic, Paolo; Tomini, Isabella; Mansutti, Paolo; Sterzai, Paolo

    2017-04-01

    OGS Explora is back to Antarctica for three projects focused on the Ross Sea eastern continental slope: EU/FP7-EUROFLEETS (http://www.eurofleets.eu) ANTSSS, PNRA (Programma Nazionale Di Ricerche in Antartide) ODYSSEA, and PNRA WHISPERS. These projects employ three main methods: 1) geophysics (multichannel seismic reflection, sub-bottom and multibeam morphobathymetric survey); 2) geology (gravity corer and box-corer); oceanography (CTD, LADCP, turbulence). The general objective is to contribute to the understanding of past and present ocean dynamics and glacial history of this Antarctic sector. In particular, to find evidence (in the geometry and distribution of the stratigraphic sequences) of Miocene-Pleistocene West Antarctic Ice Sheet and East Antarctic Ice Sheet advances and retreats and of their effects on Ross Sea Bottom Water formation and dynamics. The gravity cores provide the chronological control for the Quaternary. Deep sea drilling (through IODP Exp. 374, whose additional alternative sites are surveyed during this cruise) will provide the chronological control for the pre-Quaternary seismic sequences.

  16. GPU-based optical propagation simulator of a laser-processed crystal block for the X'tal cube PET detector.

    PubMed

    Ogata, Yuma; Ohnishi, Takashi; Moriya, Takahiro; Inadama, Naoko; Nishikido, Fumihiko; Yoshida, Eiji; Murayama, Hideo; Yamaya, Taiga; Haneishi, Hideaki

    2014-01-01

    The X'tal cube is a next-generation DOI detector for PET that we are developing to offer higher resolution and higher sensitivity than is available with present detectors. It is constructed from a cubic monolithic scintillation crystal and silicon photomultipliers which are coupled on various positions of the six surfaces of the cube. A laser-processing technique is applied to produce 3D optical boundaries composed of micro-cracks inside the monolithic scintillator crystal. The current configuration is based on an empirical trial of a laser-processed boundary. There is room to improve the spatial resolution by optimizing the setting of the laser-processed boundary. In fact, the laser-processing technique has high freedom in setting the parameters of the boundary such as size, pitch, and angle. Computer simulation can effectively optimize such parameters. In this study, to design optical characteristics properly for the laser-processed crystal, we developed a Monte Carlo simulator which can model arbitrary arrangements of laser-processed optical boundaries (LPBs). The optical characteristics of the LPBs were measured by use of a setup with a laser and a photo-diode, and then modeled in the simulator. The accuracy of the simulator was confirmed by comparison of position histograms obtained from the simulation and from experiments with a prototype detector composed of a cubic LYSO monolithic crystal with 6 × 6 × 6 segments and multi-pixel photon counters. Furthermore, the simulator was accelerated by parallel computing with general-purpose computing on a graphics processing unit. The calculation speed was about 400 times faster than that with a CPU.

  17. The effects of detergents DDM and beta-OG on the singlet excited state lifetime of the chlorophyll a in cytochrome b6f complex from spinach chloroplasts.

    PubMed

    Chen, XiaoBo; Zhao, XiaoHui; Zhang, JianPing; Li, LiangBi; Kuang, TingYun

    2007-08-01

    The singlet excited state lifetime of the chlorophyll a (Chl a) in cytochrome b(6)f (Cyt b(6)f) complex was reported to be shorter than that of free Chl a in methanol, but the value was different for Cyt b(6)f complexes from different sources ( approximately 200 and approximately 600 ps are the two measured results). The present study demonstrated that the singlet excited state lifetime is associated with the detergents n-dodecyl-beta-D-maltoside (DDM) and n-octyl-beta-D-glucopyranoside (beta-OG), but has nothing to do with the different sources of Cyt b(6)f complexes. Compared with the Cyt b(6)f dissolved in beta-OG, the Cyt b(6)f in DDM had a lower fluorescence yield, a lower photodegradation rate of Chl a, and a shorter lifetime of Chl a excited state. In short, the singlet excited state lifetime, approximately 200 ps, of the Chl a in Cyt b(6)f complex in DDM is closer to the true in vivo.

  18. Unexpected findings and promoting monocausal claims, a cautionary tale.

    PubMed

    Copeland, Samantha Marie

    2017-10-01

    Stories of serendipitous discoveries in medicine incorrectly imply that the path from an unexpected observation to major discovery is straightforward or guaranteed. In this paper, I examine a case from the field of research about chronic fatigue syndrome (CFS). In Norway, an unexpected positive result during clinical care has led to the development of a research programme into the potential for the immunosuppressant drug rituximab to relieve the symptoms of CFS. The media and public have taken up researchers' speculations that their research results indicate a causal mechanism for CFS - consequently, patients now have great hope that 'the cause' of CFS has been found, and thus, a cure is sure to follow. I argue that a monocausal claim cannot be correctly asserted, either on the basis of the single case of an unexpected, although positive, result or on the basis of the empirical research that has followed up on that result. Further, assertion and promotion of this claim will have specific harmful effects: it threatens to inappropriately narrow the scope of research on CFS, might misdirect research altogether, and could directly and indirectly harm patients. Therefore, the CFS case presents a cautionary tale, illustrating the risks involved in drawing a theoretical hypothesis from an unexpected observation. Further, I draw attention to the tendency in contemporary clinical research with CFS to promote new research directions on the basis of reductive causal models of that syndrome. Particularly, in the case of CFS research, underdetermination and causal complexity undermine the potential value of a monocausal claim. In sum, when an unexpected finding occurs in clinical practice or medical research, the value of following up on that finding is to be found not in the projected value of a singular causal relationship inferred from the finding but rather in the process of research that follows. © 2016 John Wiley & Sons, Ltd.

  19. Story-telling, women's authority and the "Old Wife's Tale": "The Story of the Bottle of Medicine".

    PubMed

    Abrams, Lynn

    2012-01-01

    The focus of this article is a single personal narrative – a Shetland woman's telling of a story about two girls on a journey to fetch a cure for a sick relative from a wise woman. The story is treated as a cultural document which offers the historian a conduit to a past that is respectful of indigenous woman-centred interpretations of how that past was experienced and understood. The "story of the bottle of medicine" is more than a skilful telling of a local tale; it is a memory practice that provides a path to a deeper and more nuanced understanding of a culture. Applying perspectives from anthropology, oral history and narrative analysis, three sets of questions are addressed: the issue of authenticity; the significance of the narrative structure and storytelling strategies employed; and the nature of the female performance. Ultimately the article asks what this story can tell us about women's interpretation of their own history.

  20. Conceptual frameworks, geomorphic interpretation and storytelling: Tales from Lockyer Creek , Australia.

    NASA Astrophysics Data System (ADS)

    Croke, Jacky; Phillips, Jonathan; Van Dyke, Chris

    2017-04-01

    Earth science knowledge and insight begins with case studies, and theories should be derived from and ultimately evaluated against empirical, case study evidence. However, isolated case studies not linked conceptually to other locations or embedded within a broader framework are often of limited use beyond the study site. Geomorphic evidence and phenomena may be interpreted using a variety of conceptual frameworks (theories, models, laws, methodologies, etc.). The evidence may be, or at least appear to be, consistent with multiple frameworks, even when those constructs are derived from entirely different assumptions or frames of reference. Thus different interpretations and stories can be derived from the same evidence. Our purpose here is to illustrate this phenomenon via a case study from Lockyer Creek, southeast Queensland, Australia. Lockyer Creek is fast becoming one of Australia's most studied catchments with a wealth of data emerging following two extreme flood events in 2011 and 2013. Whilst the initial objective of the Big Flood project was to provide information on the frequency and magnitude of these extreme events, in essence the project revealed a rich 'story' of river evolution and adjustment which at first glance did not appear to 'fit' many established conceptual frameworks and theories. This presentation tells the tale of Lockyer Creek as it relates to selected key conceptual frameworks and importantly how this information can then be used for more effective catchment and flood management.

  1. High Voltage TAL Performance

    NASA Technical Reports Server (NTRS)

    Jacobson, David T.; Jankovsky, Robert S.; Rawlin, Vincent K.; Manzella, David H.

    2001-01-01

    The performance of a two-stage, anode layer Hall thruster was evaluated. Experiments were conducted in single and two-stage configurations. In single-stage configuration, the thruster was operated with discharge voltages ranging from 300 to 1700 V. Discharge specific impulses ranged from 1630 to 4140 sec. Thruster investigations were conducted with input power ranging from 1 to 8.7 kW, corresponding to power throttling of nearly 9: 1. An extensive two-stage performance map was generated. Data taken with total voltage (sum of discharge and accelerating voltage) constant revealed a decrease in thruster efficiency as the discharge voltage was increased. Anode specific impulse values were comparable in the single and two-stage configurations showing no strong advantage for two-stage operation.

  2. Physical Characteristics of Asteroid-like Comet Nucleus C/2001 OG108 (LONEOS)

    NASA Technical Reports Server (NTRS)

    Abell, P. A.; Fernandez, Y. R.; Pravec, P.; French, L. M.; Farnham, T. L.; Gaffey, M. J.; Hardersen, P. S.; Kusnirak, P.; Sarounova, L.; Sheppard, S. S.

    2003-01-01

    For many years several investigators have suggested that some portion of the near-Earth asteroid population may actually be extinct cometary nuclei. Evidence used to support these hypotheses was based on: observations of asteroid orbits and associated meteor showers (e.g. 3200 Phaethon and the Geminid meteor shower); low activity of short period comet nuclei, which implied nonvolatile surface crusts (e.g. Neujmin 1, Arend-Rigaux); and detections of transient cometary activity in some near-Earth asteroids (e.g. 4015 Wilson-Harrington). Recent investigations have suggested that approximately 5-10% of the near- Earth asteroid population may be extinct comets. However if members of the near-Earth asteroid population are extinct cometary nuclei, then there should be some objects within this population that are near their final stages of evolution and so should demonstrate only low levels of activity. The recent detections of coma from near-Earth object 2001 OG108 have renewed interest in this possible comet-asteroid connection. This paper presents the first high quality ground-based near-infrared reflectance spectrum of a comet nucleus combined with detailed lightcurve and albedo measurements.

  3. Evolución de planetas gigantes y posibilidades de su detección directa

    NASA Astrophysics Data System (ADS)

    Brunini, A.; Benvenuto, O. G.

    Desde la reciente detección de planetas gigantes orbitando estrellas cercanas de tipo solar por medio de efecto Doppler, uno de los principales problemas, en cuanto al estudio de los sistemas planetarios extrasolares, se refiere a la posibilidad de obtener evidencia directa de su existencia. Esto parece ser factible gracias a que en un futuro cercano entrarán en operación algunos telescopios especialmente adecuados a estos propósitos. Por tal motivo, hemos comenzado desde hace un tiempo un esfuerzo en cuanto al estudio de la evolución planetaria. A tales efectos hemos adaptado el código de evolución estelar de nuestro Observatorio al caso planetario. Las principales diferencias entre el caso estelar y el planetario se encuentran en la ecuación de estado. A tales fines hemos incluído la reciente ecuación de estado de Saumon, Chabrier y Van Horn, las opacidades radiativas de Guillot et al., procesos de quema de Deuterio, etc. También se ha considerado la posible existencia de fases de hielo y roca en el interior planetario. Por el momento hemos despreciado los efectos de la rotación planetaria. Con este código hemos computado la evolución de planetas con masas desde 10 hasta 0.3 masas de Júpiter. Utilizando nuestros resultados numéricos discutimos la detectabilidad de estos objetos en condiciones realistas.

  4. Characterization of the human oncogene SCL/TAL1 interrupting locus (Stil) mediated Sonic hedgehog (Shh) signaling transduction in proliferating mammalian dopaminergic neurons

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

    Sun, Lei; Department of Physiology, Nankai University School of Medicine, Tianjin 300071; Carr, Aprell L.

    2014-07-11

    Highlights: • Stil is a human oncogene that is conserved in vertebrate species. • Stil functions in the Shh pathway in mammalian cells. • The expression of Stil is required for mammalian dopaminergic cell proliferation. - Abstract: The human oncogene SCL/TAL1 interrupting locus (Stil) is highly conserved in all vertebrate species. In humans, the expression of Stil is involved in cancer cell survival, apoptosis and proliferation. In this research, we investigated the roles of Stil expression in cell proliferation of mammalian dopaminergic (DA) PC12 cells. Stil functions through the Sonic hedgehog (Shh) signal transduction pathway. Co-immunoprecipitation tests revealed that STILmore » interacts with Shh downstream components, which include SUFU and GLI1. By examining the expression of Stil, Gli1, CyclinD2 (cell-cycle marker) and PCNA (proliferating cell nuclear antigen), we found that up-regulation of Stil expression (transfection with overexpression plasmids) increased Shh signaling transduction and PC12 cell proliferation, whereas down-regulation of Stil expression (by shRNA) inhibited Shh signaling transduction, and thereby decreased PC12 cell proliferation. Transient transfection of PC12 cells with Stil knockdown or overexpression plasmids did not affect PC12 cell neural differentiation, further indicating the specific roles of Stil in cell proliferation. The results from this research suggest that Stil may serve as a bio-marker for neurological diseases involved in DA neurons, such as Parkinson’s disease.« less

  5. Report on the Selection Procedure Based on Readers' Responses to the Original Nine Tales in Turkey. Fairytale: An Interdisciplinary Turco-Danish Study of the Collective v. the Individual Nature of the Response to Literature. Report No. 9. Revised.

    ERIC Educational Resources Information Center

    Doltas, Dilek, Ed.; And Others

    Prepared as part of the Turko-Danish Fairytale Project conducted to uncover universal, cross-cultural features in readers' response to literature, this paper reports on a pilot study to determine which three out of nine preselected fairy tales would elicit the most faceted response from a population of Turkish readers. After explaining the…

  6. Intoxications aigues aux organophosphores chez la femme enceinte

    PubMed Central

    Barhoumi, Mohamed Hafed; Bannour, Badra; Barhoumi, Tarek; Jouini, Rami; Marwene, Nadia; Fatnassi, Mohamed Ridha

    2016-01-01

    Les intoxications aiguës par les pesticides organophosphorés (OP) au cours de la grossesse sont des événements rares, peu décrites dans la littérature. A travers cette étude rétrospective, nous rapportons les résultats de sept cas d’ingestion suicidaire d’OP chez des femmes enceintes. Cette intoxication était le plus souvent grave. En effet, cinq des sept parturientes avaient un Glasgow initial < 9 et le POP score était ≥ 3 chez toutes les parturientes. Cinq patientes avaient nécessité une ventilation mécanique de durée moyenne de 3,4 jours. L’évolution était favorable pour toutes les patientes mais dans plus de la moitié des cas elle était défavorable pour le fœtus (mort fœtal in utéro). Deux mécanismes peuvent expliquer ces complications fœtales. Le premier est l’hypoxie fœtale associée ou non à un état de choc qui peuvent se traduire au niveau du RCF par une tachycardie ou des décélérations et aboutir ainsi à un décès in utero. Le deuxième mécanisme est le passage de ces pesticides à travers la barrière placentaire, ce qui pose un risque potentiel pour le fœtus par altération des systèmes enzymatiques des microsomes. PMID:28293343

  7. Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951.

    PubMed

    Cavé, Hélène; Suciu, Stefan; Preudhomme, Claude; Poppe, Bruce; Robert, Alain; Uyttebroeck, Anne; Malet, Michèle; Boutard, Patrick; Benoit, Yves; Mauvieux, Laurent; Lutz, Patrick; Méchinaud, Françoise; Grardel, Nathalie; Mazingue, Francoise; Dupont, Madeleine; Margueritte, Geneviève; Pages, Marie-Pierre; Bertrand, Yves; Plouvier, Emmanuel; Brunie, Ghislaine; Bastard, Christian; Plantaz, Dominique; Vande Velde, Isabel; Hagemeijer, Anne; Speleman, Frank; Lessard, Michel; Otten, Jacques; Vilmer, Etienne; Dastugue, Nicole

    2004-01-15

    In a series of 153 children with T-cell malignancies enrolled in 2 consecutive European Organization for Research and Treatment of Cancer (EORTC) trials, we assessed the HOX11L2 expression and/or the presence of a t(5;14)(q35;q32). Additionally, in 138 of these patients, HOX11 expression and SIL-TAL rearrangement were also assessed. These alterations were mutually exclusive, and their frequency was 23% (n = 35), 7% (n = 10), and 12% (n = 17), respectively. HOX11L2/t(5;14) positivity was more frequent in acute lymphoblastic leukemia (ALL) with cortical T immunophenotype and in children aged between 6 and 9 years. In contrast with previously reported data, patients positive and negative for HOX11L2/t(5;14) were comparable with regard to clinical outcome as well as to the response to a 7-day prephase treatment or to residual disease at completion of induction therapy. The 3-year event-free survival (EFS) rate (+/- SE percentage) for patients positive and negative for HOX11L2/t(5;14) was 75.5% (+/- 8.1%) and 68.3% (+/- 5.0%), respectively; the hazard ratio was 0.84 (95% confidence interval, 0.40-1.80). Patients with HOX11-high expression and those with SIL-TAL fusion had low levels of residual disease at the end of induction and a favorable prognosis: the 3-year EFS rate was 83.3% (+/- 8.5%) and 75.3% (+/- 12.6%), respectively. The results obtained in HOX11L2/t(5;14) patients in this study do not confirm the unfavorable prognosis reported in previous studies.

  8. Macrosomie fœtale à Lubumbashi: facteurs de risque et pronostic maternel et périnatal

    PubMed Central

    Luhete, Prosper Kakudji; Mukuku, Olivier; Kiopin, Patrick Mubinda; Tambwe, Albert Mwembo; Kayamba, Prosper Kalenga Muenze

    2016-01-01

    Introduction La macrosomie fœtale est habituellement définie par un poids de naissance supérieur ou égal à 4000 grammes. L'objectif de cette étude est de déterminer la fréquence de la macrosomie, d'identifier les facteurs étiologiques et d’évaluer le pronostic maternel et périnatal. Méthodes Il s'agit d'une étude cas-témoins menéeau sein des maternités de 10 hôpitaux généraux de référence de la ville de Lubumbashi en République Démocratique du Congoentre le 1er décembre 2013 et le 31 mars 2014. Les accouchées ont été réparties en deux groupes, en fonction du poids de naissance de leurs nouveau-nés: groupe I (≥4000 grammes ou plus) et groupe II (2500 à 3500 grammes). Les caractéristiques maternelles, l'environnement obstétrical ainsi que le pronostic maternel et périnatal ont été étudiés et comparés dans les deux groupes. Les données ont été analysées à l'aide du logiciel Épi info version 7.1. Les différences étaient jugées significatives pour un seuil de p<0,05. Résultats Au total, 668 mères et leurs nouveau-nés ont été inclus dont 167 macrosomes et 501témoins. L'incidence de la macrosomie fœtale était de 5,7%. Comparativement aux mères de témoins, nous avons trouvé que les mères des nouveau-nés macrosomes étaient plus âgées, multipares, multigestes, obèses, diabétiques et avaient antérieurement donné naissance à un macrosome. Les taux de césarienne et de délivrance pathologique étaient significativement élevés chez les mères de macrosomes que chez celles de témoins. Lesexe masculin était significativement plus prédominant chez macrosomes que chez les témoins. La dystocie des épaules étaitenregistrée uniquement dans le groupe des macrosomes. Conclusion La prévalence de l'accouchement d'un macrosome à Lubumbashi est de 5,7%. La macrosomie est souvent à l'origine de complications maternelles et périnatales. La réduction de ces dernières passe par une meilleure connaissance des

  9. Efficient Type Representation in TAL

    NASA Technical Reports Server (NTRS)

    Chen, Juan

    2009-01-01

    Certifying compilers generate proofs for low-level code that guarantee safety properties of the code. Type information is an essential part of safety proofs. But the size of type information remains a concern for certifying compilers in practice. This paper demonstrates type representation techniques in a large-scale compiler that achieves both concise type information and efficient type checking. In our 200,000-line certifying compiler, the size of type information is about 36% of the size of pure code and data for our benchmarks, the best result to the best of our knowledge. The type checking time is about 2% of the compilation time.

  10. Metal abundance of Tal 13

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

    Zinn, R.; Diaz, A.I.

    1982-08-01

    Low-resolution spectrograms have been obtained of the three RR Lyrae variables in the distant and very sparse globular cluster Pal 13. A comparison of these spectrograms with similar ones of several RR Lyrae variables in the globular clusters M4, M5, and M22 reveals that Pal 13 is intermediate to M5 and M22 in metal abundance. A value of (Fe/H) = -1.67 +- 0.15 is obtained for Pal 13 by adopting Zinn's (1980a (Astrophys. J. Suppl. 42,19)) values of (Fe/H) for these other clusters. Pal 13 is another example of a distant halo object that is not extremely metal poor.

  11. High Voltage TAL Erosion Characterization

    NASA Technical Reports Server (NTRS)

    Jacobson, David T.

    2003-01-01

    Extended operation of a D-80 anode layer thruster at high voltage was investigated. The thruster was operated for 1200 hours at 700 Volts and 4 Amperes. Laser profilometry was employed to quantify the erosion of the thruster's graphite guard rings and electrodes at 0, 300, 600, 900, and 1200 hours. Thruster performance and electrical characteristics were monitored over the duration of the investigation. The guard rings exhibited asymmetric erosion that was greatest in the region of the cathode. Erosion of the guard rings exposed the magnet poles between 600 to 900 hours of operation.

  12. [Using fairy tales and narrative strategies with the help of a sandpit with children suffering from conduct disorders].

    PubMed

    Konz, M

    2006-01-01

    Our research, focussed on art therapy with primary school children, guided us to the footsteps of women pioneers in the research about children's psyche, like Anna Freud, Melanie Klein, Margaret Loewenfeld, Dora Kalff. We have been inspired by their very personal but nevertheless somehow similar type of research, to work with the children in a blue sand pit, where they could construct and play their personal fairy tales. Thus they share with us their momentary preoccupations, without being forced to talk about them. They are revealing their internal structures, and are integrating, by narration and projection on those figurines in action, their deficient defense mechanisms as well as their negative tendencies. Based on this approach, we expect that there will by an amelioration of their social skills, an enhancement of their intrinsic motivation, and a diminution of their conduct disorders. The analyze will be done by questionnaires and rating scales constructed especially for this research, as well as by sociograms, with the help of descriptive non parametric statistics.

  13. Towards multifunctional agricultural landscapes in Europe: Assessing and governing synergies between food production, biodiversity, and ecosystem services - TALE

    NASA Astrophysics Data System (ADS)

    Volk, Martin; Cord, Anna; Demiguel, Ángel; Holzkämper, Annelie; Kaim, Andrea; Kirchner, Mathias; Lienhoop, Nele; Nieto Romero, Marta; Nitsch, Heike; Rutz, Cordula; Saa, Antonio; Schmid, Erwin; Schönhart, Martin; Schramek, Jörg; Strauch, Michael; Tarquis Alfonso, Ana Maria; van der Zanden, Emma H.; Verburg, Peter; Willaarts, Bárbara; Zarrineh, Nina; Rivas, David; Hagemann, Nina

    2016-04-01

    There is a need to improve our understanding of the synergies between biodiversity, food and energy production and other regulating or cultural ecosystem services (ESS) and the development of technical and policy measures to support these synergies. Procedures to quantify synergies and trade-offs between ESS and biodiversity are considered as promising solutions to close this gap. The BiodivERsA project TALE aims at developing such methodologies in a set of representative European agricultural landscapes in Germany, Switzerland, Austria, The Netherlands and Spain. This will be done by using i) a framework that links process-based, integrated, and statistical models with optimization algorithms, and ii) a set of land use scenarios and land use policies, iii) a systematic stakeholder integration process that allows the incorporation of expert knowledge in all phases of the research project to safeguard that research results are of practical relevance. Moreover, the project not only addresses experts but provides an innovative online learning environment that is accessible also for students and the general public.

  14. Evidence for regulation of columnar habit in apple by a putative 2OG-Fe(II) oxygenase.

    PubMed

    Wolters, Pieter J; Schouten, Henk J; Velasco, Riccardo; Si-Ammour, Azeddine; Baldi, Paolo

    2013-12-01

    Understanding the genetic mechanisms controlling columnar-type growth in the apple mutant 'Wijcik' will provide insights on how tree architecture and growth are regulated in fruit trees. In apple, columnar-type growth is controlled by a single major gene at the Columnar (Co) locus. By comparing the genomic sequence of the Co region of 'Wijcik' with its wild-type 'McIntosh', a novel non-coding DNA element of 1956 bp specific to Pyreae was found to be inserted in an intergenic region of 'Wijcik'. Expression analysis of selected genes located in the vicinity of the insertion revealed the upregulation of the MdCo31 gene encoding a putative 2OG-Fe(II) oxygenase in axillary buds of 'Wijcik'. Constitutive expression of MdCo31 in Arabidopsis thaliana resulted in compact plants with shortened floral internodes, a phenotype reminiscent of the one observed in columnar apple trees. We conclude that MdCo31 is a strong candidate gene for the control of columnar growth in 'Wijcik'. No claim to original European Union works. New Phytologist © 2013 New Phytologist Trust.

  15. The two-component system GrvRS (EtaRS) regulates ace expression in Enterococcus faecalis OG1RF.

    PubMed

    Roh, Jung Hyeob; Singh, Kavindra V; La Rosa, Sabina Leanti; Cohen, Ana Luisa V; Murray, Barbara E

    2015-01-01

    Expression of ace (adhesin to collagen of Enterococcus faecalis), encoding a virulence factor in endocarditis and urinary tract infection models, has been shown to increase under certain conditions, such as in the presence of serum, bile salts, urine, and collagen and at 46 °C. However, the mechanism of ace/Ace regulation under different conditions is still unknown. In this study, we identified a two-component regulatory system GrvRS as the main regulator of ace expression under these stress conditions. Using Northern hybridization and β-galactosidase assays of an ace promoter-lacZ fusion, we found transcription of ace to be virtually absent in a grvR deletion mutant under the conditions that increase ace expression in wild-type OG1RF and in the complemented strain. Moreover, a grvR mutant revealed decreased collagen binding and biofilm formation as well as attenuation in a murine urinary tract infection model. Here we show that GrvR plays a major role in control of ace expression and E. faecalis virulence. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Múltiples estados de desorden en el etanol sólido

    NASA Astrophysics Data System (ADS)

    Fernández-Perea, R.

    El diagrama de fases del etanol por debajo de los 169 K será presentado. Se mostrará que el etanol puede solidificarse en tres fases con diversos niveles de desorden,(como un vidrio(G), como un vidrio orientacional (OG) y como un cristal de fase rotora (RP)) además de en una fase totalmente cristalina. Las estructuras de estas tres fases serán presentadas tal y como se deducen a partir de diversas medidas de difracción de neutrones al igual que las proporciones de los isómeros de dicho material en las fases desordenadas y se compararán con los resultados de la fase cristalina y del líquido superenfriado. Igualmente diversas medidas sobre su dinámica serán presentadas, tanto de dispersión de neutrones, como de capacidad calorífica y de medidas dieléctricas y comparadas con modelos teóricos y simulaciones para tratar de explicar los procesos de relajación observados y las transiciones entre las diversas fases.

  17. The TALE Class Homeobox Gene Smed-prep Defines the Anterior Compartment for Head Regeneration

    PubMed Central

    Felix, Daniel A.; Aboobaker, A. Aziz

    2010-01-01

    Planaria continue to blossom as a model system for understanding all aspects of regeneration. They provide an opportunity to understand how the replacement of missing tissues from preexisting adult tissue is orchestrated at the molecular level. When amputated along any plane, planaria are capable of regenerating all missing tissue and rescaling all structures to the new size of the animal. Recently, rapid progress has been made in understanding the developmental pathways that control planarian regeneration. In particular Wnt/beta-catenin signaling is central in promoting posterior fates and inhibiting anterior identity. Currently the mechanisms that actively promote anterior identity remain unknown. Here, Smed-prep, encoding a TALE class homeodomain, is described as the first gene necessary for correct anterior fate and patterning during planarian regeneration. Smed-prep is expressed at high levels in the anterior portion of whole animals, and Smed-prep(RNAi) leads to loss of the whole brain during anterior regeneration, but not during lateral regeneration or homeostasis in intact worms. Expression of markers of different anterior fated cells are greatly reduced or lost in Smed-prep(RNAi) animals. We find that the ectopic anterior structures induced by abrogation of Wnt signaling also require Smed-prep to form. We use double knockdown experiments with the S. mediterranea ortholog of nou-darake (that when knocked down induces ectopic brain formation) to show that Smed-prep defines an anterior fated compartment within which stem cells are permitted to assume brain fate, but is not required directly for this differentiation process. Smed-prep is the first gene clearly implicated as being necessary for promoting anterior fate and the first homeobox gene implicated in establishing positional identity during regeneration. Together our results suggest that Smed-prep is required in stem cell progeny as they form the anterior regenerative blastema and is required for

  18. The TALE class homeobox gene Smed-prep defines the anterior compartment for head regeneration.

    PubMed

    Felix, Daniel A; Aboobaker, A Aziz

    2010-04-22

    Planaria continue to blossom as a model system for understanding all aspects of regeneration. They provide an opportunity to understand how the replacement of missing tissues from preexisting adult tissue is orchestrated at the molecular level. When amputated along any plane, planaria are capable of regenerating all missing tissue and rescaling all structures to the new size of the animal. Recently, rapid progress has been made in understanding the developmental pathways that control planarian regeneration. In particular Wnt/beta-catenin signaling is central in promoting posterior fates and inhibiting anterior identity. Currently the mechanisms that actively promote anterior identity remain unknown. Here, Smed-prep, encoding a TALE class homeodomain, is described as the first gene necessary for correct anterior fate and patterning during planarian regeneration. Smed-prep is expressed at high levels in the anterior portion of whole animals, and Smed-prep(RNAi) leads to loss of the whole brain during anterior regeneration, but not during lateral regeneration or homeostasis in intact worms. Expression of markers of different anterior fated cells are greatly reduced or lost in Smed-prep(RNAi) animals. We find that the ectopic anterior structures induced by abrogation of Wnt signaling also require Smed-prep to form. We use double knockdown experiments with the S. mediterranea ortholog of nou-darake (that when knocked down induces ectopic brain formation) to show that Smed-prep defines an anterior fated compartment within which stem cells are permitted to assume brain fate, but is not required directly for this differentiation process. Smed-prep is the first gene clearly implicated as being necessary for promoting anterior fate and the first homeobox gene implicated in establishing positional identity during regeneration. Together our results suggest that Smed-prep is required in stem cell progeny as they form the anterior regenerative blastema and is required for

  19. Promoter/repressor system of Lactobacillus plantarum phage og1e: characterization of the promoters pR49-pR-pL and overproduction of the cro-like protein cng in Escherichia coli.

    PubMed

    Kakikawa, M; Watanabe, N; Funawatashi, T; Oki, M; Yasukawa, H; Taketo, A; Kodaira, K I

    1998-07-30

    The Lactobacillus plantarum phage og1e (42259bp) has two repressor-like genes cng and cpg oriented oppositely, accompanied by three potential promoters pR, pL and pR49, and seven operator-like sequences (GATAC-boxes) (Kodaira et al., 1997). In this study, the og1e putative promoters were introduced into the Escherichia coli promoter-detecting plasmid pKK232-8. In E. coli CK111, pR (pKPR1), pL (pKPL1) and pR49 (pKPR49) exhibited distinct CAT activities. When pKPR1 or pKPL1 was coexistent with a compatible plasmid pACYC184 carrying pR-cng (pA4PRCN1), the CAT activity was decreased significantly. On the other hand, cng directed a protein (Cng) of 10.1 kDa in E. coli under the control of T7 promoter. Gel mobility-shift assays demonstrated that Cng binds specifically to a DNA region containing the GATAC-boxes. In addition, primer extension analyses demonstrated that the two sequences pR and pL act as a promoter in L. plantarum as well as in E. coli. These results suggested that the potential promoters pR and pL probably function for the lytic and lysogenic pathways, respectively, and Cng may act as a repressor presumably through the GATAC-boxes as operators.

  20. L'endométriose pariétale cicatricielle après césarienne: une entité rare

    PubMed Central

    El Fahssi, Mohammed; Lomdo, Massama; Bounaim, Ahmed; Ali, Abdelmounaim Ait; Sair, Khalid

    2016-01-01

    L'endométriose de la paroi est une entité clinique rare, dont la physiopathologie demeure imprécise. Elle survient le plus souvent après une intervention chirurgicale gynécologique ou obstétricale. Nous rapportons le cas d'une patiente présentant une douleur cyclique, au niveau de la cicatrice de césarienne, Avec à l'examen clinique une masse de 5cm localisée au niveau de la fosse iliaque droite. la tomodensitométrie montre une masse de densité tissulaire de 45mm de grand axe. D'où la décision d'excision large de la lésion dont l’étude anatomopathologique confirme le diagnostic d'endométriose pariétale. Les suites postopératoires étaient simples avec un recul de 20 mois sans récidive de la masse ni de la douleur. A travers notre cas, nous insisterons sur les caractéristiques de cette pathologie, ce qui permettra au praticien de comprendre l'intérêt du diagnostic et de la prise en charge précoce de cette affection ainsi que la possibilité de sa prévention au cours de chaque chirurgie gynécologique ou obstétricale. PMID:27642418

  1. A tale of two California droughts: Lessons amidst record warmth and dryness in a region of complex physical and human geography

    NASA Astrophysics Data System (ADS)

    Swain, Daniel L.

    2015-11-01

    The state of California has experienced the worst drought in its historical record during 2012-2015. Adverse effects of this multiyear event have been far from uniformly distributed across the region, ranging from remarkably mild in most of California's densely populated coastal cities to very severe in more rural, agricultural, and wildfire-prone regions. This duality of impacts has created a tale of two very different California droughts—highlighting enhanced susceptibility to climate stresses at the environmental and socioeconomic margins of California. From a geophysical perspective, the persistence of related atmospheric anomalies has raised a number of questions regarding the drought's origins—including the role of anthropogenic climate change. Recent investigations underscore the importance of understanding the underlying physical causes of extremes in the climate system, and the present California drought represents an excellent case study for such endeavors. Meanwhile, a powerful El Niño event in the Pacific Ocean offers the simultaneous prospect of partial drought relief but also an increased risk of flooding during the 2015-2016 winter—a situation illustrative of the complex hydroclimatic risks California and other regions are likely to face in a warming world.

  2. Public Library YA Program Roundup: Murder, We Wrote...and Played [and] Asleep in the Library: Girl Scouts Earn "From Dreams to Reality" Patch [and] Sign Language Funshop [and] Science Fair Help Day [and] A Skyomish Fairy Tale [and] The POW! Project: Picturing Our World! Teens Create Art and Self-Esteem at the Boston Public Library.

    ERIC Educational Resources Information Center

    Goldsmith, Francisca; Seblonka, Cathy Sullivan; Wagner, Joyce; Smith, Tammy; Sipos, Caryn; Bodart, Joni Richards

    1998-01-01

    Includes six articles that describe public library programs for teens. Highlights include interactive murder mysteries; a girl scout sleepover program on career awareness; sign language workshop; a Science Fair help day that included guest speakers; a unit on fairy tales and legends; and a project to enhance creativity and self-esteem. (LRW)

  3. Influence du traitement ionisant par rayonnement γ sur le pouvoir antioxydant de fractions polyphénoliques issues de substances d'origine végétale

    NASA Astrophysics Data System (ADS)

    Stuyck, S.; Connaulte, J.; Lesgards, G.; Prost, M.; Raffi, J.

    1998-04-01

    Ionizing radiation of vegetables is a cleaning up and preservation physical treatment which consists in submitting them to γ radiation, X radiation or electrons beam. This study deals with the influence of γ radiation on antioxidative effect of vegetables polyphenolic parts. In that purpose, we use a simple biological test based on erythrocytes haemolysis. Le traitement ionisant des produits végétaux est un procédé physique d'assainissement et de conservation qui consiste à les soumettre à l'action de rayonnements γ, de rayons X ou de faisceaux d'électrons. Ce travail porte sur l'étude de l'influence des rayonnements γ sur le pouvoir antioxydant de fractions polyphénoliques issues de substances d'origine végétale. Pour cela, un test biologique basé sur l'hémolyse d'érythrocytes est utilisé.

  4. Population Size, Growth, and Environmental Justice Near Oil and Gas Wells in Colorado.

    PubMed

    McKenzie, Lisa M; Allshouse, William B; Burke, Troy; Blair, Benjamin D; Adgate, John L

    2016-11-01

    We evaluated population size and factors influencing environmental justice near oil and gas (O&G) wells. We mapped nearest O&G well to residential properties to evaluate population size, temporal relationships between housing and O&G development, and 2012 housing market value distributions in three major Colorado O&G basins. We reviewed land use, building, real estate, and state O&G regulations to evaluate distributive and participatory justice. We found that by 2012 at least 378,000 Coloradans lived within 1 mile of an active O&G well, and this population was growing at a faster rate than the overall population. In the Denver Julesburg and San Juan basins, which experienced substantial O&G development prior to 2000, we observed a larger proportion of lower value homes within 500 feet of an O&G well and that most O&G wells predated houses. In the Piceance Basin, which had not experienced substantial prior O&G development, we observed a larger proportion of high value homes within 500 feet of an O&G well and that most houses predated O&G wells. We observed economic, rural, participatory, and/or distributive injustices that could contribute to health risk vulnerabilities in populations near O&G wells. We encourage policy makers to consider measures to reduce these injustices.

  5. Dissolving Borders and Broadening Perspectives through Latino Traditional Literature.

    ERIC Educational Resources Information Center

    Smolen, Lynn Atkinson; Ortiz-Castro, Victoria

    2000-01-01

    Offers a brief historical perspective on Latino folk literature. Discusses 26 recently published books for children and adolescents in both English and Spanish, organized into origin tales, tales based on historical facts, trickster tales, and cumulative tales. Describes activities to use with these books to foster literacy and make powerful…

  6. A novel smart supramolecular organic gelator exhibiting dual-channel responsive sensing behaviours towards fluoride ion via gel-gel states.

    PubMed

    Mehdi, Hassan; Pang, Hongchang; Gong, Weitao; Dhinakaran, Manivannan Kalavathi; Wajahat, Ali; Kuang, Xiaojun; Ning, Guiling

    2016-07-07

    A novel smart supramolecular organic gelator G-16 containing anion and metal-coordination ability has been designed and synthesized. It shows excellent and robust gelation capability as a strong blue fluorescent supramolecular organic gel OG in DMF. Addition of Zn(2+) produced Zn(2+)-coordinated supramolecular metallogel OG-Zn. Organic gel OG and organometallic gel OG-Zn exhibited efficient and different sensing behaviors towards fluoride ion due to the variation in self-assembling nature. Supramolecular metallogel OG-Zn displayed specific selectivity for fluoride ion and formed OG-Zn-F with dramatic color change from blue to blue green in solution and gel to gel states. Furthermore after directly addition of fluoride into OG produced fluoride containing organic gel OG-F with drastically modulation in color from blue to greenish yellow fluorescence via strong aggregation-induced emission (AIE) property. A number of experiments were conducted such as FTIR, (1)H NMR, and UV/Vis spectroscopies, XRD, SEM and rheology. These results revealed that the driving forces involved in self-assembly of OG, OG-Zn, OG-Zn-F and OG-F were hydrogen bonding, metal coordination, π-π interactions, and van der Waal forces. In contrast to the most anion responsive gels, particularly fluoride ion responsive gels showed gel-sol state transition on stimulation by anions, the gel state of OG and OG-Zn did not show any gel-to-sol transition during the whole F(-) response process.

  7. The tale wagged by the DAG: broadening the scope of causal inference and explanation for epidemiology.

    PubMed

    Krieger, Nancy; Davey Smith, George

    2016-12-01

    'Causal inference', in 21st century epidemiology, has notably come to stand for a specific approach, one focused primarily on counterfactual and potential outcome reasoning and using particular representations, such as directed acyclic graphs (DAGs) and Bayesian causal nets. In this essay, we suggest that in epidemiology no one causal approach should drive the questions asked or delimit what counts as useful evidence. Robust causal inference instead comprises a complex narrative, created by scientists appraising, from diverse perspectives, different strands of evidence produced by myriad methods. DAGs can of course be useful, but should not alone wag the causal tale. To make our case, we first address key conceptual issues, after which we offer several concrete examples illustrating how the newly favoured methods, despite their strengths, can also: (i) limit who and what may be deemed a 'cause', thereby narrowing the scope of the field; and (ii) lead to erroneous causal inference, especially if key biological and social assumptions about parameters are poorly conceived, thereby potentially causing harm. As an alternative, we propose that the field of epidemiology consider judicious use of the broad and flexible framework of 'inference to the best explanation', an approach perhaps best developed by Peter Lipton, a philosopher of science who frequently employed epidemiologically relevant examples. This stance requires not only that we be open to being pluralists about both causation and evidence but also that we rise to the challenge of forging explanations that, in Lipton's words, aspire to 'scope, precision, mechanism, unification and simplicity'. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

  8. Tumorigenic and Antiproliferative Properties of the TALE-Transcription Factors MEIS2D and MEIS2A in Neuroblastoma.

    PubMed

    Groß, Anja; Schulz, Catrine; Kolb, Jasmine; Koster, Jan; Wehner, Sibylle; Czaplinski, Sebastian; Khilan, Abdulghani; Rohrer, Hermann; Harter, Patrick N; Klingebiel, Thomas; Langer, Julian D; Geerts, Dirk; Schulte, Dorothea

    2018-04-15

    Neuroblastoma is one of only a few human cancers that can spontaneously regress even after extensive dissemination, a poorly understood phenomenon that occurs in as many as 10% of patients. In this study, we identify the TALE-homeodomain transcription factor MEIS2 as a key contributor to this phenomenon. We identified MEIS2 as a MYCN-independent factor in neuroblastoma and showed that in this setting the alternatively spliced isoforms MEIS2A and MEIS2D exert antagonistic functions. Specifically, expression of MEIS2A was low in aggressive stage 4 neuroblastoma but high in spontaneously regressing stage 4S neuroblastoma. Moderate elevation of MEIS2A expression reduced proliferation of MYCN -amplified human neuroblastoma cells, induced neuronal differentiation and impaired the ability of these cells to form tumors in mice. In contrast, MEIS2A silencing or MEIS2D upregulation enhanced the aggressiveness of the tumor phenotype. Mechanistically, MEIS2A uncoupled a negative feedback loop that restricts accumulation of cellular retinoic acid, an effective agent in neuroblastoma treatment. Overall, our results illuminate the basis for spontaneous regression in neuroblastoma and identify an MEIS2A-specific signaling network as a potential therapeutic target in this common pediatric malignancy. Significance: This study illuminates the basis for spontaneous regressions that can occur in a common pediatric tumor, with implications for the development of new treatment strategies. Cancer Res; 78(8); 1935-47. ©2018 AACR . ©2018 American Association for Cancer Research.

  9. Brothers Grimm. [Lesson Plan].

    ERIC Educational Resources Information Center

    Discovery Communications, Inc., Bethesda, MD.

    Based on Grimm's fairy tales, this lesson plan presents activities designed to help students understand that fairy tales connect them to earlier generations, help them think about present situations, that magic figures prominently in fairy tales, and that fairy tales can inspire readers to create original works of art. The main activity in the…

  10. Rickettsia Phylogenomics: Unwinding the Intricacies of Obligate Intracellular Life

    PubMed Central

    Gillespie, Joseph J.; Williams, Kelly; Shukla, Maulik; Snyder, Eric E.; Nordberg, Eric K.; Ceraul, Shane M.; Dharmanolla, Chitti; Rainey, Daphne; Soneja, Jeetendra; Shallom, Joshua M.; Vishnubhat, Nataraj Dongre; Wattam, Rebecca; Purkayastha, Anjan; Czar, Michael; Crasta, Oswald; Setubal, Joao C.; Azad, Abdu F.; Sobral, Bruno S.

    2008-01-01

    Background Completed genome sequences are rapidly increasing for Rickettsia, obligate intracellular α-proteobacteria responsible for various human diseases, including epidemic typhus and Rocky Mountain spotted fever. In light of phylogeny, the establishment of orthologous groups (OGs) of open reading frames (ORFs) will distinguish the core rickettsial genes and other group specific genes (class 1 OGs or C1OGs) from those distributed indiscriminately throughout the rickettsial tree (class 2 OG or C2OGs). Methodology/Principal Findings We present 1823 representative (no gene duplications) and 259 non-representative (at least one gene duplication) rickettsial OGs. While the highly reductive (∼1.2 MB) Rickettsia genomes range in predicted ORFs from 872 to 1512, a core of 752 OGs was identified, depicting the essential Rickettsia genes. Unsurprisingly, this core lacks many metabolic genes, reflecting the dependence on host resources for growth and survival. Additionally, we bolster our recent reclassification of Rickettsia by identifying OGs that define the AG (ancestral group), TG (typhus group), TRG (transitional group), and SFG (spotted fever group) rickettsiae. OGs for insect-associated species, tick-associated species and species that harbor plasmids were also predicted. Through superimposition of all OGs over robust phylogeny estimation, we discern between C1OGs and C2OGs, the latter depicting genes either decaying from the conserved C1OGs or acquired laterally. Finally, scrutiny of non-representative OGs revealed high levels of split genes versus gene duplications, with both phenomena confounding gene orthology assignment. Interestingly, non-representative OGs, as well as OGs comprised of several gene families typically involved in microbial pathogenicity and/or the acquisition of virulence factors, fall predominantly within C2OG distributions. Conclusion/Significance Collectively, we determined the relative conservation and distribution of 14354 predicted

  11. The pht4;1-3 mutant line contains a loss of function allele in the Fatty Acid Desaturase 7 gene caused by a remnant inactivated selection marker-a cautionary tale.

    PubMed

    Nilsson, Anders K; Andersson, Mats X

    2017-01-01

    A striking and unexpected biochemical phenotype was found in an insertion mutant line in the model plant Arabidopsis thaliana . One of two investigated insertion mutant lines in the gene encoding the phosphate transporter PHT4;1 demonstrated a prominent loss of trienoic fatty acids, whereas the other insertion line was indistinguishable from wild type in this aspect. We demonstrate that the loss of trienoic fatty acids was due to a remnant inactive negative selection marker gene in this particular transposon tagged line, pht4;1-3 . This constitutes a cautionary tale that warns of the importance to confirm the loss of this type of selection markers and the importance of verifying the relationship between a phenotype and genotype by more than one independent mutant line or alternatively genetic complementation.

  12. Comperative studies with Culex pipiens egg rafts. Immunogenetic, electrophoretic and enzymatic analysis of unfertilized, compatible and incompatible fertilized eggs.

    PubMed

    Schumann, W

    1974-01-01

    By applying immunologic, electrophoretic and enzymatic methods, extracts of different raft types of Culex pipiens were analysed. Rafts of the crosses Pa x Pa and Ha x Ha contained four common antigens, while unfertilized rafts of Pa and Ha (no antisera were prepared against them) and rafts of the crosses Og x Og, Og x Pa, and Pa x Og shared three common antigens with the remaining raft extracts. Disk-electrophoresis of raft extracts in acrylamide gel resulted in different electropherograms. Ten protein bands were common to all these raft types. The unfertilized rafts of Pa and Ha yielded three more protein bands, the crosses Pa x Ha and Ha x Pa one more, the crosses Og x Og and Pa x Og three more, and Og x Pa two more. Many enzymes were demonstrated in the raft extracts after they were separated in acrylamide gel and incubated with the corresponding substrate solutions. All the raft types possessed one enzyme type for glutaminate-, lactate-, glucose-6-phosphate-dehydrogenase and catalase. Malate-dehydrogenase and leucine aminopeptidase occurred in each raft type as two isoenzymes. Alkaline phosphatase was observed as a single enzyme, but was lacking in rafts of the crosses Pa X Pa and Ha X Ha. While rafts of the crosses Og x Og and Og x Pa possessed two acid phosphatases, three could be demonstrated for the remaining raft types. Up to eight esterases appeared; rafts of the crosses Og x Og and Og x Pa possessed seven such activities. The results obtained by the Ouchterlony test, disk-electrophoresis and the histochemical enzyme tests are discussed in context and checked according to the phenomenon of incompatibility.

  13. Factors detracting students from applying for an obstetrics and gynecology residency.

    PubMed

    Gariti, Dominique L; Zollinger, Terrell W; Look, Katherine Y

    2005-07-01

    This study compares perception about the characteristics of obstetrics-gynecology (OG) of medical students who choose to pursue a residency in OG and those students who choose to enter another specialty. Fourth-year medical students were asked to complete a survey addressing their perceptions about OG. Responses were compared of (1) those entering OG to those entering other specialties, (2) those entering OG to those who seriously considered entering OG but chose another discipline, and (3) males to females. Chi-square tests were used for the comparisons. Of the 267 eligible students, 137 (51.1%) completed the survey. Clerkship satisfaction was rated as high by 88.9% of students choosing OG vs 10.2% (P<.0005) of those who chose another discipline. The emerging predominance of female providers detracted 38.5% of males vs 10.2% of females (P<.0005). Student perception of an OG clerkship may detract them from pursuing OG as a career.

  14. Evolution of Transcription Activator-Like Effectors in Xanthomonas oryzae

    PubMed Central

    Erkes, Annett; Reschke, Maik; Boch, Jens

    2017-01-01

    Abstract Transcription activator-like effectors (TALEs) are secreted by plant–pathogenic Xanthomonas bacteria into plant cells where they act as transcriptional activators and, hence, are major drivers in reprogramming the plant for the benefit of the pathogen. TALEs possess a highly repetitive DNA-binding domain of typically 34 amino acid (AA) tandem repeats, where AA 12 and 13, termed repeat variable di-residue (RVD), determine target specificity. Different Xanthomonas strains possess different repertoires of TALEs. Here, we study the evolution of TALEs from the level of RVDs determining target specificity down to the level of DNA sequence with focus on rice-pathogenic Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc) strains. We observe that codon pairs coding for individual RVDs are conserved to a similar degree as the flanking repeat sequence. We find strong indications that TALEs may evolve 1) by base substitutions in codon pairs coding for RVDs, 2) by recombination of N-terminal or C-terminal regions of existing TALEs, or 3) by deletion of individual TALE repeats, and we propose possible mechanisms. We find indications that the reassortment of TALE genes in clusters is mediated by an integron-like mechanism in Xoc. We finally study the effect of the presence/absence and evolutionary modifications of TALEs on transcriptional activation of putative target genes in rice, and find that even single RVD swaps may lead to considerable differences in activation. This correlation allowed a refined prediction of TALE targets, which is the crucial step to decipher their virulence activity. PMID:28637323

  15. Tales of sociology and the nursing curriculum: revisiting the debates.

    PubMed

    Aranda, Kay; Law, Kate

    2007-08-01

    . Sociology and the nursing curriculum; editorial. Nurse Education in Practice 4, 81-82; Mowforth, G., Harrison, J., Morris, M., 2005. An investigation into adult nursing students' experience of the relevance and application of behavioural sciences (biology, psychology and sociology) across two different curricula. Nurse Education Today 25, 41-48]. Much attention has been given to the role, utility and value of sociology mostly within pre-registration but also post-registration nursing curricula. Through an initial analysis of a series of letters appearing in The Nursing Times over a 12 week period in 2004, and using an analytical framework of four tales (realist, critical, deconstructive and reflexive) we revisit this relationship. Unlike previous debates our argument is that this relationship is more usefully viewed as emblematic of the legitimation crisis inherent in all modern projects. We argue that in order to move beyond the 'utility' discussion, an interrogation of the knowledge claims of both nursing and sociology is required.

  16. A hydrophobic residue in the TALE homeodomain of PBX1 promotes epithelial-to-mesenchymal transition of gastric carcinoma.

    PubMed

    He, Changyu; Wang, Zhenqiang; Zhang, Li; Yang, Liyun; Li, Jianfang; Chen, Xuehua; Zhang, Jun; Chang, Qing; Yu, Yingyan; Liu, Bingya; Zhu, Zhenggang

    2017-07-18

    Pre-B-cell leukemia homeobox 1 (PBX1) was originally identified as a proto-oncogene in human leukemia. Although this protein has been shown to contribute to cellular development and tumorigenesis, the role of PBX1 in gastric carcinoma (GC) remains unclear. In this study, we observed increased expression of PBX1 in GC tissues compared with adjacent normal tissues. This increase in PBX1 expression levels negatively correlated with HOXB9 mRNA expression and was also associated with malignancy and metastasis. PBX1 promoted proliferation and metastasis of GC cells both in vitro and in vivo.These phenomena were also accompanied by epithelial-to-mesenchymal transition (EMT). Additionally, we observed that PBX1 promotes the expression of tumor growth and angiogenic factors. A structural model of the PBX1-HOX complex revealed that hydrophobic binding between PBX1 and the hexapeptide motif might be required for EMT induction. This analysis also demonstrated that the Phe252 residue in the first helix of the TALE homeodomain is involved in the latter hydrophobic binding reaction. In vitro data from PBX1 mutants suggest that PBX1 cannot promote tumorigenesis of GC cells via EMT induction when Phe252 residues lose hydrophobicity. It is likely that the presence of this residue is essential in facilitating hydrophobic binding with the hexapeptide motif. These findings suggest that PBX1 may be a potential target for GC treatment and this study provides a platform to elucidate the molecular mechanisms that underpin the role of PBX1 in GC tumorigenesis.

  17. Understanding Outdoor Gyms in Public Open Spaces: A Systematic Review and Integrative Synthesis of Qualitative and Quantitative Evidence

    PubMed Central

    Lee, Janet Lok Chun; Lo, Temmy Lee Ting

    2018-01-01

    (1) Background: An outdoor gym (OG) is environmental infrastructure built in a public open space to promote structured physical activity. The provision of OGs is increasingly seen as an important strategy to realize public health agendas promoting habitual physical activity. A systematic review was conducted to synthesize characteristics of OG and OG users’ experiences and perceptions in different cultural contexts; (2) Methods: Online searches of multidisciplinary databases were conducted in health, sport and recreation, and urban planning disciplines. Characteristics of OGs were synthesized by integrating evidence from quantitative, qualitative, and mix-methods studies. The experiences and perceptions of OG users from both qualitative data and survey responses were synthesized through framework analysis; (3) Results: Nine studies met the inclusion criteria (three quantitative studies, four mixed-methods studies, and two pure qualitative studies). None were excluded on the basis of quality. OGs mainly serve adult and older adult population groups. Their size, design, and instructional support vary across studies. The inclusion of functional types of equipment did not have a unified standard. Regarding experiences and perceptions of OGs, five major themes emerged: “health”, “social connectedness”, “affordable”, “support”, and “design and promotion”; (4) Conclusions: The OG characteristics synthesis guides the direction in further studies regarding exploration of design parameters. The qualitative and quantitative synthesis revealed that health was a central theme of users’ experiences. OGs are also spaces where community-dwellers can find social connectedness while participating in structured physical activity at no cost. Findings from this review create knowledge support for OG as environmental infrastructure for further research and facilitate the understanding of users’ experiences and perceptions of OGs in different cultural contexts

  18. FACTORES SOCIO-ESTRUCTURALES Y EL ESTIGMA HACIA EL VIH/SIDA: EXPERIENCIAS DE PUERTORRIQUEÑOS/AS CON VIH/SIDA AL ACCEDER SERVICIOS DE SALUD

    PubMed Central

    RIVERA-DIAZ, MARINILDA; VARAS-DIAZ, NELSON; REYES-ESTRADA, MARCOS; SURO, BEATRIZ; CORIANO, DORALIS

    2013-01-01

    RESUMEN El estigma relacionado al VIH/SIDA continúa afectando la prestación de servicios de salud y el bienestar físico y mental de las personas con VIH/SIDA (PVS). Recientemente la literatura científica ha señalado la importancia de comprender las manifestaciones de estigma más allá de las interacciones individuales. Por tal razón, investigaciones recientes en y fuera de Puerto Rico enfatizan la importancia de entender cómo factores socio-estructurales (FSE) influyen en los procesos de estigmatización social. Con el propósito de examinar los FSE que influyen en las manifestaciones de estigma relacionado al VIH/SIDA, realizamos y analizamos nueve grupos focales compuestos por hombres y mujeres en tratamiento para el VIH/SIDA que habían tenido experiencias estigmatizantes. Los participantes identificaron FSE relacionados a las manifestaciones de estigma, tales como el uso de viviendas especializadas, descentralización de los servicios de salud y el desarrollo de protocolos administrativos excluyentes en los servicios de salud. Los resultados demuestran la importancia de considerar los FSE en el desarrollo e implementación de intervenciones dirigidas a la población. PMID:24639599

  19. Characteristic Features of Kynurenine Aminotransferase Allosterically Regulated by (Alpha)-Ketoglutarate in Cooperation with Kynurenine

    PubMed Central

    Okada, Ken; Angkawidjaja, Clement; Koga, Yuichi; Takano, Kazufumi; Kanaya, Shigenori

    2012-01-01

    Kynurenine aminotransferase from Pyrococcus horikoshii OT3 (PhKAT), which is a homodimeric protein, catalyzes the conversion of kynurenine (KYN) to kynurenic acid (KYNA). We analyzed the transaminase reaction mechanisms of this protein with pyridoxal-5′-phosphate (PLP), KYN and α-ketoglutaric acid (2OG) or oxaloacetic acid (OXA). 2OG significantly inhibited KAT activities in kinetic analyses, suggesting that a KYNA biosynthesis is allosterically regulated by 2OG. Its inhibitions evidently were unlocked by KYN. 2OG and KYN functioned as an inhibitor and activator in response to changes in the concentrations of KYN and 2OG, respectively. The affinities of one subunit for PLP or 2OG were different from that of the other subunit, as confirmed by spectrophotometry and isothermal titration calorimetry, suggesting that the difference of affinities between subunits might play a role in regulations of the KAT reaction. Moreover, we identified two active and allosteric sites in the crystal structure of PhKAT-2OG complexes. The crystal structure of PhKAT in complex with four 2OGs demonstrates that two 2OGs in allosteric sites are effector molecules which inhibit the KYNA productions. Thus, the combined data lead to the conclusion that PhKAT probably is regulated by allosteric control machineries, with 2OG as the allosteric inhibitor. PMID:22792273

  20. Is Robin Hood Alive in Your Classroom?

    ERIC Educational Resources Information Center

    Royer, Sharon E.

    2002-01-01

    Considers whether the tales of Robin Hood should be presented as fact or fiction. Discusses the appropriateness of the tales for use in literature programs. Presents arguments for Robin Hood as fact and arguments for Robin Hood as fiction. Considers different versions of the tale. (SG)

  1. Systemic Induction of the Defensin and Phytoalexin Pisatin Pathways in Pea (Pisum sativum) against Aphanomyces euteiches by Acetylated and Nonacetylated Oligogalacturonides.

    PubMed

    Selim, Sameh; Sanssené, Jean; Rossard, Stéphanie; Courtois, Josiane

    2017-06-19

    Oligogalacturonides (OGs) are known for their powerful ability to stimulate the plant immune system but little is known about their mode of action in pea ( Pisum sativum ). In the present study, we investigated the elicitor activity of two fractions of OGs, with polymerization degrees (DPs) of 2-25, in pea against Aphanomyces euteiches . One fraction was nonacetylated (OGs - Ac) whereas the second one was 30% acetylated (OGs + Ac). OGs were applied by injecting the upper two rachises of the plants at three- and/or four-weeks-old. Five-week-old roots were inoculated with 10⁵ zoospores of A. euteiches . The root infection level was determined at 7, 10 and 14 days after inoculation using the quantitative real-time polymerase chain reaction (qPCR). Results showed significant root infection reductions namely 58, 45 and 48% in the plants treated with 80 µg OGs + Ac and 59, 56 and 65% with 200 µg of OGs - Ac. Gene expression results showed the upregulation of genes involved in the antifungal defensins, lignans and the phytoalexin pisatin pathways and a priming effect in the basal defense, SA and ROS gene markers as a response to OGs. The reduction of the efficient dose in OGs + Ac is suggesting that acetylation is necessary for some specific responses. Our work provides the first evidence for the potential of OGs in the defense induction in pea against Aphanomyces root rot.

  2. Girlhood, Sexual Violence, and Agency in Francesca Lia Block's "Wolf"

    ERIC Educational Resources Information Center

    Marshall, Elizabeth

    2009-01-01

    This essay examines the representation of adolescent girlhood, sexual violence and agency in Francesca Lia Block's contemporary fairy tale collection "The Rose and The Beast." Focusing specifically on the tale "Wolf," the author provides a literary analysis of how Block draws on and reworks traditional Western fairy tale variants to reintroduce…

  3. Reading, Writing, and "Rhythmetics" for the Verbally Gifted.

    ERIC Educational Resources Information Center

    Pilon, A. Barbara

    The monograph presents a variety of language arts teaching ideas for use with gifted students. Teachers are encouraged to expose children to much literature including poetry, folk tales, riddles, fairy tales, "pourquoi" tales, myths and legends, fantasy, science fiction, and biographies and autobiographies. The document offers the SIMMER theory of…

  4. It's No Secret: Fifty-eight Years of National Security Programs at BNL (463rd Brookhaven Lecture)

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

    Indusi, Joseph

    2010-11-17

    Prepare for a true tale of suspense and international intrigue. A tale that began in 1952, continued through the Cold War, and is not yet complete today. A tale of unexpected allies. Hear the true tale of one Laboratory’s efforts to keep nuclear materials out of the hands of evildoers. Freidlander. Higinbotham. Dodson. Kouts. And many more! See some of BNL’s all-star cast in the defining roles that shaped their careers as they worked toward keeping the nation and the world safe from the proliferation of nuclear weapons.

  5. The Teaching of Chaucer in Fifth and Sixth Forms.

    ERIC Educational Resources Information Center

    Brew, Trevor

    1967-01-01

    The teacher can sucessfully present Chaucer's "Canterbury Tales" to 11th- and 12th-grade students by concentrating on "The Prologue" and one of the tales--e.g., "The Pardoner's Tale." The structure and plan of the entire work, however, should first be considered before its various parts can be fully understood.…

  6. Unnatural substrates reveal the importance of 8-oxoguanine for in vivo mismatch repair by MutY

    PubMed Central

    Livingston, Alison L.; O’Shea, Valerie L.; Kim, Taewoo; Kool, Eric T.; David, Sheila S.

    2009-01-01

    Escherchia coli MutY plays an important role in preventing mutations associated with the oxidative lesion 7,8-dihydro-8-oxo-2′-deoxyguanosine (OG) in DNA by excising adenines from OG:A mismatches as the first step of base excision repair. To determine the importance of specific steps in the base pair recognition and base removal process of MutY, we have evaluated the effects of modifications of the OG:A substrate on the kinetics of base removal, mismatch affinity and repair to G:C in an Escherchia coli-based assay. Surprisingly, adenine modification was tolerated in the cellular assay, while modification of OG results in minimal cellular repair. High affinity for the mismatch and efficient base removal require the presence of OG. Taken together, these results suggest that the presence of OG is a critical feature for MutY to locate OG:A mismatches and select the appropriate adenines for excision to initiate repair in vivo prior to replication. PMID:18026095

  7. Green synthesized nickel nanoparticles for targeted detection and killing of S. typhimurium.

    PubMed

    Jeyaraj Pandian, Chitra; Palanivel, Rameshthangam; Balasundaram, Usha

    2017-09-01

    Simple and sensitive colorimetric immunosensor based on peroxidase mimetic activity and photothermal effect of nickel oxide nanoparticle (NiOGs) has been developed to detect and kill food borne pathogen Salmonella typhimurium. NiOGs showed superior peroxidase mimetic activity for oxidation of peroxidase substrate 3, 3', 5, 5'-tetramethylbenzidine (TMB). Oxidation of TMB by NiOGs followed Michaelis-Menten kinetics with K m and V max values of 0.25mM and 2.64×10 -8 M/s respectively. NiOGs was coated with citric acid (CA-NiOGs) followed by conjugation with antibody (anti-S. typhimurium) (Ab-CA-NiOGs) that effectively captured S. typhimurium. Colorimetric detection of S. typhimurium by Ab-CA-NiOGs showed a linear relationship between pathogen concentration (1×10 1 to 1×10 6 cfu/mL) and color signal (652nm) with limit of detection (LOD) of 10cfu/mL. The proposed method showed no cross reactivity against other pathogens. Recovery of S. typhimurium in milk and juice samples was found to be 95 to 100% and 92 to 99% respectively. NiOGs exposed to laser irradiation showed dose dependent increase in temperature and singlet oxygen within 5min. Bacteria bound to Ab-CA-NiOGs after laser irradiation, induced membrane damage and reduced bacterial viability to 6%. The bifunctional peroxidase-mimetic activity and photothermal effect of NiOGs can be exploited in selective sensing and killing of target pathogens respectively in food products. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Jeon, En Hee; Pak, Jung Hun; Kim, Mi Jin

    Highlights: Black-Right-Pointing-Pointer We isolated a novel E2 ubiquitin-conjugating enzyme from leaves of wild rice plants. Black-Right-Pointing-Pointer The OgUBC1 was highly expressed in leaves treated with SA and UV-B radiation. Black-Right-Pointing-Pointer The recombinant OgUBC1 has an enzymatic activity of E2 in vitro. Black-Right-Pointing-Pointer The OgUBC1 could protect disruption of plant cells by UV-B radiation. Black-Right-Pointing-Pointer OgUBC1 confers disease resistance and UV-B tolerance in transgenic Arabidopsis plants. -- Abstract: A previously unidentified gene encoding ubiquitin-conjugating enzyme was isolated from leaves of wild rice plant treated with wounding and microbe-associated molecular patterns. The OgUBC1 gene was composed of 148 amino acids and containedmore » a typical active site and 21 ubiquitin thioester intermediate interaction residues and 4 E3 interaction residues. Both exogenous application of salicylic acid and UV-B irradiation triggered expression of OgUBC1 in leaves of wild rice. Recombinant OgUBC1 proteins bound to ubiquitins in vitro, proposing that the protein might act as E2 enzyme in planta. Heterologous expression of the OgUBC1 in Arabidopsis thaliana protected plants from cellular damage caused by an excess of UV-B radiation. A stable expression of chalcone synthase gene was detected in leaves of OgUBC1-expressing Arabidopsis, resulting in producing higher amounts of anthocyanin than those in wild-type Col-0 plants. Additionally, both pathogenesis-related gene1 and 5 were transcribed in the transgenic Arabidopsis in the absence of pathogen infection. The OgUBC1-expressing plants were resistant to the infection of Botrytis cinerea. Taken together, we suggested that the OgUBC1 is involved in ubiquitination process important for cellular response against biotic and abiotic stresses in plants.« less

  9. Energy balance-dependent regulation of ovine glucose 6-phosphate dehydrogenase protein isoform expression.

    PubMed

    Triantaphyllopoulos, Kostas A; Laliotis, George P; Bizelis, Iosif A

    2014-01-01

    G6PDH is the rate-limiting enzyme of the pentose phosphate pathway and one of the principal source of NADPH, a major cellular reductant. Importantly, in ruminant's metabolism the aforementioned NADPH provided, is utilized for de novo fatty acid synthesis. Previous work of cloning the ovine (Ovis aries) og6pdh gene has revealed the presence of two cDNA transcripts (og6pda and og6pdb), og6pdb being a product of alternative splicing not similar to any other previously reported.(1) In the current study the effect of energy balance in the ovine G6PDH protein expression was investigated, shedding light on the biochemical features and potential physiological role of the oG6PDB isoform. Changes in energy balance leads to protein expression changes in both transcripts, to the opposite direction and not in a proportional way. Negative energy balance was not in favor of the presence of any particular isoform, while both protein expression levels were not significantly different (P > 0.05). In contrast, at the transition point from negative to positive and on the positive energy balance, there is a significant increase of oG6PDA compared with oG6PDB protein expression (P < 0.001). Both oG6PDH protein isoforms changed significantly toward the positive energy balance. oG6PDA is escalating, while oG6PDB is falling, under the same stimulus (positive energy balance alteration). This change is also positively associated with increasing levels in enzyme activity, 4 weeks post-weaning in ewes' adipose tissue. Furthermore, regression analysis clearly demonstrated the linear correlation of both proteins in response to the WPW, while energy balance, enzyme activity, and oG6PDA relative protein expression follow the same escalating trend; in contrast, oG6PDB relative protein expression falls in time, similar to both transcripts accumulation pattern, as reported previously.(2.)

  10. High-pressure Infrared Spectra of Tal and Lawsonite

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

    Scott,H.; Liu, Z.; Hemley, R.

    2007-01-01

    We present high-pressure infrared spectra of two geologically important hydrous minerals: talc, Mg3Si4O10(OH)2 and lawsonite, CaAl2Si2O7(OH)2{center_dot}H2O,{center_dot}at room temperature. For lawsonite, our data span the far infrared region from 150 to 550 cm-1 and extend to 25 GPa. We combine our new spectroscopic data with previously published high-pressure mid-infrared and Raman data to constrain the Gr{umlt u}neisen parameter and vibrational density of states under pressure. In the case of talc, we present high-pressure infrared data that span both the mid and far infrared from 150 to 3800 cm-1 covering lattice, silicate, and hydroxyl stretching vibrations to a maximum pressure of 30more » GPa. Both phases show remarkable metastability well beyond their nominal maximum thermodynamic stability at simultaneous high-pressure and high-temperature conditions.« less

  11. Composing Storied Ground: Four Generations of Narrative Inquiry

    ERIC Educational Resources Information Center

    Schaafsma, David; Pagnucci, Gian; Wallace, Rob; Stock, Patricia Lambert

    2007-01-01

    Narrative inquiry in English education comes in many shapes and forms--tales of classrooms and communities, didactic argu-stories, postmodern pastiches, open tales with O. Henry endings--but the heart of the enterprise is research in the form of story or, in other words, exploring the world by telling a story about it. In many such tales, all of…

  12. It's No Secret: Fifty-eight Years of National Security Programs at BNL (463rd Brookhaven Lecture)

    ScienceCinema

    Indusi, Joseph [BNL Nonproliferation and National Security Department

    2017-12-09

    Prepare for a true tale of suspense and international intrigue. A tale that began in 1952, continued through the Cold War, and is not yet complete today. A tale of unexpected allies. Hear the true tale of one Laboratory’s efforts to keep nuclear materials out of the hands of evildoers. Freidlander. Higinbotham. Dodson. Kouts. And many more! See some of BNL’s all-star cast in the defining roles that shaped their careers as they worked toward keeping the nation and the world safe from the proliferation of nuclear weapons.

  13. OGS#PETSc approach for robust and efficient simulations of strongly coupled hydrothermal processes in EGS reservoirs

    NASA Astrophysics Data System (ADS)

    Watanabe, Norihiro; Blucher, Guido; Cacace, Mauro; Kolditz, Olaf

    2016-04-01

    A robust and computationally efficient solution is important for 3D modelling of EGS reservoirs. This is particularly the case when the reservoir model includes hydraulic conduits such as induced or natural fractures, fault zones, and wellbore open-hole sections. The existence of such hydraulic conduits results in heterogeneous flow fields and in a strengthened coupling between fluid flow and heat transport processes via temperature dependent fluid properties (e.g. density and viscosity). A commonly employed partitioned solution (or operator-splitting solution) may not robustly work for such strongly coupled problems its applicability being limited by small time step sizes (e.g. 5-10 days) whereas the processes have to be simulated for 10-100 years. To overcome this limitation, an alternative approach is desired which can guarantee a robust solution of the coupled problem with minor constraints on time step sizes. In this work, we present a Newton-Raphson based monolithic coupling approach implemented in the OpenGeoSys simulator (OGS) combined with the Portable, Extensible Toolkit for Scientific Computation (PETSc) library. The PETSc library is used for both linear and nonlinear solvers as well as MPI-based parallel computations. The suggested method has been tested by application to the 3D reservoir site of Groß Schönebeck, in northern Germany. Results show that the exact Newton-Raphson approach can also be limited to small time step sizes (e.g. one day) due to slight oscillations in the temperature field. The usage of a line search technique and modification of the Jacobian matrix were necessary to achieve robust convergence of the nonlinear solution. For the studied example, the proposed monolithic approach worked even with a very large time step size of 3.5 years.

  14. Olumacostat glasaretil, a novel topical sebum inhibitor, in the treatment of acne vulgaris: A phase IIa, multicenter, randomized, vehicle-controlled study.

    PubMed

    Bissonnette, Robert; Poulin, Yves; Drew, Janice; Hofland, Hans; Tan, Jerry

    2017-01-01

    Olumacostat glasaretil (OG) inhibits acetyl-coenzyme A carboxylase, the enzyme responsible for the first, rate-limiting step in de novo fatty acid synthesis. OG inhibited in vitro human sebocyte lipid production and reduced in vivo sebaceous gland size in hamster ears. Safety and efficacy of OG 7.5% gel were evaluated in patients with moderate to severe facial acne vulgaris. Patients were randomized (1:1) to twice-daily application of OG or vehicle for 12 weeks. Efficacy was measured through changes in lesion counts and improvement in acne severity scores. A total of 108 patients received OG (n = 53) or vehicle (n = 55); these groups had mean baseline counts of 29.7 and 28.6 inflammatory and 40.9 and 38.8 noninflammatory lesions, respectively. At week 12, OG treatment showed greater reductions from baseline in inflammatory lesions (-63.9% vs -45.9%; P = .0006) and noninflammatory lesions (-48.1% vs -28.8%; P = .0025), and more patients with greater than or equal to 2-grade improvement in investigator global assessment score (24.5% vs 7.3%; P = .0070) than vehicle. Application-site adverse events (typically mild or moderate intensity) were more common with OG. Larger trials are needed to optimize OG dosing and confirm the current results. OG was well tolerated and showed evidence of efficacy, suggesting further development is warranted. Copyright © 2016. Published by Elsevier Inc.

  15. Folktale Frenzy: WebQuest Writing.

    ERIC Educational Resources Information Center

    Gaines, Lisa

    This folktale unit supports 6th- through 8th-grade students exploration of the many subgenres of folktales: trickster tales, fairy tales, fables, tall tales, and legends. The unit focuses heavily on the use of technology as a learning tool as students work together to create WebQuests for their peers to explore. During the 10 one-hour sessions,…

  16. Methylation effect on chalcone synthase gene expression determines anthocyanin pigmentation in floral tissues of two Oncidium orchid cultivars.

    PubMed

    Liu, Xiao-Jing; Chuang, Yao-Nung; Chiou, Chung-Yi; Chin, Dan-Chu; Shen, Fu-Quan; Yeh, Kai-Wun

    2012-08-01

    The anthocyanin-biosynthetic pathway was studied in flowers of Oncidium Gower Ramsey with yellow floral color and mosaic red anthocyanin in lip crests, sepals and petals, and compared with the anthocyanin biosynthesis in flowers of Oncidium Honey Dollp, a natural somatoclone derived from tissue culture of Gower Ramsey, with a yellow perianth without red anthocyanins in floral tissues. HPLC analysis revealed that the red anthocyanin in lip crests of the Gower Ramsey cultivar comprised peonidin-3-O-glucoside, delphinidin-3-O-glucoside and cyanidin-3-O-glucoside, whereas Honey Dollp was devoid of anthocyanin compounds. Among the five anthocyanin-biosynthetic genes, OgCHS was actively expressed in lip crests of Gower Ramsey flowers, but no transcripts of OgCHS were detected in Honey Dollp floral tissues. Transient expression of OgCHS by bombardment confirmed that recovery of the OgCHS gene expression completed the anthocyanin pathway and produced anthocyanin compounds in lip crests of Honey Dollp flowers. Transcription factor genes regulating anthocyanin biosynthesis showed no distinctive differences in the expression level of OgMYB1, OgbHLH and OgWD40 between the two cultivars. A methylation assay revealed that the promoter of OgCHS was not methylated in Gower Ramsey, while a positive methylation effect was present in the upstream promoter region of OgCHS in Honey Dollp. Overall, our results suggest that the failure of anthocyanin accumulation in Honey Dollp floral tissues may be attributed to inactivation of the OgCHS gene resulting from the epigenetic methylation of 5'-upstream promoter region.

  17. Cyclic guanosine monophosphate responses to atrial natriuretic factor, brain natriuretic peptide, but not C-type natriuretic peptide, and the characterization of their receptors in rat medullary thick ascending limb.

    PubMed

    Luk, J K; Wong, E F; Sun, A; Wong, N L

    1994-12-01

    The effects of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) on renal medullary thick ascending limb (mTAL) have not been fully understood. The aim of this study is to examine the second-messenger responses of rat mTAL to ANF, BNP, and CNP. Characterizations of the ANF, BNP, and CNP receptors in mTAL were also performed by radioligand studies. Results showed that ANF and BNP were both capable of eliciting cyclic guanosine monophosphate (cGMP) responses in mTAL. Conversely, no cGMP response was observed upon stimulation by CNP in mTAL. The presence of ANF receptors was demonstrated by radioligand studies. One receptor site was found, and the Kd and maximum binding capacity were 4.0 +/- 0.45 nmol/L and 277.8 +/- 47.7 fmol/mg protein, respectively. BNP receptors were also found in mTAL, and ANF and BNP were sharing the same receptor. On the contrary, no CNP receptor could be shown by radioligand studies. These results suggest that guanylyl cyclase-coupled receptors (atrial natriuretic peptide receptor-A [ANPR-A]) specific for ANF and BNP are present in rat mTAL, while those for CNP (ANPR-B) are absent. ANF and BNP but not CNP act on mTAL to control water excretion.

  18. Development of a see-through hollow cathode discharge lamp for (Li/Ne) optogalvanic studies

    NASA Astrophysics Data System (ADS)

    Saini, V. K.; Kumar, P.; Sarangpani, K. K.; Dixit, S. K.; Nakhe, S. V.

    2017-09-01

    Development of a demountable and see-through hollow cathode (HC) discharge lamp suitable for optogalvanic (OG) spectroscopy is described. The design of the HC lamp is simple, compact, and inexpensive. Lithium, investigated rarely by the OG method, is selected for cathode material as its isotopes are important for nuclear industry. The HC lamp is characterized electrically and optically for discharge oscillations free OG effect. Strong OG signals of lithium as well as neon (as buffer gas) are produced precisely upon copper vapor laser pumped tunable dye laser irradiation. The HC lamp is capable of generating a clean OG resonance spectrum in the available dye laser wavelength scanning range (627.5-676 nm) obtained with 4-(Dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran dye. About 28 resonant OG lines are explicitly observed. Majority of them have been identified using j-l coupling scheme and assigned to the well-known neon transitions. One line that corresponds to wavelength near about 670.80 nm is assigned to lithium and resolved for its fine (2S1/2 → 2P1/2, 3/2) transitions. These OG transitions allow 0.33 cm-1 accuracy and can be used to supplement the OG transition data available from other sources to calibrate the wavelength of a scanning dye laser with precision at atomic levels.

  19. Development of a see-through hollow cathode discharge lamp for (Li/Ne) optogalvanic studies.

    PubMed

    Saini, V K; Kumar, P; Sarangpani, K K; Dixit, S K; Nakhe, S V

    2017-09-01

    Development of a demountable and see-through hollow cathode (HC) discharge lamp suitable for optogalvanic (OG) spectroscopy is described. The design of the HC lamp is simple, compact, and inexpensive. Lithium, investigated rarely by the OG method, is selected for cathode material as its isotopes are important for nuclear industry. The HC lamp is characterized electrically and optically for discharge oscillations free OG effect. Strong OG signals of lithium as well as neon (as buffer gas) are produced precisely upon copper vapor laser pumped tunable dye laser irradiation. The HC lamp is capable of generating a clean OG resonance spectrum in the available dye laser wavelength scanning range (627.5-676 nm) obtained with 4-(Dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran dye. About 28 resonant OG lines are explicitly observed. Majority of them have been identified using j-l coupling scheme and assigned to the well-known neon transitions. One line that corresponds to wavelength near about 670.80 nm is assigned to lithium and resolved for its fine ( 2 S 1/2 → 2 P 1/2, 3/2 ) transitions. These OG transitions allow 0.33 cm -1 accuracy and can be used to supplement the OG transition data available from other sources to calibrate the wavelength of a scanning dye laser with precision at atomic levels.

  20. A transcription activator-like effector induction system mediated by proteolysis

    PubMed Central

    Copeland, Matthew F.; Politz, Mark C.; Johnson, Charles B.; Markley, Andrew L.; Pfleger, Brian F.

    2016-01-01

    Simple and predictable trans-acting regulatory tools are needed in the fields of synthetic biology and metabolic engineering to build complex genetic circuits and optimize the levels of native and heterologous gene products. Transcription activator-like effectors (TALEs) are bacterial virulence factors that have recently gained traction in biotechnology applications due to their customizable DNA binding specificity. In this work we expand the versatility of these transcription factors to create an inducible TALE system by inserting tobacco-etch virus (TEV) protease recognition sites into the TALE backbone. The resulting engineered TALEs maintain transcriptional repression of their target genes in Escherichia coli, but are degraded following the induction of the TEV protease, thereby promoting expression of the previously repressed target gene of interest. This TALE-TEV technology enables both repression and induction of plasmid or chromosomal target genes in a manner analogous to traditional repressor proteins but with the added flexibility of being operator agnostic. PMID:26854666

  1. Triacetic acid lactone production in industrial Saccharomyces yeast strains

    USDA-ARS?s Scientific Manuscript database

    Triacetic acid lactone (TAL) is a potential platform chemical that can be produced in yeast. To evaluate the potential for industrial yeast strains to produce TAL, the g2ps1 gene encoding 2-pyrone synthase was transformed into thirteen industrial yeast strains of varied genetic background. TAL produ...

  2. The use of the osmole gap as a screening test for the presence of exogenous substances.

    PubMed

    Purssell, Roy A; Lynd, Larry D; Koga, Yoshikata

    2004-01-01

    The rapid and accurate diagnosis of toxic alcohol poisoning due to methanol (methyl alcohol) [MeOH] and ethylene glycol (EG), is paramount in preventing serious adverse outcomes. The quantitative measurement of specific serum levels of these substances using gas chromatography is expensive, time consuming and generally only available at major tertiary-care facilities. Therefore, because these toxic substances are osmotically active and the measurement of serum osmolality is easily performed and more readily available, the presence of an osmole gap (OG) has been adopted as an alternative screening test. By definition, the OG is the difference between the measured serum osmolality determined using the freezing point depression (Osm(m)) and the calculated serum molarity (Mc), which is estimated from the known and readily measurable osmotically active substances in the serum, in particular sodium, urea, glucose, and potassium and ethanol (alcohol). Thus, the OG=Osm(m)-Mc, and an OG above a specific threshold (the threshold of positivity) suggests the presence of unmeasured osmotically active substances, which could be indicative of a toxic exposure. The objectives of this study were to review the principles of evaluating screening tests, the theory behind the OG as a screening test and the literature upon which the adoption of the OG as a screening test has been based. This review revealed that there have been numerous equations derived and proposed for the estimation of the Mc, with the objective of developing empirical evidence of the best equation for the determination of the OG and ultimately the utility of OG as a screening test. However, the methods and statistical analysis employed have generally been inconsistent with recommended guidelines for screening test evaluation and although many equations have been derived, they have not been appropriately validated. Specific evidence of the clinical utility of the OG requires that a threshold of positivity be

  3. 50 CFR 648.292 - Tilefish specifications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... available data to determine if the ACL, ACT, or total allowable landings (TAL) requires modification to... that review, the Monitoring Committee will recommend ACL, ACT, and TAL to the Tilefish Committee of the... recommend to the MAFMC the appropriate ACL, ACT, TAL, and other management measures for a single fishing...

  4. 50 CFR 648.292 - Tilefish specifications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... available data to determine if the ACL, ACT, or total allowable landings (TAL) requires modification to... that review, the Monitoring Committee will recommend ACL, ACT, and TAL to the Tilefish Committee of the... recommend to the MAFMC the appropriate ACL, ACT, TAL, and other management measures for a single fishing...

  5. 50 CFR 648.292 - Tilefish specifications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... available data to determine if the ACL, ACT, or total allowable landings (TAL) requires modification to... that review, the Monitoring Committee will recommend ACL, ACT, and TAL to the Tilefish Committee of the... recommend to the MAFMC the appropriate ACL, ACT, TAL, and other management measures for a single fishing...

  6. 50 CFR 648.292 - Tilefish specifications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... available data to determine if the ACL, ACT, or total allowable landings (TAL) requires modification to... that review, the Monitoring Committee will recommend ACL, ACT, and TAL to the Tilefish Committee of the... recommend to the MAFMC the appropriate ACL, ACT, TAL, and other management measures for a single fishing...

  7. Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue.

    PubMed

    Dougherty, John P; Wolff, Brian S; Cullen, Mary J; Saligan, Leorey N; Gershengorn, Marvin C

    2017-10-01

    Fatigue affects most cancer patients and has numerous potential causes, including cancer itself and cancer treatment. Cancer-related fatigue (CRF) is not relieved by rest, can decrease quality of life, and has no FDA-approved therapy. Thyrotropin-releasing hormone (TRH) has been proposed as a potential novel treatment for CRF, but its efficacy against CRF remains largely untested. Thus, we tested the TRH analog, taltirelin (TAL), in mouse models of CRF. To model fatigue, we used a mouse model of chemotherapy, a mouse model of radiation therapy, and mice bearing colon 26 carcinoma tumors. We used the treadmill fatigue test to assess fatigue-like behavior after treatment with TAL. Additionally, we used wild-type and TRH receptor knockout mice to determine which TRH receptor was necessary for the actions of TAL. Tumor-bearing mice displayed muscle wasting and all models caused fatigue-like behavior, with mice running a shorter distance in the treadmill fatigue test than controls. TAL reversed fatigue-like behavior in all three models and the mouse TRH 1 receptor was necessary for the effects of TAL. These data suggest that TAL may be useful in alleviating fatigue in all cancer patients and provide further support for evaluating TAL as a potential therapy for CRF in humans. Published by Elsevier Ltd.

  8. Does topical lidocaine before tracheal intubation attenuate airway responses in children? An observational audit.

    PubMed

    Hamilton, Nigel D; Hegarty, Mary; Calder, Alyson; Erb, Thomas O; von Ungern-Sternberg, Britta S

    2012-04-01

    The use of topical lidocaine, applied to the airways with various administration techniques, is common practice in pediatric anesthesia in many institutions. However, it remains unclear whether these practices achieve their intended goal of reducing the risk of perioperative respiratory adverse events (PRAE) in children undergoing elective endotracheal intubation without neuromuscular blockade (NMB). The relative frequency of PRAE (laryngospasm, coughing, desaturation <95%) associated with no use of topical airway lidocaine (TAL), with TAL sprayed directly onto the vocal cords, and TAL administered blindly into the pharynx was assessed. This prospective audit involved 1000 patients undergoing general anesthesia with elective endotracheal intubation without NMB. Patients with suspected difficult airways or undergoing airway surgery were excluded. The use of TAL and the mode of administration were recorded. Respiratory adverse events were recorded in the perioperative period. Two hundred and fifty-four patients had the vocal cords sprayed under direct vision, 236 had lidocaine blindly dripped into the pharynx, and 510 received no TAL. The mean age and known risk factors for PRAE (asthma, recent upper respiratory tract infection (≤2 weeks), passive smoking, hayfever, past or present eczema, nocturnal dry cough) were similar among the groups. The proportion of patients with desaturation (<95%) between induction of anesthesia and discharge from the recovery room was higher in the two groups who received TAL (data combined for all patients receiving lidocaine regardless of administration method, P = 0.01) compared to those who received no TAL. No difference in the rates of laryngospasm (P = 0.13) or cough (P = 0.07) was observed among the groups. There was no difference in the rates of PRAE between the groups given TAL directly onto the vocal cords and in those whom received TAL blindly. The incidence of desaturation was higher in patients receiving TAL compared with

  9. TRPV4 activation mediates flow-induced nitric oxide production in the rat thick ascending limb

    PubMed Central

    Garvin, Jeffrey L.

    2014-01-01

    Nitric oxide (NO) regulates renal function. Luminal flow stimulates NO production in the thick ascending limb (TAL). Transient receptor potential vanilloid 4 (TRPV4) is a mechano-sensitive channel activated by luminal flow in different types of cells. We hypothesized that TRPV4 mediates flow-induced NO production in the rat TAL. We measured NO production in isolated, perfused rat TALs using the fluorescent dye DAF FM. Increasing luminal flow from 0 to 20 nl/min stimulated NO from 8 ± 3 to 45 ± 12 arbitrary units (AU)/min (n = 5; P < 0.05). The TRPV4 antagonists, ruthenium red (15 μmol/l) and RN 1734 (10 μmol/l), blocked flow-induced NO production. Also, luminal flow did not increase NO production in the absence of extracellular calcium. We also studied the effect of luminal flow on NO production in TALs transduced with a TRPV4shRNA. In nontransduced TALs luminal flow increased NO production by 47 ± 17 AU/min (P < 0.05; n = 5). Similar to nontransduced TALs, luminal flow increased NO production by 39 ± 11 AU/min (P < 0.03; n = 5) in TALs transduced with a control negative sequence-shRNA while in TRPV4shRNA-transduced TALs, luminal flow did not increase NO production (Δ10 ± 15 AU/min; n = 5). We then tested the effect of two different TRPV4 agonists on NO production in the absence of luminal flow. 4α-Phorbol 12,13-didecanoate (1 μmol/l) enhanced NO production by 60 ± 11 AU/min (P < 0.002; n = 7) and GSK1016790A (10 ηmol/l) increased NO production by 52 ± 15 AU/min (P < 0.03; n = 5). GSK1016790A (10 ηmol/l) did not stimulate NO production in TRPV4shRNA-transduced TALs. We conclude that activation of TRPV4 channels mediates flow-induced NO production in the rat TAL. PMID:24966090

  10. Environmental and Human Health Impacts of Spreading Oil and Gas Wastewater on Roads.

    PubMed

    Tasker, T L; Burgos, W D; Piotrowski, P; Castillo-Meza, L; Blewett, T A; Ganow, K B; Stallworth, A; Delompré, P L M; Goss, G G; Fowler, L B; Vanden Heuvel, J P; Dorman, F; Warner, N R

    2018-06-19

    Thirteen states in the United States allow the spreading of O&G wastewaters on roads for deicing or dust suppression. In this study, the potential environmental and human health impacts of this practice are evaluated. Analyses of O&G wastewaters spread on roads in the northeastern, U.S. show that these wastewaters have salt, radioactivity, and organic contaminant concentrations often many times above drinking water standards. Bioassays also indicated that these wastewaters contain organic micropollutants that affected signaling pathways consistent with xenobiotic metabolism and caused toxicity to aquatic organisms like Daphnia magna. The potential toxicity of these wastewaters is a concern as lab experiments demonstrated that nearly all of the metals from these wastewaters leach from roads after rain events, likely reaching ground and surface water. Release of a known carcinogen (e.g., radium) from roads treated with O&G wastewaters has been largely ignored. In Pennsylvania from 2008 to 2014, spreading O&G wastewater on roads released over 4 times more radium to the environment (320 millicuries) than O&G wastewater treatment facilities and 200 times more radium than spill events. Currently, state-by-state regulations do not require radium analyses prior to treating roads with O&G wastewaters. Methods for reducing the potential impacts of spreading O&G wastewaters on roads are discussed.

  11. Unmatched speed perceptions between overground and treadmill manual wheelchair propulsion in long-term manual wheelchair users.

    PubMed

    Chénier, Félix; Champagne, Audrey; Desroches, Guillaume; Gagnon, Dany H

    2018-03-01

    Manual wheelchair (MWC) propulsion is increasingly assessed on a motorized treadmill (TM), which is often considered more ecologically valid than stationary rollers. However, no clear consensus on the similarities between overground (OG) and TM propulsion has yet been reached. Furthermore, no study has investigated the participants' perceptions of propelling a MWC on a TM compared to OG. The present study aims to assess the perception of speed when propelling on a TM vs OG, and to relate this perception to measured spatiotemporal variables, kinetics and work. In this repeated-measures study, the propulsion's spatiotemporal variables, kinetics, and work of nineteen experienced wheelchair users with a spinal cord injury were compared between three conditions: 1) OG at a self-selected speed, 2) on a TM at a self-selected speed perceived as being similar to the OG speed (TM perceived ), and 3) on a TM at the same speed as OG (TM matched ). Each variable was compared between conditions using an analysis of variance for repeated measures. All participants selected a lower speed for TM perceived than OG, with a difference of -0.6 m/s (-44%). This adaptation may be due to a combination of two factors: 1) the absence of speed information, and 2) the feeling of urgency to grab the wheels during the recovery phase. The power output, work per cycle, and work per minute were also much lower on TM perceived than OG. However, in contrast to other work on MWC propulsion on a TM, the kinetic variables assessed were all similar between the OG and TM matched conditions. Training on a TM should be performed at a speed that matches the OG speed and not at a self-selected speed on the TM, which would reduce the power output and work and therefore reduce the efficiency of the training. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Methanol extract of Ocimum gratissimum protects murine peritoneal macrophages from nicotine toxicity by decreasing free radical generation, lipid and protein damage and enhances antioxidant protection

    PubMed Central

    Mahapatra, Santanu Kar; Chakraborty, Subhankari Prasad; Das, Subhasis

    2009-01-01

    In the present study, methanol extract of Ocimum gratissimum Linn (ME-Og) was tested against nicotine-induced murine peritoneal macrophage in vitro. Phytochemical analysis of ME-Og shown high amount of flavonoid and phenolic compound present in it. The cytotoxic effect of ME-Og was studied in murine peritoneal macrophages at different concentrations (0.1 to 100 µg/ml) using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) method. To establish the protective role of ME-Og against nicotine toxicity, peritoneal macrophages from mice were treated with nicotine (10 mM), nicotine + ME-Og (1 to 25 µg/ml) for 12 h in culture media. The significantly (p < 0.05) increased super oxide anion generation, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, myeloperoxidase (MPO) activity, lipid peroxidation, protein carbonyls, oxidized glutathione levels were observed in nicotine-treated group as compared to control group; those were significantly (p < 0.05) reduced in ME-Og supplemented groups in concentration dependent manner. More over, significantly (p < 0.05) reduced antioxidant status due to nicotine exposure was effectively ameliorated by ME-Og supplementation in murine peritoneal macrophages. Among the different concentration of ME-Og, maximum protective effect was observed by 25 µg/ml, which does not produce significant cell cytotoxicity in murine peritoneal macrophages. These findings suggest the potential use and beneficial role of O. gratissimum as a modulator of nicotine-induced free radical generation, lipid-protein damage and antioxidant status in important immune cell, peritoneal macrophages. PMID:20716908

  13. Outcome of Laparoscopic Adrenalectomy in Obese Patients.

    PubMed

    Paun, Diana; Petris, Rodica; Ganescu, Roxana; Paun, Sorin; Vartic, Mihaela; Beuran, Mircea

    2015-09-01

    To compare early morbidity of obese and nonobese patients with minimally invasive adrenalectomies. Retrospective study of a prospectively maintained database, between June 2003 - December 2012, in a universitary affiliated tertiary hospital. Selection criteria: Minimally invasive adrenalectomy. Obese patients were defined as BMI over 30 kg/m2. From 205 patient with laparoscopic adrenalectomies we counted 30 obese patients (OG), 25 of them female and only 5 men with a median age of 54,20 years versus 47,94 years for nonobese group (NOG) (p=0.008). In OG were 15 right sided tumor, 11 on the left side and 4 bilateral all treated with transperitoneal antero-lateral approach. Median operating time was 92.20 minutes for OG versus 91.13 minutes for NOG (p=0.924). In OG, 5 patients had previous abdominal surgeries and we counted 4 conversion to open surgery, 2 postoperative complications (6.6%) and no mortality. All OG patients have diverse comorbidities, 50% of them more then 3. Median specimen size was 5.92 cm for OG versus 4.85 cm for NOG (p=0.057). The histology of OG was: adenoma 11 cases, hiperplasia 13 cases and pheochromocytoma 6. In NOG we had: postoperative hospital stay was 6.57 days in OG versus 4.11 days in NOG (p=0.009). Although obese patients had a higher rate for early morbidities, the minimally invasive approach has particular benefits for them. Although postoperative hospital stay was significantly longer, we believe that advantages of minimal invasive surgery for obese patients remains valid even in a BMI over 30.

  14. Octyl gallate reduces ATP levels and Ki67 expression leading HepG2 cells to cell cycle arrest and mitochondria-mediated apoptosis.

    PubMed

    Lima, Kelly Goulart; Krause, Gabriele Catyana; da Silva, Elisa Feller Gonçalves; Xavier, Léder Leal; Martins, Léo Anderson Meira; Alice, Laura Manzoli; da Luz, Luiza Bueno; Gassen, Rodrigo Benedetti; Filippi-Chiela, Eduardo Cremonese; Haute, Gabriela Viegas; Garcia, Maria Claudia Rosa; Funchal, Giselle Afonso; Pedrazza, Leonardo; Reghelin, Camille Kirinus; de Oliveira, Jarbas Rodrigues

    2018-04-01

    Octyl gallate (OG) is an antioxidant that has shown anti-tumor, anti-diabetic and anti-amyloidogenic activities. Mitochondria play an important role in hepatocellular carcinoma, mainly by maintaining accelerated cellular proliferation through the production of ATP. Thus, the mitochondria may be a target for antitumor therapies. Here, we investigated the effects of OG in the hepatocarcinoma cell line (HepG2) and the mechanisms involved. We report, for the first time, that treatment with OG for 24h inhibited HepG2 cell growth by decreasing mitochondrial activity and mass, which led to the reduction of ATP levels. This reduction in the energy supply triggered a decrease in Ki67 protein expression, leading cells to cycle arrest. In addition, treatment with two doses of OG for 48h induced loss of mitochondrial functionality, mitochondrial swelling and apoptosis. Finally, we report that HepG2 cells had no resistance to treatment after multiple doses. Collectively, our findings indicate that metabolic dysregulation and Ki67 protein reduction are key events in the initial anti-proliferative action of OG, whereas mitochondrial swelling and apoptosis induction are involved in the action mechanism of OG after prolonged exposure. This suggests that OG targets mitochondria, thus representing a candidate for further research on therapies for hepatocarcinoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. 2-Oxoglutarate levels control adenosine nucleotide binding by Herbaspirillum seropedicae PII proteins.

    PubMed

    Oliveira, Marco A S; Gerhardt, Edileusa C M; Huergo, Luciano F; Souza, Emanuel M; Pedrosa, Fábio O; Chubatsu, Leda S

    2015-12-01

    Nitrogen metabolism in Proteobacteria is controlled by the Ntr system, in which PII proteins play a pivotal role, controlling the activity of target proteins in response to the metabolic state of the cell. Characterization of the binding of molecular effectors to these proteins can provide information about their regulation. Here, the binding of ATP, ADP and 2-oxoglutarate (2-OG) to the Herbaspirillum seropedicae PII proteins, GlnB and GlnK, was characterized using isothermal titration calorimetry. Results show that these proteins can bind three molecules of ATP, ADP and 2-OG with homotropic negative cooperativity, and 2-OG binding stabilizes the binding of ATP. Results also show that the affinity of uridylylated forms of GlnB and GlnK for nucleotides is significantly lower than that of the nonuridylylated proteins. Furthermore, fluctuations in the intracellular concentration of 2-OG in response to nitrogen availability are shown. Results suggest that under nitrogen-limiting conditions, PII proteins tend to bind ATP and 2-OG. By contrast, after an ammonium shock, a decrease in the 2-OG concentration is observed causing a decrease in the affinity of PII proteins for ATP. This phenomenon may facilitate the exchange of ATP for ADP on the ligand-binding pocket of PII proteins, thus it is likely that under low ammonium, low 2-OG levels would favor the ADP-bound state. © 2015 FEBS.

  16. Ocimum gratissimum retards breast cancer growth and progression and is a natural inhibitor of matrix metalloproteases

    PubMed Central

    Nangia-Makker, Pratima; Raz, Tirza; Tait, Larry; Shekhar, Malathy P.V.; Li, Hong; Balan, Vitaly; Makker, Hemanckur; Fridman, Rafael; Maddipati, Krishnarao; Raz, Avraham

    2013-01-01

    Ocimum genus (a.k.a holy basil or tulsi) is a dietary herb used for its multiple beneficial pharmacologic properties including anti-cancer activity. Here we show that crude extract of Ocimum gratissimum (OG) and its hydrophobic and hydrophilic fractions (HB and HL) differentially inhibit breast cancer cell chemotaxis and chemoinvasion in vitro and retard tumor growth and temporal progression of MCF10ADCIS.com xenografts, a model of human breast comedo-ductal carcinoma in situ (comedo-DCIS). OG-induced inhibition of tumor growth was associated with decreases in basement membrane disintegration, angiogenesis and MMP-2 and MMP-9 activities as confirmed by in situ gelatin zymography and cleavage of galectin-3. There was also decrease in MMP-2 and MMP-9 activities in the conditioned media of OG-treated MCF10AT1 and MCF10AT1-EIII8 premalignant human breast cancer cells as compared with control. The MMP-2 and MMP-9 inhibitory activities of OG were verified in vitro using gelatin, a synthetic fluorogenic peptide and recombinant galectin-3 as MMP substrates. Mice fed on OG-supplemented drinking water showed no adverse effects compared with control. These data suggest that OG is non-toxic and that the anti-cancer therapeutic activity of OG may in part be contributed by its MMP inhibitory activity. PMID:23380593

  17. Influence of Culture and Personality on Determinants of Cognitive Processes Under Conditions of Uncertainty

    DTIC Science & Technology

    2004-05-14

    Tal , Y., Raviv , A., & Spitzer, A., 1999). Janis and Mann (1977) suggested that situational conditions determine how individuals cope with decision...and ignore contrary information relative to non-stressful conditions, which can have disastrous consequences. Bar- Tal , Raviv , and Spitzer (1999...1176. Bar- Tal , Y., Raviv , A., & Spitzer, A. (1999). The need and ability to achieve cognitive structuring: Individual differences that moderate

  18. Operational Group Sandy technical progress report

    USGS Publications Warehouse

    ,

    2013-01-01

    This report documents results from the March 2013 deployment of the OGS. It includes background information on Hurricane Sandy and the federal response; the OGS methodology; scenarios for Hurricane Sandy’s impact on coastal communities and urban ecosystems; potential interventions to improve regional resilience to future major storms; a discussion of scenario results; and lessons learned about the OGS process.

  19. "Dear Bob . . . ."

    ERIC Educational Resources Information Center

    Kimmel, Eric A.

    1980-01-01

    A humorous presentation of publisher-to-author correspondence that indicates how contemporary publishers might criticize or reject such works as "Treasure Island,""The Tale of Peter Rabbit,""Little Women," and the Grimm brothers' fairy tales. (ET)

  20. A transcription activator-like effector from Xanthomonas oryzae pv. oryzicola elicits dose-dependent resistance in rice.

    PubMed

    Hummel, Aaron W; Wilkins, Katherine E; Wang, Li; Cernadas, R Andres; Bogdanove, Adam J

    2017-01-01

    Xanthomonas spp. reduce crop yields and quality worldwide. During infection of their plant hosts, many strains secrete transcription activator-like (TAL) effectors, which enter the host cell nucleus and activate specific corresponding host genes at effector binding elements (EBEs) in the promoter. TAL effectors may contribute to disease by activating the expression of susceptibility genes or trigger resistance associated with the hypersensitive reaction (HR) by activating an executor resistance (R) gene. The rice bacterial leaf streak pathogen X. oryzae pv. oryzicola (Xoc) is known to suppress host resistance, and no host R gene has been identified against it, despite considerable effort. To further investigate Xoc suppression of host resistance, we conducted a screen of effectors from BLS256 and identified Tal2a as an HR elicitor in rice when delivered heterologously by a strain of the closely related rice bacterial blight pathogen X. oryzae pv. oryzae (Xoo) or by the soybean pathogen X. axonopodis pv. glycines. The HR required the Tal2a activation domain, suggesting an executor R gene. Tal2a activity was differentially distributed among geographically diverse Xoc isolates, being largely conserved among Asian isolates. We identified four genes induced by Tal2a in next-generation RNA sequencing experiments and confirmed them using quantitative real-time reverse transcription-polymerase chain reaction (qPCR). However, neither individual nor collective activation of these genes by designer TAL effectors resulted in HR. A tal2a knockout mutant of BLS256 showed virulence comparable with the wild-type, but plasmid-based overexpression of tal2a at different levels in the wild-type reduced virulence in a directly corresponding way. Overall, the results reveal that host resistance suppression by Xoc plays a critical role in pathogenesis. Further, the dose-dependent avirulence activity of Tal2a and the apparent lack of a single canonical target that accounts for HR point to

  1. Converting Transaldolase into Aldolase through Swapping of the Multifunctional Acid-Base Catalyst: Common and Divergent Catalytic Principles in F6P Aldolase and Transaldolase.

    PubMed

    Sautner, Viktor; Friedrich, Mascha Miriam; Lehwess-Litzmann, Anja; Tittmann, Kai

    2015-07-28

    Transaldolase (TAL) and fructose-6-phosphate aldolase (FSA) both belong to the class I aldolase family and share a high degree of structural similarity and sequence identity. The molecular basis of the different reaction specificities (transferase vs aldolase) has remained enigmatic. A notable difference between the active sites is the presence of either a TAL-specific Glu (Gln in FSA) or a FSA-specific Tyr (Phe in TAL). Both residues seem to have analoguous multifunctional catalytic roles but are positioned at different faces of the substrate locale. We have engineered a TAL double variant (Glu to Gln and Phe to Tyr) with an active site resembling that of FSA. This variant indeed exhibits aldolase activity as its main activity with a catalytic efficiency even larger than that of authentic FSA, while TAL activity is greatly impaired. Structural analysis of this variant in complex with the dihydroxyacetone Schiff base formed upon substrate cleavage identifies the introduced Tyr (genuine in FSA) to catalyze protonation of the central carbanion-enamine intermediate as a key determinant of the aldolase reaction. Our studies pinpoint that the Glu in TAL and the Tyr in FSA, although located at different positions at the active site, similarly act as bona fide acid-base catalysts in numerous catalytic steps, including substrate binding, dehydration of the carbinolamine, and substrate cleavage. We propose that the different spatial positions of the multifunctional Glu in TAL and of the corresponding multifunctional Tyr in FSA relative to the substrate locale are critically controlling reaction specificity through either unfavorable (TAL) or favorable (FSA) geometry of proton transfer onto the common carbanion-enamine intermediate. The presence of both potential acid-base residues, Glu and Tyr, in the active site of TAL has deleterious effects on substrate binding and cleavage, most likely resulting from a differently organized H-bonding network. Large-scale motions of the

  2. Turf Tales

    ERIC Educational Resources Information Center

    DiConsiglio, John

    2009-01-01

    When it comes to raising money for college and university athletic programs, every professional knows how the game is played. Tickets drive the bus. In exchange for gifts, donors typically pay seat-licensing fees. This kind of "quid pro quo" giving--where generous contributions put one in position to buy good tickets--is a very common model," says…

  3. Doc Tales

    ERIC Educational Resources Information Center

    Golden, Larry; Alamia, Jennifer; Baker, Ria; Chilson, Sally; Choucroun, Pierre; Cook, Katrina; de Vries-Kell, Sabina; Marbach, Christina; Peters, Scott

    2005-01-01

    Acceptance into a doctoral program is personally affirming and gives rise to optimism. It is also true that any change in the life of a person, even an apparently positive one, causes stress. The first cohort of students in a new doctoral program in counseling writes about the impact of embarking on a doctorate on themselves and their significant…

  4. Fish Tales

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

    McLerran, L.

    2010-07-06

    This talk is about fishing and the friendships that have resulted in its pursuit. It is also about theoretical physics, and the relationship of imagination and fantasy to the establishment of ideas about nature. Fishermen, like theoretical physicists, are well known for their inventive imaginations. Perhaps neither are as clever as sailors, who conceived of the mermaid. If one doubts the power of this fantasy, one should remember the ghosts of the many sailors who drowned pursuing these young nymphs. An extraordinary painting by J. Waterhouse is shown as Fig. 1. The enchantment of a mermaid must reflect an extraordinarymore » excess of imagination on the part of the sailor, perhaps together with an impractical turn of mind. A consummated relationship with a mermaid is after all, by its very nature a fantasy incapable of realization. To a theoretical physicist, she is symbolic of many ideas we develop. There are many truths known to fisherman in which one might also find parallels to the goals of scientists: (1) A fish is the only animal that keeps growing after its death; (2) Nothing makes a fish bigger than almost being caught; (3) ''...of all the liars among mankind, the fisherman is the most trustworthy.'' (William Sherwood Fox, in Silken Lines and Silver Hooks); and (4) Men and fish are alike. They both get into trouble when they open their mouths. These quotes may be interpreted as reflecting skepticism regarding the honesty of fisherman, and probably do not reflect adequate admiration for a creative imagination. Is it fair to criticize a person for believing a falsehood that he or she sincerely believes to be true? The fisherman simultaneously invents the lie, and believes in it himself. The parallel with theoretical physics is perhaps only approximate, although we physicists may invent stories that we come to believe, on some rare occasions our ideas actually correspond to a more or less true descriptions of nature. These minor philosophical differences are not really the central issue, however. It is more to the point that both fishermen and scientists enjoy creating a good story, and we also enjoy a story well told. The correct mixture of truth, lie, fantasy and excitement is a witches brew.« less

  5. Snail Tales

    ERIC Educational Resources Information Center

    Phelps, Cynthia L.; Willcockson, Irmgard U.; Houtz, Lynne

    2004-01-01

    A team of teachers, scientists, and high school students at the University of Texas Health Science Center at Houston has developed activities to teach concepts in learning through an inquiry-based laboratory method. The Learning Education and Research Network (LEARN) activities were field tested at the Society for Neuroscience Conference, in the…

  6. Cautionary Tales

    ERIC Educational Resources Information Center

    Stuart, Reginald

    2010-01-01

    When Kemba Smith Pradia spoke this fall to a gathering of students at South Carolina State University, her candid talk about violence against women and the campus "hype" over drugs, sex, and money resonated with students and faculty alike. Ten years ago, Kemba Smith was wasting away in a federal prison as prisoner No. 26370-083. Used by…

  7. The opposite roles of agdA and glaA on citric acid production in Aspergillus niger.

    PubMed

    Wang, Lu; Cao, Zhanglei; Hou, Li; Yin, Liuhua; Wang, Dawei; Gao, Qiang; Wu, Zhenqiang; Wang, Depei

    2016-07-01

    Citric acid is produced by an industrial-scale process of fermentation using Aspergillus niger as a microbial cell factory. However, citric acid production was hindered by the non-fermentable isomaltose and insufficient saccharification ability in A. niger when liquefied corn starch was used as a raw material. In this study, A. niger TNA 101ΔagdA was constructed by deletion of the α-glucosidase-encoding agdA gene in A. niger CGMCC 10142 genome using Agrobacterium tumefaciens-mediated transformation. The transformants A. niger OG 1, OG 17, and OG 31 then underwent overexpression of glucoamylase in A. niger TNA 101ΔagdA. The results showed that the α-glucosidase activity of TNA 101ΔagdA was decreased by 62.5 % compared with CGMCC 10142, and isomaltose was almost undetectable in the fermentation broth. The glucoamylase activity of the transformants OG 1 and OG 17 increased by 34.5 and 16.89 % compared with that of TNA 101ΔagdA, respectively. In addition, for the recombinants TNA 101ΔagdA, OG 1 and OG 17, there were no apparent defects in the growth development. Consequently, in comparison with CGMCC 10142, TNA 101ΔagdA and OG 1 decreased the residual reducing sugar by 52.95 and 88.24 %, respectively, and correspondingly increased citric acid production at the end of fermentation by 8.68 and 16.87 %. Citric acid production was further improved by decreasing the non-fermentable residual sugar and increasing utilization rate of corn starch material in A. niger. Besides, the successive saccharification and citric acid fermentation processes were successfully integrated into one step.

  8. Detection of induced seismicity due to oil and gas extraction in the northern Gulf of Mexico, USA

    NASA Astrophysics Data System (ADS)

    Fadugba, Oluwaseun Idowu

    Drilling operations and extraction of oil and gas (O&G) may lead to subsurface slumping or compression of sediments due to reduced vertical principal stress which may lead to small earthquakes at the drilling site. O&G extraction is common in the northern Gulf of Mexico (NGM) and only thirty-five earthquakes of magnitudes between 2.3 and 6.0 have been recorded in the area from 1974 to the present. The purpose of this research is to detect more earthquakes using stacks of seismic data from the Transportable USArray (TA) from 2011 to 2013, and determine the spatiotemporal relationship between the detected earthquakes and O&G extraction. Five new small offshore earthquakes, that may be associated with the offshore O&G production, have been detected in the data. Spatial correlation of the epicenters with offshore drilling sites shows that the earthquakes may be due to the O&G extraction.

  9. K-8 Collection.

    ERIC Educational Resources Information Center

    Web Feet, 2001

    2001-01-01

    This annotated subject guide to Web sites for grades K-8 focuses on biography, dinosaurs, fairy tales and folk tales, history, math, science, and calendar connections for December observances. Specific grade levels are indicated for each annotation. (LRW)

  10. Elderly patients with colorectal cancer: treatment modalities and survival in France. National data from the ThInDiT cohort study.

    PubMed

    Doat, S; Thiébaut, A; Samson, S; Ricordeau, P; Guillemot, D; Mitry, E

    2014-05-01

    Few data exist on how elderly patients with colorectal cancer (CRC) are actually treated in real-life practice. Based on a national cohort, we analysed routine treatment modalities of the elderly who were diagnosed with CRC in France in 2009. The characteristics of patients and tumours and the cancer treatments received during the first year of all national incident cases of CRC diagnosed between 1st April and 31st December 2009, were compared between a 'younger group' (YG), under 75 years of age (N = 18,410 patients), and an 'older group' (OG), aged 75 and over (N = 13,255 patients). In the OG with metastases at baseline, we analysed two-year overall survival (OS) according to the treatment received (e.g. chemotherapy, surgery) and well-known prognostic factors. Among patients with localised CRC (N = 25,353), surgery was equally performed in both groups in more than 80% of the cases (p=0.52); time to surgery was shorter in the OG (8 versus 23 days) because there was more emergency surgery for occlusion among the OG. Adjuvant chemotherapy was performed in 15% of the OG (versus 29% in the YG) and consisted of 5-fluorouracil (5FU) monotherapy in more than 50% of OG patients. Among patients with metastatic CRC (N = 6,312), palliative chemotherapy was given to 48% of the OG versus 85% of the YG. Chemotherapy regimens included 30% monotherapy with 5FU, 30% oxaliplatin combination and 20% bevacizumab combination in the OG; compared to 10%, 34% and 35%, respectively, in the YG. The median OS for the OG was 8.4 months (versus 22.3 months in the YG) and 17.1 months among elderly patients who received chemotherapy. CRC is more frequently complicated at diagnosis among elderly patients. Adjuvant and palliative chemotherapy is less frequently prescribed among elderly patients. This could be explained by the fact that unfit elderly patients do not deserve chemotherapy, but certainly also reflect the fact that some fit elderly patients are undertreated. Copyright © 2014

  11. Medical abortions performed by specialists in private practice.

    PubMed

    Pay, Aase Serine Devold; Aabø, Runa Sigrid; Økland, Inger; Janbu, Torunn; Iversen, Ole-Erik; Løkeland, Mette

    2018-05-29

    I Norge utføres abort kun i offentlige sykehus. I 2010 besluttet Helse- og omsorgsdepartementet å iverksette et toårig prøveprosjekt som ga avtalespesialister i fødselshjelp og kvinnesykdommer adgang til å tilby medikamentell abort før utgangen av 9. svangerskapsuke. Prøveprosjektet ble igangsatt 1.3.2015 og varte til 31.3.2017. I denne artikkelen presenterer vi de første erfaringene, herunder hvordan behandlingstilbudet ble mottatt av kvinnene. Gravide med en svangerskapsvarighet < 63 dager ultrasonografisk vurdert, som oppsøkte avtalespesialist for medikamentell abort, ble fortløpende inkludert i prosjektet (n = 476). Kvinnene inntok 200 mg mifepriston peroralt på legekontoret, 36-48 timer senere satte de selv 800 µg misoprostol vaginalt hjemme. Informasjon ble innhentet ved spørreskjema på den første konsultasjonen, under aborten og ved etterkontrollen 2-4 uker etter aborten. Under aborten rapporterte 66 % (296/450) moderat eller sterk smerte og 79 % (358/451) moderat eller sterk blødning. De fleste opplevde det som trygt å være hjemme. 96 % (390/406) ville valgt medikamentell abort hos avtalespesialist ved en eventuell senere abort, og 97 % (392/405) ville anbefalt behandlingstilbudet til andre i samme situasjon. Kvinnene i studien opplevde abortbehandling hos avtalespesialist som trygt. Tilbudet gir større valgfrihet til gravide som ønsker abort, og pasientene er tilfredse.

  12. A Tale of Tidal Tales in the Milky Way

    NASA Astrophysics Data System (ADS)

    Casey, Andrew R.

    2014-05-01

    Hundreds of globular clusters and dwarf galaxies encircle the Milky Way. Many of these systems have undergone partial disruption due to tidal forces, littering the halo with stellar streams. These tidal tails are sensitive to the Galactic potential, facilitating an excellent laboratory to investigate galaxy formation and evolution. To better understand the emergence of the Milky Way, this thesis examines the dynamics and chemistry of a number of known stellar streams. In particular the Sagittarius, Orphan and Aquarius streams are investigated. Low-resolution spectra for hundreds of stars in the direction of the Virgo Over-Density and the Sagittarius northern leading arms have been obtained. Multiple significant kinematic groups are recovered in this accretion-dominated region, confirming detections by previous studies. A metal-poor population ([Fe/H] = -1.7) in the Sagittarius stream is discovered due to a photometric selection that was inadvertently biased towards more metal-poor stars. Positions and kinematics of Sagittarius stream members are compared with existing best-fitting dark matter models, and a triaxial dark matter halo distribution is favoured. The Orphan stream is appropriately named, as no parent system has yet been identified. The stream has an extremely low surface brightness, which makes distinguishing stream members from field stars particularly challenging. From low-resolution spectra obtained for hundreds of stars, we identify likely Orphan stream red giant branch stars on the basis of velocity, metallicity, surface gravity, and proper motions. A negligible intrinsic velocity dispersion is found, and a wide spread in metallicities is observed, which suggests the undiscovered parent is similar to the present-day dwarf galaxies in the Milky Way. High-resolution spectra were obtained for five Orphan stream candidates, and the intrinsic chemical dispersion found from low-resolution spectra is confirmed from these data. Detailed chemical abundances for high-probability Orphan stream candidates further indicates a dwarf galaxy host. Low [α/Fe] abundance ratios are observed, and lower limits for [Ba/Y] are found, which sit well above the observed chemical evolution in the Milky Way. This thesis provides the first detailed chemical evidence for a dwarf galaxy origin, allowing us to rule out any association between the Orphan stream and the globular cluster NGC 2419. High-resolution, high S/N spectra for one third of the Aquarius stream have also been obtained. Contrary to previous work, there is no evidence that the Aquarius stream has resulted from a disrupted globular cluster. Detailed chemistry suggests that the Aquarius stars are galactic in origin, and not disrupted members from either a globular cluster or a dwarf galaxy. In the absence of compelling dynamic and/or chemical evidence to suggest otherwise, we advocate the 'Aquarius Group' as a more appropriate description, and hypothesise that the moving group has resulted from a disk-satellite interaction. The high-resolution spectra presented in this thesis has been analysed using custom written software, ironically named 'Spectroscopy Made Hard'. A detailed description of the software, capabilities and algorithms are presented. Spectroscopy Made Hard includes an intuitive graphical user interface, allowing the spectroscopist to interactively modify any aspect of their analysis. The software is designed to facilitate the transition between small and massive sample sizes, while ensuring data provenance, tangibility, and reproducibility. Future applications for this software are outlined, with a particular focus on the large scale high-resolution spectroscopic surveys being planned or currently undertaken.

  13. Evaluating the Claims of Network Centric Warfare

    DTIC Science & Technology

    2005-12-01

    judgments (see Bar- Tal , Raviv , & Spitzer, 1999). However, not everyone’s reactions to stressors are the same. A 12-month team performance study...45-58. Bar- Tal , Y. Raviv , A., & Spitzer, A. (1999). The need and ability to achieve cognitive structuring: Individual differences that moderate...definiteness, and regularity” (Bar- Tal , 1994, p. 45). Stress is one of the human responses to uncertainty. Stress can be initiated by a distinct event

  14. Development of a liposome microbicide formulation for vaginal delivery of octylglycerol for HIV prevention

    PubMed Central

    Wang, Lin; Sassi, Alexandra Beumer; Patton, Dorothy; Isaacs, Charles; Moncla, B. J.; Gupta, Phalguni; Rohan, Lisa Cencia

    2015-01-01

    The feasibility of using a liposome drug delivery system to formulate octylglycerol (OG) as a vaginal microbicide product was explored. A liposome formulation was developed containing 1% OG and phosphatidyl choline in a ratio that demonstrated in vitro activity against Neisseria gonorrhoeae, HSV-1, HSV-2 and HIV-1 while sparing the innate vaginal flora, Lactobacillus. Two conventional gel formulations were prepared for comparison. The OG liposome formulation with the appropriate OG/lipid ratio and dosing level had greater efficacy than either conventional gel formulation and maintained this efficacy for at least 2 months. No toxicity was observed for the liposome formulation in ex vivo testing in a human ectocervical tissue model or in vivo testing in the macaque safety model. Furthermore, minimal toxicity was observed to lactobacilli in vitro or in vivo safety testing. The OG liposome formulation offers a promising microbicide product with efficacy against HSV, HIV and N. gonorrhoeae. PMID:22149387

  15. Validation of the American Board of Orthodontics Objective Grading System for assessing the treatment outcomes of Chinese patients.

    PubMed

    Song, Guang-Ying; Baumrind, Sheldon; Zhao, Zhi-He; Ding, Yin; Bai, Yu-Xing; Wang, Lin; He, Hong; Shen, Gang; Li, Wei-Ran; Wu, Wei-Zi; Ren, Chong; Weng, Xuan-Rong; Geng, Zhi; Xu, Tian-Min

    2013-09-01

    Orthodontics in China has developed rapidly, but there is no standard index of treatment outcomes. We assessed the validity of the American Board of Orthodontics Objective Grading System (ABO-OGS) for the classification of treatment outcomes in Chinese patients. We randomly selected 108 patients who completed treatment between July 2005 and September 2008 in 6 orthodontic treatment centers across China. Sixty-nine experienced Chinese orthodontists made subjective assessments of the end-of-treatment casts for each patient. Three examiners then used the ABO-OGS to measure the casts. Pearson correlation analysis and receiver operating characteristic curve analysis were conducted to evaluate the correspondence between the ABO-OGS cast measurements and the orthodontists' subjective assessments. The average subjective grading scores were highly correlated with the ABO-OGS scores (r = 0.7042). Four of the 7 study cast components of the ABO-OGS score-occlusal relationship, overjet, interproximal contact, and alignment-were statistically significantly correlated with the judges' subjective assessments. Together, these 4 accounted for 58% of the variability in the average subjective grading scores. The ABO-OGS cutoff score for cases that the judges deemed satisfactory was 16 points; the corresponding cutoff score for cases that the judges considered acceptable was 21 points. The ABO-OGS is a valid index for the assessment of treatment outcomes in Chinese patients. By comparing the objective scores on this modification of the ABO-OGS with the mean subjective assessment of a panel of highly qualified Chinese orthodontists, a cutoff point for satisfactory treatment outcome was defined as 16 points or fewer, with scores of 16 to 21 points denoting less than satisfactory but still acceptable treatment. Cases that scored greater than 21 points were considered unacceptable. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  16. Distribution of the P2X2 receptor and chemical coding in ileal enteric neurons of obese male mice (ob/ob)

    PubMed Central

    Mizuno, Márcia Sanae; Crisma, Amanda Rabello; Borelli, Primavera; Schäfer, Bárbara Tavares; Silveira, Mariana Póvoa; Castelucci, Patricia

    2014-01-01

    AIM: To investigate the colocalization, density and profile of neuronal areas of enteric neurons in the ileum of male obese mice. METHODS: The small intestinal samples of male mice in an obese group (OG) (C57BL/6J ob/ob) and a control group (CG) (+/+) were used. The tissues were analyzed using a double immunostaining technique for immunoreactivity (ir) of the P2X2 receptor, nitric oxide synthase (NOS), choline acetyl transferase (ChAT) and calretinin (Calr). Also, we investigated the density and profile of neuronal areas of the NOS-, ChAT- and Calr-ir neurons in the myenteric plexus. Myenteric neurons were labeled using an NADH-diaphorase histochemical staining method. RESULTS: The analysis demonstrated that the P2X2 receptor was expressed in the cytoplasm and in the nuclear and cytoplasmic membranes only in the CG. Neuronal density values (neuron/cm2) decreased 31% (CG: 6579 ± 837; OG: 4556 ± 407) and 16.5% (CG: 7796 ± 528; OG: 6513 ± 610) in the NOS-ir and calretinin-ir neurons in the OG, respectively (P < 0.05). Density of ChAT-ir (CG: 6200 ± 310; OG: 8125 ± 749) neurons significantly increased 31% in the OG (P < 0.05). Neuron size studies demonstrated that NOS, ChAT, and Calr-ir neurons did not differ significantly between the CG and OG groups. The examination of NADH-diaphorase-positive myenteric neurons revealed an overall similarity between the OG and CG. CONCLUSION: Obesity may exert its effects by promoting a decrease in P2X2 receptor expression and modifications in the density of the NOS-ir, ChAT-ir and CalR-ir myenteric neurons. PMID:25320527

  17. Comparison of long-term results between laparoscopy-assisted gastrectomy and open gastrectomy with D2 lymph node dissection for advanced gastric cancer.

    PubMed

    Hamabe, Atsushi; Omori, Takeshi; Tanaka, Koji; Nishida, Toshirou

    2012-06-01

    Laparoscopy-assisted gastrectomy (LAG) has been established as a low-invasive surgery for early gastric cancer. However, it remains unknown whether it is applicable also for advanced gastric cancer, mainly because the long-term results of LAG with D2 lymph node dissection for advanced gastric cancer have not been well validated compared with open gastrectomy (OG). A retrospective cohort study was performed to compare LAG and OG with D2 lymph node dissection. For this study, 167 patients (66 LAG and 101 OG patients) who underwent gastrectomy with D2 lymph node dissection for advanced gastric cancer were reviewed. Recurrence-free survival and overall survival time were estimated using Kaplan-Meier curves. Stratified log-rank statistical evaluation was used to compare the difference between the LAG and OG groups stratified by histologic type, pathologic T status, N status, and postoperative adjuvant chemotherapy. The adjusted Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) of LAG. The 5-year recurrence-free survival rate was 89.6% in the LAG group and 75.8% in the OG group (nonsignificant difference; stratified log-rank statistic, 3.11; P = 0.0777). The adjusted HR of recurrence for LAG compared with OG was 0.389 [95% confidence interval (CI) 0.131-1.151]. The 5-year overall survival rate was 94.4% in the LAG group and 78.5% in the OG group (nonsignificant difference; stratified log-rank statistic, 0.4817; P = 0.4877). The adjusted HR of death for LAG compared with OG was 0.633 (95% CI 0.172-2.325). The findings show that LAG with D2 lymph node dissection is acceptable in terms of long-term results for advanced gastric cancer cases and may be applicable for advanced gastric cancer treatment.

  18. Oxygen Generator System Mars In-Situ Propellant Production Precursor Flight

    NASA Technical Reports Server (NTRS)

    Sridhar, K. R.; Gottmann, M.; Baird, R. S.

    1999-01-01

    The 2001 Lander to Mars will carry the first ever ISRU payload to Mars. This payload, the Mars In-situ Propellant production Precursor (MIP), will demonstrate a variety of technologies that will be required for future ISRU Mars indigenous material processing plant designs. One of those technologies is that of extracting oxygen from the predominantly carbon dioxide atmosphere of Mars, a prerequisite for future sample return and human missions to Mars. The Oxygen Generator Subsystem (OGS) portion of the MIP will demonstrate this and is the focus of this paper. The primary objective of the OGS is to demonstrate the production of oxygen from Mars atmospheric gases. Secondary objectives are to measure the performance and reliability of oxygen generation hardware in actual mission environments over an extended time. Major constraints on the OGS design came from several sources. The Lander provides power to the system from solar power that is harnessed by photovoltaic arrays. This limited OGS to daytime only operations (six to eight hours) and a maximum power of 15W. The reliance on solar power necessitated thermal cycling of the OGS between Mars ambient and OGS operating temperatures. The Lander also limited the total mass of the MIP payload to 7.5 kg with a correspondingly small volume, and the OGS was one of six experiments in the MIP. Mass and volume were to be minimized. Another constraint was cost. Mission funding, as always, was tight. Cost was to be minimized. In short the OGS design had to be low power (<15 Watts), low mass (1 kg), low volume, low cost, and be capable of cyclical operations for an extended stay on Mars. After extensive research, a zirconia based solid oxide electrolyzer design was selected.

  19. Oxygen Generator System Mars In-Situ Propellant Production Precursor Flight

    NASA Technical Reports Server (NTRS)

    Sridhar, K. R.; Gottmann, M.; Baird, R. S.

    1999-01-01

    The 2001 Lander to Mars will carry the first ever In situ Resource Utilization (ISRU) payload to Mars. This payload, the Mars In-situ Propellant production Precursor (MIP), will demonstrate a variety of technologies that will be required for future ISRU Mars indigenous material processing plant designs. One of those technologies is that of extracting oxygen from the predominantly carbon dioxide atmosphere of Mars, a prerequisite for future sample return and human missions to Mars. The Oxygen Generator Subsystem (OGS) portion of the MIP will demonstrate this and is the focus of this paper. The primary objective of the OGS is to demonstrate the production of oxygen from Mars atmospheric gases. Secondary objectives are to measure the performance and reliability of oxygen generation hardware in actual mission environments over an extended time. Major constraints on the OGS design came from several sources. The Lander provides power to the system from solar power that is harnessed by photovoltaic arrays. This limited OGS to daytime only operations (six to eight hours) and a maximum power of 15W. The reliance on solar power necessitated thermal cycling of the OGS between Mars ambient and OGS operating temperatures. The Lander also limited the total mass of the MIP payload to 7.5 kg with a correspondingly small volume, and the OGS was one of six experiments in the MIP Mass and volume were to be minimized. Another constraint was cost. Mission funding, as always, was tight. Cost was to be minimized. In short the OGS design had to be low power (<15 Watts), low mass (1 kg), low volume, low cost, and be capable of cyclical operations for an extended stay on Mars. After extensive research, a zirconia based solid oxide electrolyzer design was selected.

  20. Comparing Top-down and Bottom-up Estimates of Methane Emissions across Multiple U.S. Basins Provides Insights into National Oil and Gas Emissions and Mitigation Strategies

    NASA Astrophysics Data System (ADS)

    Hamburg, S.; Alvarez, R.; Lyon, D. R.; Zavala-Araiza, D.

    2016-12-01

    Several recent studies quantified regional methane emissions in U.S. oil and gas (O&G) basins using top-down approaches such as airborne mass balance measurements. These studies apportioned total methane emissions to O&G based on hydrocarbon ratios or subtracting bottom-up estimates of other sources. In most studies, top-down estimates of O&G methane emissions exceeded bottom-up emission inventories. An exception is the Barnett Shale Coordinated Campaign, which found agreement between aircraft mass balance estimates and a custom emission inventory. Reconciliation of Barnett Shale O&G emissions depended on two key features: 1) matching the spatial domains of top-down and bottom-up estimates, and 2) accounting for fat-tail sources in site-level emission factors. We construct spatially explicit custom emission inventories for domains with top-down O&G emission estimates in eight major U.S. oil and gas production basins using a variety of data sources including a spatially-allocated U.S. EPA Greenhouse Gas Inventory, the EPA Greenhouse Gas Reporting Program, state emission inventories, and recently published measurement studies. A comparison of top-down and our bottom-up estimates of O&G emissions constrains the gap between these approaches and elucidates regional variability in production-normalized loss rates. A comparison of component-level and site-level emission estimates of production sites in the Barnett Shale region - where comprehensive activity data and emissions estimates are available - indicates that abnormal process conditions contribute about 20% of regional O&G emissions. Combining these two analyses provides insights into the relative importance of different equipment, processes, and malfunctions to emissions in each basin. These data allow us to estimate the U.S. O&G supply chain loss rate, recommend mitigation strategies to reduce emissions from existing infrastructure, and discuss how a similar approach can be applied internationally.