Sample records for spliced leader trapping

  1. An in vivo genetic screen for genes involved in spliced leader trans-splicing indicates a crucial role for continuous de novo spliced leader RNP assembly. (United States)

    Philippe, Lucas; Pandarakalam, George C; Fasimoye, Rotimi; Harrison, Neale; Connolly, Bernadette; Pettitt, Jonathan; Müller, Berndt


    Spliced leader (SL) trans-splicing is a critical element of gene expression in a number of eukaryotic groups. This process is arguably best understood in nematodes, where biochemical and molecular studies in Caenorhabditis elegans and Ascaris suum have identified key steps and factors involved. Despite this, the precise details of SL trans-splicing have yet to be elucidated. In part, this is because the systematic identification of the molecules involved has not previously been possible due to the lack of a specific phenotype associated with defects in this process. We present here a novel GFP-based reporter assay that can monitor SL1 trans-splicing in living C. elegans. Using this assay, we have identified mutants in sna-1 that are defective in SL trans-splicing, and demonstrate that reducing function of SNA-1, SNA-2 and SUT-1, proteins that associate with SL1 RNA and related SmY RNAs, impairs SL trans-splicing. We further demonstrate that the Sm proteins and pICln, SMN and Gemin5, which are involved in small nuclear ribonucleoprotein assembly, have an important role in SL trans-splicing. Taken together these results provide the first in vivo evidence for proteins involved in SL trans-splicing, and indicate that continuous replacement of SL ribonucleoproteins consumed during trans-splicing reactions is essential for effective trans-splicing. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Leader-to-leader splicing is required for efficient production and accumulation of polyomavirus late mRNAs.


    Adami, G R; Marlor, C W; Barrett, N L; Carmichael, G G


    Polyomavirus late mRNA molecules contain multiple, tandem copies of a noncoding 57-base "late leader" exon at their 5' ends. This exon is encoded only once in the genome. Leader multiplicity arises from leader-leader splicing in giant primary transcripts, which are the result of multiple circuits of the viral genome by RNA polymerase II. We have been interested in learning more about the role of the leader exon in late viral gene expression. We recently showed that an abbreviated-leader mutan...

  3. Convergent origins and rapid evolution of spliced leader trans-splicing in metazoa: insights from the ctenophora and hydrozoa. (United States)

    Derelle, Romain; Momose, Tsuyoshi; Manuel, Michael; Da Silva, Corinne; Wincker, Patrick; Houliston, Evelyn


    Replacement of mRNA 5' UTR sequences by short sequences trans-spliced from specialized, noncoding, spliced leader (SL) RNAs is an enigmatic phenomenon, occurring in a set of distantly related animal groups including urochordates, nematodes, flatworms, and hydra, as well as in Euglenozoa and dinoflagellates. Whether SL trans-splicing has a common evolutionary origin and biological function among different organisms remains unclear. We have undertaken a systematic identification of SL exons in cDNA sequence data sets from non-bilaterian metazoan species and their closest unicellular relatives. SL exons were identified in ctenophores and in hydrozoan cnidarians, but not in other cnidarians, placozoans, or sponges, or in animal unicellular relatives. Mapping of SL absence/presence obtained from this and previous studies onto current phylogenetic trees favors an evolutionary scenario involving multiple origins for SLs during eumetazoan evolution rather than loss from a common ancestor. In both ctenophore and hydrozoan species, multiple SL sequences were identified, showing high sequence diversity. Detailed analysis of a large data set generated for the hydrozoan Clytia hemisphaerica revealed trans-splicing of given mRNAs by multiple alternative SLs. No evidence was found for a common identity of trans-spliced mRNAs between different hydrozoans. One feature found specifically to characterize SL-spliced mRNAs in hydrozoans, however, was a marked adenosine enrichment immediately 3' of the SL acceptor splice site. Our findings of high sequence divergence and apparently indiscriminate use of SLs in hydrozoans, along with recent findings in other taxa, indicate that SL genes have evolved rapidly in parallel in diverse animal groups, with constraint on SL exon sequence evolution being apparently rare.

  4. Footprints of a trypanosomatid RNA world: pre-small subunit rRNA processing by spliced leader addition trans-splicing

    Directory of Open Access Journals (Sweden)

    Mario Gustavo Mayer


    Full Text Available The addition of a capped mini-exon [spliced leader (SL] through trans-splicing is essential for the maturation of RNA polymerase (pol II-transcribed polycistronic pre-mRNAs in all members of the Trypanosomatidae family. This process is an inter-molecular splicing reaction that follows the same basic rules of cis-splicing reactions. In this study, we demonstrated that mini-exons were added to precursor ribosomal RNA (pre-rRNA are transcribed by RNA pol I, including the 5' external transcribed spacer (ETS region. Additionally, we detected the SL-5'ETS molecule using three distinct methods and located the acceptor site between two known 5'ETS rRNA processing sites (A' and A1 in four different trypanosomatids. Moreover, we detected a polyadenylated 5'ETS upstream of the trans-splicing acceptor site, which also occurs in pre-mRNA trans-splicing. After treatment with an indirect trans-splicing inhibitor (sinefungin, we observed SL-5'ETS decay. However, treatment with 5-fluorouracil (a precursor of RNA synthesis that inhibits the degradation of pre-rRNA led to the accumulation of SL-5'ETS, suggesting that the molecule may play a role in rRNA degradation. The detection of trans-splicing in these molecules may indicate broad RNA-joining properties, regardless of the polymerase used for transcription.

  5. A directed approach for the identification of transcripts harbouring the spliced leader sequence and the effect of trans-splicing knockdown in Schistosoma mansoni. (United States)

    Mourão, Marina de Moraes; Bitar, Mainá; Lobo, Francisco Pereira; Peconick, Ana Paula; Grynberg, Priscila; Prosdocimi, Francisco; Waisberg, Michael; Cerqueira, Gustavo Coutinho; Macedo, Andréa Mara; Machado, Carlos Renato; Yoshino, Timothy; Franco, Glória Regina


    Schistosomiasis is a major neglected tropical disease caused by trematodes from the genus Schistosoma. Because schistosomes exhibit a complex life cycle and numerous mechanisms for regulating gene expression, it is believed that spliced leader (SL) trans-splicing could play an important role in the biology of these parasites. The purpose of this study was to investigate the function of trans-splicing in Schistosoma mansoni through analysis of genes that may be regulated by this mechanism and via silencing SL-containing transcripts through RNA interference. Here, we report our analysis of SL transcript-enriched cDNA libraries from different S. mansoni life stages. Our results show that the trans-splicing mechanism is apparently not associated with specific genes, subcellular localisations or life stages. In cross-species comparisons, even though the sets of genes that are subject to SL trans-splicing regulation appear to differ between organisms, several commonly shared orthologues were observed. Knockdown of trans-spliced transcripts in sporocysts resulted in a systemic reduction of the expression levels of all tested trans-spliced transcripts; however, the only phenotypic effect observed was diminished larval size. Further studies involving the findings from this work will provide new insights into the role of trans-splicing in the biology of S. mansoni and other organisms. All Expressed Sequence Tags generated in this study were submitted to dbEST as five different libraries. The accessions for each library and for the individual sequences are as follows: (i) adult worms of mixed sexes (LIBEST_027999: JZ139310 - JZ139779), (ii) female adult worms (LIBEST_028000: JZ139780 - JZ140379), (iii) male adult worms (LIBEST_028001: JZ140380 - JZ141002), (iv) eggs (LIBEST_028002: JZ141003 - JZ141497) and (v) schistosomula (LIBEST_028003: JZ141498 - JZ141974).

  6. A directed approach for the identification of transcripts harbouring the spliced leader sequence and the effect of trans-splicing knockdown in Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Marina de Moraes Mourao


    Full Text Available Schistosomiasis is a major neglected tropical disease caused by trematodes from the genus Schistosoma. Because schistosomes exhibit a complex life cycle and numerous mechanisms for regulating gene expression, it is believed that spliced leader (SL trans-splicing could play an important role in the biology of these parasites. The purpose of this study was to investigate the function of trans-splicing in Schistosoma mansoni through analysis of genes that may be regulated by this mechanism and via silencing SL-containing transcripts through RNA interference. Here, we report our analysis of SL transcript-enriched cDNA libraries from different S. mansoni life stages. Our results show that the trans-splicing mechanism is apparently not associated with specific genes, subcellular localisations or life stages. In cross-species comparisons, even though the sets of genes that are subject to SL trans-splicing regulation appear to differ between organisms, several commonly shared orthologues were observed. Knockdown of trans-spliced transcripts in sporocysts resulted in a systemic reduction of the expression levels of all tested trans-spliced transcripts; however, the only phenotypic effect observed was diminished larval size. Further studies involving the findings from this work will provide new insights into the role of trans-splicing in the biology of S. mansoni and other organisms. All Expressed Sequence Tags generated in this study were submitted to dbEST as five different libraries. The accessions for each library and for the individual sequences are as follows: (i adult worms of mixed sexes (LIBEST_027999: JZ139310 - JZ139779, (ii female adult worms (LIBEST_028000: JZ139780 - JZ140379, (iii male adult worms (LIBEST_028001: JZ140380 - JZ141002, (iv eggs (LIBEST_028002: JZ141003 - JZ141497 and (v schistosomula (LIBEST_028003: JZ141498 - JZ141974.

  7. A Phylogenetic Survey on the Structure of the HIV-1 Leader RNA Domain That Encodes the Splice Donor Signal. (United States)

    Mueller, Nancy; Das, Atze T; Berkhout, Ben


    RNA splicing is a critical step in the human immunodeficiency virus type 1 (HIV-1) replication cycle because it controls the expression of the complex viral proteome. The major 5' splice site (5'ss) that is positioned in the untranslated leader of the HIV-1 RNA transcript is of particular interest because it is used for the production of the more than 40 differentially spliced subgenomic mRNAs. HIV-1 splicing needs to be balanced tightly to ensure the proper levels of all viral proteins, including the Gag-Pol proteins that are translated from the unspliced RNA. We previously presented evidence that the major 5'ss is regulated by a repressive local RNA structure, the splice donor (SD) hairpin, that masks the 11 nucleotides (nts) of the 5'ss signal for recognition by U1 small nuclear RNA (snRNA) of the spliceosome machinery. A strikingly different multiple-hairpin RNA conformation was recently proposed for this part of the HIV-1 leader RNA. We therefore inspected the sequence of natural HIV-1 isolates in search for support, in the form of base pair (bp) co-variations, for the different RNA conformations.

  8. Spliced leader RNA silencing (SLS - a programmed cell death pathway in Trypanosoma brucei that is induced upon ER stress

    Directory of Open Access Journals (Sweden)

    Michaeli Shulamit


    Full Text Available Abstract Trypanosoma brucei is the causative agent of African sleeping sickness. The parasite cycles between its insect (procyclic form and mammalian hosts (bloodstream form. Trypanosomes lack conventional transcription regulation, and their genes are transcribed in polycistronic units that are processed by trans-splicing and polyadenylation. In trans-splicing, which is essential for processing of each mRNA, an exon, the spliced leader (SL is added to all mRNAs from a small RNA, the SL RNA. Trypanosomes lack the machinery for the unfolded protein response (UPR, which in other eukaryotes is induced under endoplasmic reticulum (ER stress. Trypanosomes respond to such stress by changing the stability of mRNAs, which are essential for coping with the stress. However, under severe ER stress that is induced by blocking translocation of proteins to the ER, treatment of cells with chemicals that induce misfolding in the ER, or extreme pH, trypanosomes elicit the spliced leader silencing (SLS pathway. In SLS, the transcription of the SL RNA gene is extinguished, and tSNAP42, a specific SL RNA transcription factor, fails to bind to its cognate promoter. SLS leads to complete shut-off of trans-splicing. In this review, I discuss the UPR in mammals and compare it to the ER stress response in T. brucei leading to SLS. I summarize the evidence supporting the notion that SLS is a programmed cell death (PCD pathway that is utilized by the parasites to substitute for the apoptosis observed in higher eukaryotes under prolonged ER stress. I present the hypothesis that SLS evolved to expedite the death process, and rapidly remove from the population unfit parasites that, by elimination via SLS, cause minimal damage to the parasite population.

  9. Short leader sequences may be transferred from small RNAs to pre-mature mRNAs by trans-splicing in Euglena. (United States)

    Tessier, L H; Keller, M; Chan, R L; Fournier, R; Weil, J H; Imbault, P


    Very closely related short sequences are present at the 5' end of cytoplasmic mRNAs in Euglena as evidenced by comparison of cDNA sequences and hybrid-arrested translation experiments. By cloning Euglena gracilis nuclear DNA and isolating the rbcS gene (encoding the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase), we have shown that the short leader sequence does not flank the nuclear gene sequence. The leader sequences were found to constitute the 5' extremities of a family of small RNAs. Sequencing six members of this family revealed a striking similarity to vertebrate U snRNAs. We propose that a trans-splicing mechanism transfers the spliced leader (SL) sequence from these small RNAs (SL RNAs) to pre-mature mRNAs. Transfer of leader sequences to mRNAs by trans-splicing has been shown only in trypanosomes where cis-splicing is unknown, and in nematodes where not more than 10% of the mRNAs have leader sequences. Our results strongly suggest that Euglena is a unique organism in which both a widespread trans-splicing and a cis-splicing mechanism co-exist. Images PMID:1868836

  10. Persistent ER stress induces the spliced leader RNA silencing pathway (SLS, leading to programmed cell death in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Hanoch Goldshmidt


    Full Text Available Trypanosomes are parasites that cycle between the insect host (procyclic form and mammalian host (bloodstream form. These parasites lack conventional transcription regulation, including factors that induce the unfolded protein response (UPR. However, they possess a stress response mechanism, the spliced leader RNA silencing (SLS pathway. SLS elicits shut-off of spliced leader RNA (SL RNA transcription by perturbing the binding of the transcription factor tSNAP42 to its cognate promoter, thus eliminating trans-splicing of all mRNAs. Induction of endoplasmic reticulum (ER stress in procyclic trypanosomes elicits changes in the transcriptome similar to those induced by conventional UPR found in other eukaryotes. The mechanism of up-regulation under ER stress is dependent on differential stabilization of mRNAs. The transcriptome changes are accompanied by ER dilation and elevation in the ER chaperone, BiP. Prolonged ER stress induces SLS pathway. RNAi silencing of SEC63, a factor that participates in protein translocation across the ER membrane, or SEC61, the translocation channel, also induces SLS. Silencing of these genes or prolonged ER stress led to programmed cell death (PCD, evident by exposure of phosphatidyl serine, DNA laddering, increase in reactive oxygen species (ROS production, increase in cytoplasmic Ca(2+, and decrease in mitochondrial membrane potential, as well as typical morphological changes observed by transmission electron microscopy (TEM. ER stress response is also induced in the bloodstream form and if the stress persists it leads to SLS. We propose that prolonged ER stress induces SLS, which serves as a unique death pathway, replacing the conventional caspase-mediated PCD observed in higher eukaryotes.

  11. The nuclear RNA binding protein RBP33 influences mRNA and spliced leader RNA abundance in Trypanosoma brucei. (United States)

    Cirovic, Olivera; Trikin, Roman; Hoffmann, Anneliese; Doiron, Nicholas; Jakob, Martin; Ochsenreiter, Torsten


    RNA recognition motif (RRM) containing proteins are important regulators of gene expression in trypanosomes. Here we expand our current knowledge on the exclusively nuclear localized RRM domain containing protein RBP33 of Trypanosoma brucei. Overexpression of RBP33 leads to a quick growth arrest in G2/M in bloodstream form cells likely due to an overall mRNA- and spliced leader abundance decrease while the ribosomal RNAs remain unaffected. The recombinant RBP33 binds to poly(A) and random sequence RNA in vitro confirming its role as a RNA binding protein. Finally super-resolution microscopy detects RBP33 in small punctae throughout the nucleus and surrounding the nucleolus, however the signal is depleted inside the nucleolus. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The role of polymorphisms in the spliced leader addition domain in determining promoter activity in Brugia malayi. (United States)

    Bailey, Michelle; Chauhan, Chitra; Liu, Canhui; Unnasch, Thomas R


    Previous studies of Brugia malayi promoters have suggested that they are unusual in that they lack the CAAT or TATAA boxes that are often emblematic of eucaryotic core promoter domains. Instead, the region surrounding the spliced leader (SL) addition site appears to function as the core promoter domain in B. malayi. To test the hypothesis that polymorphisms in this SL addition domain are important determinants of promoter activity, a series of domain swap mutants were prepared replacing the SL addition domain of the B. malayi 13kDa large subunit ribosomal protein (BmRPL13) with those of other ribosomal protein (RP) promoters exhibiting a wide range of activities. These constructs were then tested for promoter activity in a homologous transient transfection system. On average, polymorphisms in the SL addition domain were found to be responsible for 80% of the variation in promoter activity exhibited by the RP promoters tested. Essentially all of this effect could be attributable to polymorphisms in the 10nt located directly upstream of the SL addition site. A comparison of the sequence of this domain to the promoter activity exhibited by the domain swap mutants suggested that promoter activity was related to the number of T residues present in the coding strand of the upstream domain. Confirming this, mutation of the upstream domain of the promoter of the BmRPS4 gene to a homogeneous stretch of 10 T residues resulted in a significant increase in promoter activity. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Proof that dinoflagellate spliced leader (DinoSL) is a useful hook for fishing dinoflagellate transcripts from mixed microbial samples: Symbiodinium kawagutii as a case study. (United States)

    Zhang, Huan; Zhuang, Yunyun; Gill, John; Lin, Senjie


    The ability to analyze dinoflagellate lineage-specific transcriptomes in the natural environment would be powerful for gaining understanding on how these organisms thrive in diverse environments and how they form harmful algal blooms and produce biotoxins. This can be made possible by lineage-specific mRNA markers such as the dinoflagellate-specific trans-spliced leader (DinoSL). By constructing and sequencing a 5'-cap selective full-length cDNA library for a monoculture of the coral reef endosymbiotic dinoflagellate Symbiodinium kawagutii and a DinoSL-based cDNA library for a mixture of S. kawagutii and other phytoplankton, we found DinoSL in essentially all full-length cDNAs in the 5'-cap selective library. We also discovered that the DinoSL-based library contained functionally diverse transcripts all belonging to dinoflagellates with no evidence of biases toward certain groups of functional genes. The results verified that DinoSL is specific to dinoflagellate mRNAs and is ubiquitous in the dinoflagellate transcriptomes. Annotation of the unigene dataset generated from the two libraries combined indicated high functional diversity of the transcriptome and revealed some biochemical pathways previously undocumented in Symbiodinium such as an mRNA splicing machinery potentially serving both cis- and trans-splicing. The protocol will be useful for transcriptomic studies of Symbiodinium in hospite and other dinoflagellates in natural environments. Copyright © 2013 Elsevier GmbH. All rights reserved.

  14. Transcriptome and proteome analyses and the role of atypical calpain protein and autophagy in the spliced leader silencing pathway in Trypanosoma brucei. (United States)

    Hope, Ronen; Egarmina, Katarina; Voloshin, Konstantin; Waldman Ben-Asher, Hiba; Carmi, Shai; Eliaz, Dror; Drori, Yaron; Michaeli, Shulamit


    Under persistent ER stress, Trypanosoma brucei parasites induce the spliced leader silencing (SLS) pathway. In SLS, transcription of the SL RNA gene, the SL donor to all mRNAs, is extinguished, arresting trans-splicing and leading to programmed cell death (PCD). In this study, we investigated the transcriptome following silencing of SEC63, a factor essential for protein translocation across the ER membrane, and whose silencing induces SLS. The proteome of SEC63-silenced cells was analyzed with an emphasis on SLS-specific alterations in protein expression, and modifications that do not directly result from perturbations in trans-splicing. One such protein identified is an atypical calpain SKCRP7.1/7.2. Co-silencing of SKCRP7.1/7.2 and SEC63 eliminated SLS induction due its role in translocating the PK3 kinase. This kinase initiates SLS by migrating to the nucleus and phosphorylating TRF4 leading to shut-off of SL RNA transcription. Thus, SKCRP7.1 is involved in SLS signaling and the accompanying PCD. The role of autophagy in SLS was also investigated; eliminating autophagy through VPS34 or ATG7 silencing demonstrated that autophagy is not essential for SLS induction, but is associated with PCD. Thus, this study identified factors that are used by the parasite to cope with ER stress and to induce SLS and PCD. © 2016 John Wiley & Sons Ltd.

  15. Trypanosoma brucei gambiense Spliced Leader RNA Is a More Specific Marker for Cure of Human African Trypanosomiasis Than T. b. gambiense DNA. (United States)

    Ilboudo, Hamidou; Camara, Oumou; Ravel, Sophie; Bucheton, Bruno; Lejon, Veerle; Camara, Mamadou; Kaboré, Jacques; Jamonneau, Vincent; Deborggraeve, Stijn


    To assess the efficacy of treatment for human African trypanosomiasis, accurate tests that can discriminate relapse from cure are needed. We report the first data that the spliced leader (SL) RNA is a more specific marker for cure of human African trypanosomiasis than parasite DNA. In blood samples obtained from 61 patients in whom human African trypanosomiasis was cured, SL RNA detection had specificities of 98.4%-100%, while DNA detection had a specificity of only 77%. Data from our proof-of-concept study show that SL RNA detection has high potential as a test of cure. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail:

  16. Trypanosoma cruzi I genotypes in different geographic regions and transmission cycles based on a microsatellite motif of the intergenic spacer of spliced leader genes✯ (United States)

    Cura, Carolina I.; Mejía-Jaramillo, Ana M.; Duffy, Tomás; Burgos, Juan M.; Rodriguero, Marcela; Cardinal, Marta V.; Kjos, Sonia; Gurgel-Gonçalves, Rodrigo; Blanchet, Denis; De Pablos, Luis M.; Tomasini, Nicolás; Silva, Alex Da; Russomando, Graciela; Cuba Cuba, Cesar A.; Aznar, Christine; Abate, Teresa; Levin, Mariano J.; Osuna, Antonio; Gürtler, Ricardo E.; Diosque, Patricio; Solari, Aldo; Triana-Chávez, Omar; Schijman, Alejandro G.


    The intergenic region of spliced-leader (SL-IR) genes from 105 Trypanosoma cruzi I (Tc I) infected biological samples, culture isolates and stocks from 11 endemic countries, from Argentina to the USA were characterised, allowing identification of 76 genotypes with 54 polymorphic sites from 123 aligned sequences. On the basis of the microsatellite motif proposed by Herrera et al. (2007) to define four haplotypes in Colombia, we could classify these genotypes into four distinct Tc I SL-IR groups, three corresponding to the former haplotypes Ia (11 genotypes), Ib (11 genotypes) and Id (35 genotypes); and one novel group, Ie (19 genotypes). Genotypes harboring the Tc Ic motif were not detected in our study. Tc Ia was associated with domestic cycles in southern and northern South America and sylvatic cycles in Central and North America. Tc Ib was found in all transmission cycles from Colombia. Tc Id was identified in all transmission cycles from Argentina and Colombia, including Chagas cardiomyopathy patients, sylvatic Brazilian samples and human cases from French Guiana, Panama and Venezuela. Tc Ie gathered five samples from domestic Triatoma infestans from northern Argentina, nine samples from wild Mepraia spinolai and Mepraia gajardoi and two chagasic patients from Chile and one from a Bolivian patient with chagasic reactivation. Mixed infections by Tc Ia + Tc Id, Tc Ia + Tc Ie and Tc Id + Tc Ie were detected in vector faeces and isolates from human and vector samples. In addition, Tc Ia and Tc Id were identified in different tissues from a heart transplanted Chagas cardiomyopathy patient with reactivation, denoting histotropism. Trypanosoma cruzi I SL-IR genotypes from parasites infecting Triatoma gerstaeckeri and Didelphis virginiana from USA, T. infestans from Paraguay, Rhodnius nasutus and Rhodnius neglectus from Brazil and M. spinolai and M. gajardoi from Chile are to our knowledge described for the first time. PMID:20670628

  17. HIV-1 splicing at the major splice donor site is restricted by RNA structure. (United States)

    Mueller, Nancy; van Bel, Nikki; Berkhout, Ben; Das, Atze T


    The 5' leader region of the HIV-1 RNA contains the major 5' splice site (ss) that is used in the production of all spliced viral RNAs. This splice-donor (SD) region can fold a stem-loop structure. We demonstrate that whereas stabilization of this SD hairpin reduces splicing efficiency, destabilization increases splicing. Both stabilization and destabilization reduce viral fitness. These results demonstrate that the stability of the SD hairpin can modulate the level of splicing, most likely by controlling the accessibility of the 5'ss for the splicing machinery. The natural stability of the SD hairpin restricts splicing and this stability seems to be fine-tuned to reach the optimal balance between unspliced and spliced RNAs for efficient virus replication. The 5'ss region of different HIV-1 isolates and the related SIVmac239 can fold a similar structure. This evolutionary conservation supports the importance of this structure in viral replication. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. The Trypanosoma brucei La protein is a candidate poly(U) shield that impacts spliced leader RNA maturation and tRNA intron removal

    Czech Academy of Sciences Publication Activity Database

    Trantírková, Silvie; Paris, Zdeněk; Sturm, N. R.; Campbell, D. A.; Lukeš, Julius


    Roč. 35, č. 4 (2005), s. 359-366 ISSN 0020-7519 R&D Projects: GA AV ČR IAA5022302 Grant - others:NIH(US) AI34536; NIH(US) AI056034 Institutional research plan: CEZ:AV0Z60220518 Keywords : splicing * Trypanosoma * RNA interference Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.346, year: 2005

  19. Gene trap mutagenesis of hnRNP A2/B1: a cryptic 3' splice site in the neomycin resistance gene allows continued expression of the disrupted cellular gene

    Directory of Open Access Journals (Sweden)

    DeGregori James V


    Full Text Available Abstract Background Tagged sequence mutagenesis is a process for constructing libraries of sequenced insertion mutations in embryonic stem cells that can be transmitted into the mouse germline. To better predict the functional consequences of gene entrapment on cellular gene expression, the present study characterized the effects of a U3Neo gene trap retrovirus inserted into an intron of the hnRNP A2/B1 gene. The mutation was selected for analysis because it occurred in a highly expressed gene and yet did not produce obvious phenotypes following germline transmission. Results Sequences flanking the integrated gene trap vector in 1B4 cells were used to isolate a full-length cDNA whose predicted amino acid sequence is identical to the human A2 protein at all but one of 341 amino acid residues. hnRNP A2/B1 transcripts extending into the provirus utilize a cryptic 3' splice site located 28 nucleotides downstream of the neomycin phosphotransferase start codon. The inserted Neo sequence and proviral poly(A site function as an 3' terminal exon that is utilized to produce hnRNP A2/B1-Neo fusion transcripts, or skipped to produce wild-type hnRNP A2/B1 transcripts. This results in only a modest disruption of hnRNPA2/B1 gene expression. Conclusions Expression of the occupied hnRNP A2/B1 gene and utilization of the viral poly(A site are consistent with an exon definition model of pre-mRNA splicing. These results reveal a mechanism by which U3 gene trap vectors can be expressed without disrupting cellular gene expression, thus suggesting ways to improve these vectors for gene trap mutagenesis.

  20. Reversion of the Arabidopsis rpn12a-1 exon-trap mutation by an intragenic suppressor that weakens the chimeric 5’ splice site [v2; ref status: indexed,

    Directory of Open Access Journals (Sweden)

    Jasmina Kurepa


    Full Text Available Background: In the Arabidopsis 26S proteasome mutant rpn12a-1, an exon-trap T-DNA is inserted 531 base pairs downstream of the RPN12a STOP codon. We have previously shown that this insertion activates a STOP codon-associated latent 5' splice site that competes with the polyadenylation signal during processing of the pre-mRNA. As a result of this dual input from splicing and polyadenylation in the rpn12a-1 mutant, two RPN12a transcripts are produced and they encode the wild-type RPN12a and a chimeric RPN12a-NPTII protein. Both proteins form complexes with other proteasome subunits leading to the formation of wild-type and mutant proteasome versions. The net result of this heterogeneity of proteasome particles is a reduction of total cellular proteasome activity. One of the consequences of reduced proteasomal activity is decreased sensitivity to the major plant hormone cytokinin. Methods: We performed ethyl methanesulfonate mutagenesis of rpn12a-1 and isolated revertants with wild-type cytokinin sensitivity. Results: We describe the isolation and analyses of suppressor of rpn12a-1 (sor1. The sor1 mutation is intragenic and located at the fifth position of the chimeric intron. This mutation weakens the activated 5' splice site associated with the STOP codon and tilts the processing of the RPN12a mRNA back towards polyadenylation. Conclusions: These results validate our earlier interpretation of the unusual nature of the rpn12a-1 mutation. Furthermore, the data show that optimal 26S proteasome activity requires RPN12a accumulation beyond a critical threshold. Finally, this finding reinforces our previous conclusion that proteasome function is critical for the cytokinin-dependent regulation of plant growth.

  1. The identification of two Trypanosoma cruzi I genotypes from domestic and sylvatic transmission cycles in Colombia based on a single polymerase chain reaction amplification of the spliced-leader intergenic region

    Directory of Open Access Journals (Sweden)

    Lina Marcela Villa


    Full Text Available A single polymerase chain reaction (PCR reaction targeting the spliced-leader intergenic region of Trypanosoma cruzi I was standardised by amplifying a 231 bp fragment in domestic (TcIDOM strains or clones and 450 and 550 bp fragments in sylvatic strains or clones. This reaction was validated using 44 blind coded samples and 184 non-coded T. cruzi I clones isolated from sylvatic triatomines and the correspondence between the amplified fragments and their domestic or sylvatic origin was determined. Six of the nine strains isolated from acute cases suspected of oral infection had the sylvatic T. cruzi I profile. These results confirmed that the sylvatic T. cruzi I genotype is linked to cases of oral Chagas disease in Colombia. We therefore propose the use of this novel PCR reaction in strains or clones previously characterised as T. cruzi I to distinguish TcIDOMfrom sylvatic genotypes in studies of transmission dynamics, including the verification of population selection within hosts or detection of the frequency of mixed infections by both T. cruzi I genotypes in Colombia.

  2. tRNA splicing


    Abelson, John; Trotta, Christopher R.; Li, Hong


    Introns interrupt the continuity of many eukaryal genes, and therefore their removal by splicing is a crucial step in gene expression. Interestingly, even within Eukarya there are at least four splicing mechanisms. mRNA splicing in the nucleus takes place in two phosphotransfer reactions on a complex and dynamic machine, the spliceosome. This reaction is related in mechanism to the two self-splicing mechanisms for Group 1 and Group 2 introns. In fact the Group 2 introns are spliced by an iden...

  3. spliceR

    DEFF Research Database (Denmark)

    Vitting-Seerup, Kristoffer; Porse, Bo Torben; Sandelin, Albin


    RNA-seq data is currently underutilized, in part because it is difficult to predict the functional impact of alternate transcription events. Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing...

  4. Multiset splicing systems. (United States)

    Dassow, Jürgen; Vaszil, György


    We consider splicing systems reflecting two important aspects of the behaviour of DNA molecules in nature or in laboratory experiments which so far have not been studied in the literature. We examine the effect of splicing rules applied to finite multisets of words using sequential and different types of parallel derivation strategies and compare the sets of words or sets of multisets which can be obtained.

  5. The neurogenetics of alternative splicing. (United States)

    Vuong, Celine K; Black, Douglas L; Zheng, Sika


    Alternative precursor-mRNA splicing is a key mechanism for regulating gene expression in mammals and is controlled by specialized RNA-binding proteins. The misregulation of splicing is implicated in multiple neurological disorders. We describe recent mouse genetic studies of alternative splicing that reveal its critical role in both neuronal development and the function of mature neurons. We discuss the challenges in understanding the extensive genetic programmes controlled by proteins that regulate splicing, both during development and in the adult brain.

  6. Alternative Splicing in Lung Cancer


    Pio, Ruben; Montuenga, Luis M.


    Abstract: Alterations in alternative splicing affect essential biologic processes and are the basis for a number of pathologic conditions, including cancer. In this review we will summarize the evidence supporting the relevance of alternative splicing in lung cancer. An example that illustrates this relevance is the altered balance between Bcl-xL and Bcl-xS, two splice variants of the apoptosis regulator Bcl-x. Splice modifications in cancer-related genes can be associated ...

  7. Regulation of HIV-1 splicing

    NARCIS (Netherlands)

    Müller, N.


    Human immunodeficiency virus type-1 (HIV-1) produces a single primary RNA transcript. The full-length transcript functions as RNA genome that is packaged into virions and as mRNA for translation of the Gag and Pol proteins. HIV-1 RNA contains several splice donor (5’splice site; 5’ss) and splice

  8. Where splicing joins chromatin

    Czech Academy of Sciences Publication Activity Database

    Hnilicová, Jarmila; Staněk, David


    Roč. 2, č. 3 (2011), s. 182-188 ISSN 1949-1034 R&D Projects: GA ČR GAP305/10/0424; GA AV ČR KAN200520801 Institutional research plan: CEZ:AV0Z50520514 Keywords : chromatin * exon * alternative splicing * transcription * snRNP Subject RIV: EB - Genetics ; Molecular Biology

  9. Expressiveness of basic Splice

    NARCIS (Netherlands)

    J.C. van de Pol (Jaco)


    textabstractWe study a simple software architecture, in which application processes are coordinated by writing into and reading from a global set. This architecture underlies Splice, which is developed and used at the company Hollandse Signaalapparaten. Our approach is distinguished by viewing the

  10. Alternative REST Splicing Underappreciated


    Chen, Guo-Lin; Miller, Gregory


    As a major orchestrator of the cellular epigenome, the repressor element-1 silencing transcription factor (REST) can either repress or activate thousands of genes depending on cellular context, suggesting a highly context-dependent REST function tuned by environmental cues. While REST shows cell-type non-selective active transcription, an N-terminal REST4 isoform caused by alternative splicing - inclusion of an extra exon (N3c) which introduces a pre-mature stop codon - has been implicated in...

  11. The neurogenetics of alternative splicing


    Vuong, Celine K.; Black, Douglas L.; Zheng, Sika


    Alternative precursor-mRNA splicing is a key mechanism for regulating gene expression in mammals and is controlled by specialized RNA-binding proteins. The misregulation of splicing is implicated in multiple neurological disorders. We describe recent mouse genetic studies of alternative splicing that reveal its critical role in both neuronal development and the function of mature neurons. We discuss the challenges in understanding the extensive genetic programmes controlled by proteins that r...

  12. Work organization for splice consolidation

    CERN Document Server

    Bertinelli, F


    The Splices Task Force has worked in 2010 to prepare the necessary interventions for 7 TeV operation. The design solution for consolidating the main interconnection splices is well advanced. The required activities to implement it are described, highlighting working assumptions, missing resources and schedule considerations. Progress has also been made in assessing other splices, 6 kA praying hands and corrector circuits: results and ongoing work are presented, highlighting priorities for the remaining work.

  13. Novel mutations affecting LRP5 splicing in patients with osteoporosis-pseudoglioma syndrome (OPPG). (United States)

    Laine, C M; Chung, B D; Susic, M; Prescott, T; Semler, O; Fiskerstrand, T; D'Eufemia, P; Castori, M; Pekkinen, M; Sochett, E; Cole, W G; Netzer, C; Mäkitie, O


    Osteoporosis-pseudoglioma sydrome (OPPG) is an autosomal recessive disorder with early-onset severe osteoporosis and blindness, caused by biallelic loss-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. Heterozygous carriers exhibit a milder bone phenotype. Only a few splice mutations in LRP5 have been published. We present clinical and genetic data for four patients with novel LRP5 mutations, three of which affect splicing. Patients were evaluated clinically and by radiography and bone densitometry. Genetic screening of LRP5 was performed on the basis of the clinical diagnosis of OPPG. Splice aberrances were confirmed by cDNA sequencing or exon trapping. The effect of one splice mutation on LRP5 protein function was studied. A novel splice-site mutation c.1584+4A>T abolished the donor splice site of exon 7 and activated a cryptic splice site, which led to an in-frame insertion of 21 amino acids (p.E528_V529ins21). Functional studies revealed severely impaired signal transduction presumably caused by defective intracellular transport of the mutated receptor. Exon trapping was used on two samples to confirm that splice-site mutations c.4112-2A>G and c.1015+1G>T caused splicing-out of exons 20 and 5, respectively. One patient carried a homozygous deletion of exon 4 causing the loss of exons 4 and 5, as demonstrated by cDNA analysis. Our results broaden the spectrum of mutations in LRP5 and provide the first functional data on splice aberrations.

  14. LEADER 2

    DEFF Research Database (Denmark)

    Daniels, G H; Hegedüs, L; Marso, S P


    AIMS: To report preliminary data on baseline serum calcitonin concentrations and associated clinical characteristics in a global population with type 2 diabetes before liraglutide or placebo randomization. METHODS: The ongoing LEADER trial has enrolled 9340 people with type 2 diabetes and at high...... committee of thyroid experts will oversee calcitonin monitoring throughout the trial and will review all calcitonin concentrations ≥20 ng/l. RESULTS: The mean age of participants was 64.3 ± 7.2 years, 64.3% were men, and mean the body mass index was 32.5 ± 6.3 kg/m(2) . The median (interquartile range...... with higher serum calcitonin concentrations that were statistically significant. A 20 ml/min/1.73 m(2) decrease in estimated GFR (eGFR) was associated with a 14% increase in serum calcitonin in women and an 11% increase in men. CONCLUSIONS: In the LEADER population, the prevalence of elevated serum calcitonin...

  15. Intronic Alus influence alternative splicing.

    Directory of Open Access Journals (Sweden)

    Galit Lev-Maor


    Full Text Available Examination of the human transcriptome reveals higher levels of RNA editing than in any other organism tested to date. This is indicative of extensive double-stranded RNA (dsRNA formation within the human transcriptome. Most of the editing sites are located in the primate-specific retrotransposed element called Alu. A large fraction of Alus are found in intronic sequences, implying extensive Alu-Alu dsRNA formation in mRNA precursors. Yet, the effect of these intronic Alus on splicing of the flanking exons is largely unknown. Here, we show that more Alus flank alternatively spliced exons than constitutively spliced ones; this is especially notable for those exons that have changed their mode of splicing from constitutive to alternative during human evolution. This implies that Alu insertions may change the mode of splicing of the flanking exons. Indeed, we demonstrate experimentally that two Alu elements that were inserted into an intron in opposite orientation undergo base-pairing, as evident by RNA editing, and affect the splicing patterns of a downstream exon, shifting it from constitutive to alternative. Our results indicate the importance of intronic Alus in influencing the splicing of flanking exons, further emphasizing the role of Alus in shaping of the human transcriptome.

  16. COLD TRAPS (United States)

    Thompson, W.I.


    A cold trap is presented for removing a condensable component from a gas mixture by cooling. It consists of a shell, the exterior surface of which is chilled by a refrigerant, and conductive fins welded inside the shell to condense the gas, and distribute the condensate evenly throughout the length of the trap, so that the trap may function until it becomes completely filled with the condensed solid. The contents may then be removed as either a gas or as a liquid by heating the trap. This device has particuinr use as a means for removing uranium hexafluoride from the gaseous diffusion separation process during equipment breakdown and repair periods.

  17. Handbook of knotting and splicing

    CERN Document Server

    Hasluck, Paul N


    Clearly written and amply illustrated with 208 figures, this classic guide ranges from simple and useful knots to complex varieties. Additional topics include rope splicing, working cordage, hammock making, more.

  18. Persuasion: A Leader's Edge

    National Research Council Canada - National Science Library

    McGuire, Mark


    .... Nevertheless, today's leaders should realize the need for persuasion. In one manner or another, leaders depend on persuasive rhetoric to convince, encourage, and energize superiors, peers, and subordinates...

  19. The uncompromising leader. (United States)

    Eisenstat, Russell A; Beer, Michael; Foote, Nathaniel; Fredberg, Tobias; Norrgren, Flemming


    Managing the tension between performance and people is at the heart of the CEO's job. But CEOs under fierce pressure from capital markets often focus solely on the shareholder, which can lead to employee disenchantment. Others put so much stock in their firms' heritage that they don't notice as their organizations slide into complacency. Some leaders, though, manage to avoid those traps and create high-commitment, high-performance (HCHP) companies. The authors' in-depth research of HCHP CEOs reveals several shared traits: These CEOs earn the trust of their organizations through their openness to the unvarnished truth. They are deeply engaged with their people, and their exchanges are direct and personal. They mobilize employees around a focused agenda, concentrating on only one or two initiatives. And they work to build collective leadership capabilities. These leaders also forge an emotionally resonant shared purpose across their companies. That consists of a three-part promise: The company will help employees build a better world and deliver performance they can be proud of, and will provide an environment in which they can grow. HCHP CEOs approach finding a firm's moral and strategic center in a competitive market as a calling, not an engineering problem. They drive their firms to be strongly market focused while at the same time reinforcing their firms' core values. They are committed to short-term performance while also investing in long-term leadership and organizational capabilities. By refusing to compromise on any of these terms, they build great companies.

  20. Exploring strategies for protein trapping in Drosophila

    Energy Technology Data Exchange (ETDEWEB)

    Quinones-Coello, Ana T.; Petrella, Lisa N.; Ayers, Kathleen; Melillo, Anthony; Mazzalupo, Stacy; Hudson, Andrew M.; Wang, Shu; Castiblanco, Claudia; Buszczak, Michael; Hoskins, Roger A.; Cooley, Lynn


    The use of fluorescent protein tags has had a huge impact oncell biological studies in virtually every experimental system.Incorporation of coding sequence for fluorescent proteins such as greenfluorescent protein (GFP) into genes at their endogenous chromosomalposition is especially useful for generating GFP-fusion proteins thatprovide accurate cellular and subcellular expression data. We testedmodifications of a transposon-based protein trap screening procedure inDrosophila to optimize the rate of recovering useful protein traps andtheir analysis. Transposons carrying the GFP-coding sequence flanked bysplice acceptor and donor sequences were mobilized, and new insertionsthat resulted in production of GFP were captured using an automatedembryo sorter. Individual stocks were established, GFP expression wasanalyzed during oogenesis, and insertion sites were determined bysequencing genomic DNA flanking the insertions. The resulting collectionincludes lines with protein traps in which GFP was spliced into mRNAs andembedded within endogenous proteins or enhancer traps in which GFPexpression depended on splicing into transposon-derived RNA. We report atotal of 335 genes associated with protein or enhancer traps and aweb-accessible database for viewing molecular information and expressiondata for these genes.

  1. 0-6652 : spliced Texas girder bridges. (United States)


    Spliced girder technology continues to attract : attention due to its versatility over traditional : prestressed concrete highway bridge construction. : By joining multiple precast concrete girders using : post-tensioning, spliced girder technology :...

  2. Neomycin B inhibits splicing of the td intron indirectly by interfering with translation and enhances missplicing in vivo. (United States)

    Waldsich, C; Semrad, K; Schroeder, R


    The aminoglycoside antibiotic neomycin B inhibits translation in prokaryotes and interferes with RNA-protein interactions in HIV both in vivo and in vitro. Hitherto, inhibition of ribozyme catalysis has only been observed in vitro. We therefore monitored the activity of neomycin B and several other aminoglycoside antibiotics on splicing of the T4 phage thymidylate synthase (td) intron in vivo. All antibiotics tested inhibited splicing, even chloramphenicol, which does not inhibit splicing in vitro. Splicing of the td intron in vivo requires translation for proper folding of the pre-mRNA. In the absence of translation, two interactions between sequences in the upstream exon and the 5' and 3' splice sites trap the pre-mRNA in splicing-incompetent conformations. Their disruption by mutations rendered splicing less dependent on translation and also less sensitive to neomycin B. Intron splicing was affected by neither neomycin B nor gentamicin in Escherichia coli strains carrying antibiotic-resistance genes that modify the ribosomal RNA. Taken together, this demonstrates that in vivo splicing of td intron is not directly inhibited by aminoglycosides, but rather indirectly by their interference with translation. This was further confirmed by assaying splicing of the Tetrahymena group I intron, which is inserted in the E. coli 23 S rRNA and, thus, not translated. Furthermore, neomycin B, paromomycin, and streptomycin enhanced missplicing in antibiotic-sensitive strains. Missplicing is caused by an alternative structural element containing a cryptic 5' splice site, which serves as a substrate for the ribozyme. Our results demonstrate that aminoglycoside antibiotics display different effects on ribozymes in vivo and in vitro.

  3. GC content around splice sites affects splicing through pre-mRNA secondary structures

    Directory of Open Access Journals (Sweden)

    Chen Liang


    Full Text Available Abstract Background Alternative splicing increases protein diversity by generating multiple transcript isoforms from a single gene through different combinations of exons or through different selections of splice sites. It has been reported that RNA secondary structures are involved in alternative splicing. Here we perform a genomic study of RNA secondary structures around splice sites in humans (Homo sapiens, mice (Mus musculus, fruit flies (Drosophila melanogaster, and nematodes (Caenorhabditis elegans to further investigate this phenomenon. Results We observe that GC content around splice sites is closely associated with the splice site usage in multiple species. RNA secondary structure is the possible explanation, because the structural stability difference among alternative splice sites, constitutive splice sites, and skipped splice sites can be explained by the GC content difference. Alternative splice sites tend to be GC-enriched and exhibit more stable RNA secondary structures in all of the considered species. In humans and mice, splice sites of first exons and long exons tend to be GC-enriched and hence form more stable structures, indicating the special role of RNA secondary structures in promoter proximal splicing events and the splicing of long exons. In addition, GC-enriched exon-intron junctions tend to be overrepresented in tissue-specific alternative splice sites, indicating the functional consequence of the GC effect. Compared with regions far from splice sites and decoy splice sites, real splice sites are GC-enriched. We also found that the GC-content effect is much stronger than the nucleotide-order effect to form stable secondary structures. Conclusion All of these results indicate that GC content is related to splice site usage and it may mediate the splicing process through RNA secondary structures.

  4. Leaders of the profession and 'professional' leaders

    DEFF Research Database (Denmark)

    Bøje, Jakob Ditlev; Frederiksen, Lars Frode

    of the professional complex according to a Parsonian perspective) and a more distinct leader identity associated with business, management, and accountancy. We will attempt to go beyond some of the manifest expectations of school leaders, including expectations of their training programmes, and show how being...

  5. Titin Diversity—Alternative Splicing Gone Wild

    Directory of Open Access Journals (Sweden)

    Wei Guo


    Full Text Available Titin is an extremely large protein found in highest concentrations in heart and skeletal muscle. The single mammalian gene is expressed in multiple isoforms as a result of alternative splicing. Although titin isoform expression is controlled developmentally and in a tissue specific manner, the vast number of potential splicing pathways far exceeds those described in any other alternatively spliced gene. Over 1 million human splice pathways for a single individual can be potentially derived from the PEVK region alone. A new splicing pattern for the human cardiac N2BA isoform type has been found in which the PEVK region includes only the N2B type exons. The alterations in splicing and titin isoform expression in human heart disease provide impetus for future detailed study of the splicing mechanisms for this giant protein.

  6. Jesus the Strategic Leader

    National Research Council Canada - National Science Library

    Martin, Gregg


    Jesus was a great strategic leader who changed the world in many ways. Close study of what he did and how he did it reveals a pattern of behavior that is extremely useful and relevant to the modern strategic leader...

  7. Elementary Mathematics Leaders (United States)

    Fennell, Francis; Kobett, Beth McCord; Wray, Jonathan A.


    Elementary school mathematics leaders often come to the realization that their position, however titled and determined, although dedicated to addressing needs in math teaching and learning, also entails and directly involves leadership. Elementary school math specialists/instructional leaders (referenced here as elementary mathematics leaders, or…

  8. The Resilient Leader (United States)

    Allison, Elle


    School leaders currently face so many challenges--some as basic as a lack of money to hire enough teachers--that they know they need to increase their resilience. According to Allison, who coaches school leaders, strong leaders know how important maintaining resilience is. They recognize when their reserves of hope--and those of their…

  9. Trapped antihydrogen

    CERN Document Server

    Butler, E; Ashkezari, M D; Baquero-Ruiz, M; Bertsche, W; Bowe, P D; Cesar, C L; Chapman, S; Charlton, M; Deller, A; Eriksson, S; Fajans, J; Friesen, T; Fujiwara, M C; Gill, D R; Gutierrez, A; Hangst, J S; Hardy, W N; Hayden, M E; Humphries, A J; Hydomako, R; Jenkins, M J; Jonsell, S; Jørgensen, L V; Kemp, S L; Kurchaninov, L; Madsen, N; Menary, S; Nolan, P; Olchanski, K; Olin, A; Povilus, A; Pusa, P; Rasmussen, C Ø; Robicheaux, F; Sarid, E; Seif el Nasr, S; Silveira, D M; So, C; Storey, J W; Thompson, R I; van der Werf, D P; Wurtele, J S; Yamazaki,Y


    Precision spectroscopic comparison of hydrogen and antihydrogen holds the promise of a sensitive test of the Charge-Parity-Time theorem and matter-antimatter equivalence. The clearest path towards realising this goal is to hold a sample of antihydrogen in an atomic trap for interrogation by electromagnetic radiation. Achieving this poses a huge experimental challenge, as state-of-the-art magnetic-minimum atom traps have well depths of only ∼1 T (∼0.5 K for ground state antihydrogen atoms). The atoms annihilate on contact with matter and must be ‘born’ inside the magnetic trap with low kinetic energies. At the ALPHA experiment, antihydrogen atoms are produced from antiprotons and positrons stored in the form of non-neutral plasmas, where the typical electrostatic potential energy per particle is on the order of electronvolts, more than 104 times the maximum trappable kinetic energy. In November 2010, ALPHA published the observation of 38 antiproton annihilations due to antihydrogen atoms that had been ...

  10. Alternative Splicing in Plant Immunity

    Directory of Open Access Journals (Sweden)

    Shengming Yang


    Full Text Available Alternative splicing (AS occurs widely in plants and can provide the main source of transcriptome and proteome diversity in an organism. AS functions in a range of physiological processes, including plant disease resistance, but its biological roles and functional mechanisms remain poorly understood. Many plant disease resistance (R genes undergo AS, and several R genes require alternatively spliced transcripts to produce R proteins that can specifically recognize pathogen invasion. In the finely-tuned process of R protein activation, the truncated isoforms generated by AS may participate in plant disease resistance either by suppressing the negative regulation of initiation of immunity, or by directly engaging in effector-triggered signaling. Although emerging research has shown the functional significance of AS in plant biotic stress responses, many aspects of this topic remain to be understood. Several interesting issues surrounding the AS of R genes, especially regarding its functional roles and regulation, will require innovative techniques and additional research to unravel.

  11. VACUUM TRAP (United States)

    Gordon, H.S.


    An improved adsorption vacuum trap for use in vacuum systems was designed. The distinguishing feature is the placement of a plurality of torsionally deformed metallic fins within a vacuum jacket extending from the walls to the central axis so that substantially all gas molecules pass through the jacket will impinge upon the fin surfaces. T fins are heated by direct metallic conduction, thereby ol taining a uniform temperature at the adeorbing surfaces so that essentially all of the condensible impurities from the evacuating gas are removed from the vacuum system.

  12. Capacity of columns with splice imperfections

    International Nuclear Information System (INIS)

    Popov, E.P.; Stephen, R.M.


    To study the behavior of spliced columns subjected to tensile forces simulating situations which may develop in an earthquake, all of the spliced specimens were tested to failure in tension after first having been subjected to large compressive loads. The results of these tests indicate that the lack of perfect contact at compression splices of columns may not be important, provided that the gaps are shimmed and welding is used to maintain the sections in alignment

  13. The connection between splicing and cancer


    Srebrow, Anabella; Kornblihtt, Alberto Rodolfo


    Alternative splicing is a crucial mechanism for generating protein diversity. Different splice variants of a given protein can display different and even antagonistic biological functions. Therefore, appropriate control of their synthesis is required to assure the complex orchestration of cellular processes within multicellular organisms. Mutations in cisacting splicing elements or changes in the activity of regulatory proteins that compromise the accuracy of either constitutive or alternativ...

  14. Alternative Splicing in Neurogenesis and Brain Development

    Directory of Open Access Journals (Sweden)

    Chun-Hao Su


    Full Text Available Alternative splicing of precursor mRNA is an important mechanism that increases transcriptomic and proteomic diversity and also post-transcriptionally regulates mRNA levels. Alternative splicing occurs at high frequency in brain tissues and contributes to every step of nervous system development, including cell-fate decisions, neuronal migration, axon guidance, and synaptogenesis. Genetic manipulation and RNA sequencing have provided insights into the molecular mechanisms underlying the effects of alternative splicing in stem cell self-renewal and neuronal fate specification. Timely expression and perhaps post-translational modification of neuron-specific splicing regulators play important roles in neuronal development. Alternative splicing of many key transcription regulators or epigenetic factors reprograms the transcriptome and hence contributes to stem cell fate determination. During neuronal differentiation, alternative splicing also modulates signaling activity, centriolar dynamics, and metabolic pathways. Moreover, alternative splicing impacts cortical lamination and neuronal development and function. In this review, we focus on recent progress toward understanding the contributions of alternative splicing to neurogenesis and brain development, which has shed light on how splicing defects may cause brain disorders and diseases.

  15. Rotation sensing with trapped ions (United States)

    Campbell, W. C.; Hamilton, P.


    We present a protocol for rotation measurement via matter-wave Sagnac interferometry using trapped ions. The ion trap based interferometer encloses a large area in a compact apparatus through repeated round-trips in a Sagnac geometry. We show how a uniform magnetic field can be used to close the interferometer over a large dynamic range in rotation speed and measurement bandwidth without contrast loss. Since this technique does not require the ions to be confined in the Lamb-Dicke regime, Doppler laser cooling should be sufficient to reach a sensitivity of { S }=1.4× {10}-6 {{rad}} {{{s}}}-1 {{{H}}{{z}}}-1/2. , which features invited work from the best early-career researchers working within the scope of J. Phys. B. This project is part of the Journal of Physics series’ 50th anniversary celebrations in 2017. Wes Campbell was selected by the Editorial Board of J. Phys. B as an Emerging Leader.

  16. SplicingTypesAnno: annotating and quantifying alternative splicing events for RNA-Seq data. (United States)

    Sun, Xiaoyong; Zuo, Fenghua; Ru, Yuanbin; Guo, Jiqiang; Yan, Xiaoyan; Sablok, Gaurav


    Alternative splicing plays a key role in the regulation of the central dogma. Four major types of alternative splicing have been classified as intron retention, exon skipping, alternative 5 splice sites or alternative donor sites, and alternative 3 splice sites or alternative acceptor sites. A few algorithms have been developed to detect splice junctions from RNA-Seq reads. However, there are few tools targeting at the major alternative splicing types at the exon/intron level. This type of analysis may reveal subtle, yet important events of alternative splicing, and thus help gain deeper understanding of the mechanism of alternative splicing. This paper describes a user-friendly R package, extracting, annotating and analyzing alternative splicing types for sequence alignment files from RNA-Seq. SplicingTypesAnno can: (1) provide annotation for major alternative splicing at exon/intron level. By comparing the annotation from GTF/GFF file, it identifies the novel alternative splicing sites; (2) offer a convenient two-level analysis: genome-scale annotation for users with high performance computing environment, and gene-scale annotation for users with personal computers; (3) generate a user-friendly web report and additional BED files for IGV visualization. SplicingTypesAnno is a user-friendly R package for extracting, annotating and analyzing alternative splicing types at exon/intron level for sequence alignment files from RNA-Seq. It is publically available at or Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Alcoholism and Alternative Splicing of Candidate Genes

    Directory of Open Access Journals (Sweden)

    Toshikazu Sasabe


    Full Text Available Gene expression studies have shown that expression patterns of several genes have changed during the development of alcoholism. Gene expression is regulated not only at the level of transcription but also through alternative splicing of pre-mRNA. In this review, we discuss some of the evidence suggesting that alternative splicing of candidate genes such as DRD2 (encoding dopamine D2 receptor may form the basis of the mechanisms underlying the pathophysiology of alcoholism. These reports suggest that aberrant expression of splice variants affects alcohol sensitivities, and alcohol consumption also regulates alternative splicing. Thus, investigations of alternative splicing are essential for understanding the molecular events underlying the development of alcoholism.

  18. Developing Successful Global Leaders (United States)

    Training, 2011


    Everyone seems to agree the world desperately needs strong leaders who can manage a global workforce and all the inherent challenges that go with it. That's a big part of the raison d'etre for global leadership development programs. But are today's organizations fully utilizing these programs to develop global leaders, and, if so, are they…

  19. Developing Global Transformational Leaders

    DEFF Research Database (Denmark)

    Ramsey, Jase R.; Rutti, Raina M.; Lorenz, Melanie P.


    Despite significant increases in training and development of global managers, little is known about the precursors of transformational leadership in Multilatinas. While prior cross-cultural literature suggests that being an autocratic leader is ideal in Multilatinas, using transformational leader...... of transformational leadership because they are better able to understand the differences of other cultures, and appropriately adjust their behavior....

  20. Leaders from Nursing's History. (United States)

    Fondiller, Shirley H.; And Others


    Looks at the lives and accomplishments of four leaders in professional nursing: (1) Loretta Ford, who championed the cause of nurse practitioners; (2) Mable Staupers, a pioneer in community health and nursing; (3) Janet Geister, a leader in private nursing; and (4) Isabel Stewart, who led the movement to standardize nursing education. (JOW)

  1. Demands for School Leaders (United States)

    Bradley-Levine, Jill


    This article examines the ways that graduate courses in teacher leadership influenced the ways that teachers described the nature of leadership and their role as educational leaders. Using Foster's (1989) four demands for school leaders as a theoretical framework, participants' perceptions are examined to determine how teachers synthesized their…

  2. Spliced

    DEFF Research Database (Denmark)

    Addison, Courtney Page


    Human gene therapy (HGT) aims to cure disease by inserting or editing the DNA of patients with genetic conditions. Since foundational genetic techniques came into use in the 1970s, the field has developed to the point that now three therapies have market approval, and over 1800 clinical trials have...... been initiated. In this article I present a brief history of HGT, showing how the ethical and practical viability of the field was achieved by key scientific and regulatory actors. These parties carefully articulated gene therapy’s scope, limiting it to therapeutic interventions on somatic cells......, and cultivated alliances and divisions that bolstered the field’s legitimacy. At times these measures faltered, and then practitioners and sometimes patients would invoke an ethical imperative, posing gene therapy as the best solution to life and death problems. I suggest that we consider how boundary...

  3. Globalisation Trapped

    Directory of Open Access Journals (Sweden)

    João Caraça


    Full Text Available The promise of making society progress through the direct applications of science was finally fulfilled in the mid-20th century. Science progressed immensely, propelled by the effects of the two world wars. The first science-based technologies saw the daylight during the 1940s and their transformative power was such that neither the military, nor subsequently the markets, allowed science to return intact to its curiosity-driven nest. Technoscience was born then and (being progressively pulled away from curiosity-driven science was able to grow enormously, erecting a formidable structure of networks of institutions that impacted decisively on the economy. It is a paradox, or maybe a trap, that the fulfillment of science’s solemn promise of ‘transforming nature’ means seeing ourselves and our Western societies entangled in crises after crises with no clear outcome in view. A redistribution of geopolitical power is under way, along with the deployment of information and communication technologies, forcing dominant structures to oscillate, as knowledge about organization and methods, marketing, design, and software begins to challenge the role of technoscience as the main vector of economic growth and wealth accumulation. What ought to be done?

  4. Depolarization-mediated regulation of alternative splicing

    Directory of Open Access Journals (Sweden)

    Alok eSharma


    Full Text Available Alternative splicing in eukaryotes plays an important role in regulating gene expression by selectively including alternative exons. A wealth of information has been accumulated that explains how alternative exons are selected in a developmental stage- or tissue-specific fashion. However, our knowledge of how cells respond to environmental changes to alter alternative splicing is very limited. For example, although a number of alternative exons have been shown to be regulated by calcium level alterations, the underlying mechanisms are not well understood. As calcium signaling in neurons plays a crucial role in essential neuronal functions such as learning and memory formation, it is important to understand how this process is regulated at every level in gene expression. The significance of the dynamic control of alternative splicing in response to changes of calcium levels has been largely unappreciated. In this communication, we will summarize the recent advances in calcium signaling-mediated alternative splicing that have provided some insights into the important regulatory mechanisms. In addition to describing the cis-acting RNA elements on the pre-mRNA molecules that respond to changes of intracellular calcium levels, we will summarize how splicing regulators change and affect alternative splicing in this process. We will also discuss a novel mode of calcium-mediated splicing regulation at the level of chromatin structure and transcription.

  5. RAGE splicing variants in mammals. (United States)

    Sterenczak, Katharina Anna; Nolte, Ingo; Murua Escobar, Hugo


    The receptor for advanced glycation end products (RAGE) is a multiligand receptor of environmental stressors which plays key roles in pathophysiological processes, including immune/inflammatory disorders, Alzheimer's disease, diabetic arteriosclerosis, tumorigenesis, and metastasis. Besides the full-length RAGE protein in humans nearly 20 natural occurring RAGE splicing variants were described on mRNA and protein level. These naturally occurring isoforms are characterized by either N-terminally or C-terminally truncations and are discussed as possible regulators of the full-length RAGE receptor either by competitive ligand binding or by displacing the full-length protein in the membrane. Accordingly, expression deregulations of the naturally occurring isoforms were supposed to have significant effect on RAGE-mediated disorders. Thereby the soluble C-truncated RAGE isoforms present in plasma and tissues are the mostly focused isoforms in research and clinics. Deregulations of the circulating levels of soluble RAGE forms were reported in several RAGE-associated pathological disorders including for example atherosclerosis, diabetes, renal failure, Alzheimer's disease, and several cancer types. Regarding other mammalian species, the canine RAGE gene showed high similarities to the corresponding human structures indicating RAGE to be evolutionary highly conserved between both species. Similar to humans the canine RAGE showed a complex and extensive splicing activity leading to a manifold pattern of RAGE isoforms. Due to the similarities seen in several canine and human diseases-including cancer-comparative structural and functional analyses allow the development of RAGE and ligand-specific therapeutic approaches beneficial for human and veterinary medicine.

  6. Cryogenic surface ion traps

    International Nuclear Information System (INIS)

    Niedermayr, M.


    Microfabricated surface traps are a promising architecture to realize a scalable quantum computer based on trapped ions. In principle, hundreds or thousands of surface traps can be located on a single substrate in order to provide large arrays of interacting ions. To this end, trap designs and fabrication methods are required that provide scalable, stable and reproducible ion traps. This work presents a novel surface-trap design developed for cryogenic applications. Intrinsic silicon is used as the substrate material of the traps. The well-developed microfabrication and structuring methods of silicon are utilized to create simple and reproducible traps. The traps were tested and characterized in a cryogenic setup. Ions could be trapped and their life time and motional heating were investigated. Long ion lifetimes of several hours were observed and the measured heating rates were reproducibly low at around 1 phonon per second at a trap frequency of 1 MHz. (author) [de

  7. Splicing pattern - ASTRA | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available List Contact us ASTRA Splicing pattern Data detail Data name Splicing pattern DOI 10.18908/lsdba.nbdc00371-0...04 Description of data contents The patterns of alternative splicing/transcriptional initiation Data file Fi...le name: File URL: Data acquisition method For the five organisms (H. sapiens, M. musculus...apping data into bit arrays, detection of splicing patterns and distribution to t

  8. Regular languages, regular grammars and automata in splicing systems (United States)

    Mohamad Jan, Nurhidaya; Fong, Wan Heng; Sarmin, Nor Haniza


    Splicing system is known as a mathematical model that initiates the connection between the study of DNA molecules and formal language theory. In splicing systems, languages called splicing languages refer to the set of double-stranded DNA molecules that may arise from an initial set of DNA molecules in the presence of restriction enzymes and ligase. In this paper, some splicing languages resulted from their respective splicing systems are shown. Since all splicing languages are regular, languages which result from the splicing systems can be further investigated using grammars and automata in the field of formal language theory. The splicing language can be written in the form of regular languages generated by grammar. Besides that, splicing systems can be accepted by automata. In this research, two restriction enzymes are used in splicing systems namely BfuCI and NcoI.

  9. Authenticating the Leader

    DEFF Research Database (Denmark)

    Johnsen, Christian Garmann

    As authentic leadership, with its dictum of being true to the self, has become increasingly influential among practitioners and mainstream leadership scholars, critical writers have drawn attention to the negative consequences of this development. Yet, few scholars have investigated the problem...... of authentication within discourse of authentic leadership. If authentic leadership is to make any sense, it is necessary to be able to distinguish the authentic from the inauthentic leader – in other words, it is necessary to authenticate the leader. This paper uses Gilles Deleuze’s reading of Plato as the point...... of departure for discussing the problem of authentication – separating the authentic leader form the inauthentic one – in the leadership guru Bill George’s model of authentic leadership. By doing so, the paper offers a way of conceptualizing the problem of authenticating leaders, as well as challenging...

  10. Leading Strategic Leader Teams

    National Research Council Canada - National Science Library

    Burleson, Willard M


    .... Although only 1 to 2 percent of the Army's senior leaders will attain a command position of strategic leadership, they are assisted by others, not only by teams specifically designed and structured...

  11. Senior Leader Credibility

    National Research Council Canada - National Science Library

    Moosmann, Christopher


    .... Leadership at senior levels involves a different type of work than at lower organizational levels and this requires leaders to possess a different set of skills, knowledge, and attributes in order to be successful...

  12. Persuasion: A Leader's Edge

    National Research Council Canada - National Science Library

    McGuire, Mark


    .... Persuasive argument is a vital aspect of strategic leadership. Any leader faced with the inherent complexities of leading his or her organization through transformational change must be capable of persuading...

  13. Narcissism and Toxic Leaders (United States)


    Examples of unconscious behaviors could include brushing one’s teeth , getting dressed, or even driving a car—an individual can day-dream about a meeting...enhance its positive attributes and raise awareness of its negative ones. By definition, narcissistic leaders have “an inflated sense of self- importance ...for leaders, especially in the military, there are aspects of narcissism that are appropriate (if controlled and self-regulated) and important for

  14. Leader self-definition and leader self-serving behavior

    NARCIS (Netherlands)

    Rus, Diana; van Knippenberg, Daan; Wisse, Barbara

    The present research investigated the relationship between leader self-definition processes and leader self-serving behaviors. We hypothesized that self-definition as a leader interacts with social reference information (descriptive and injunctive) in predicting leader self-serving actions Six

  15. Protein splicing and its evolution in eukaryotes

    Directory of Open Access Journals (Sweden)

    Starokadomskyy P. L.


    Full Text Available Inteins, or protein introns, are parts of protein sequences that are post-translationally excised, their flanking regions (exteins being spliced together. This process was called protein splicing. Originally inteins were found in prokaryotic or unicellular eukaryotic organisms. But the general principles of post-translation protein rearrangement are evolving yielding different post-translation modification of proteins in multicellular organisms. For clarity, these non-intein mediated events call either protein rearrangements or protein editing. The most intriguing example of protein editing is proteasome-mediated splicing of antigens in vertebrates that may play important role in antigen presentation. Other examples of protein rearrangements are maturation of Hg-proteins (critical receptors in embryogenesis as well as maturation of several metabolic enzymes. Despite a lack of experimental data we try to analyze some intriguing examples of protein splicing evolution.

  16. HOLLYWOOD: a comparative relational database of alternative splicing. (United States)

    Holste, Dirk; Huo, George; Tung, Vivian; Burge, Christopher B


    RNA splicing is an essential step in gene expression, and is often variable, giving rise to multiple alternatively spliced mRNA and protein isoforms from a single gene locus. The design of effective databases to support experimental and computational investigations of alternative splicing (AS) is a significant challenge. In an effort to integrate accurate exon and splice site annotation with current knowledge about splicing regulatory elements and predicted AS events, and to link information about the splicing of orthologous genes in different species, we have developed the Hollywood system. This database was built upon genomic annotation of splicing patterns of known genes derived from spliced alignment of complementary DNAs (cDNAs) and expressed sequence tags, and links features such as splice site sequence and strength, exonic splicing enhancers and silencers, conserved and non-conserved patterns of splicing, and cDNA library information for inferred alternative exons. Hollywood was implemented as a relational database and currently contains comprehensive information for human and mouse. It is accompanied by a web query tool that allows searches for sets of exons with specific splicing characteristics or splicing regulatory element composition, or gives a graphical or sequence-level summary of splicing patterns for a specific gene. A streamlined graphical representation of gene splicing patterns is provided, and these patterns can alternatively be layered onto existing information in the UCSC Genome Browser. The database is accessible at

  17. Mechanism of alternative splicing and its regulation. (United States)

    Wang, Yan; Liu, Jing; Huang, B O; Xu, Yan-Mei; Li, Jing; Huang, Lin-Feng; Lin, Jin; Zhang, Jing; Min, Qing-Hua; Yang, Wei-Ming; Wang, Xiao-Zhong


    Alternative splicing of precursor mRNA is an essential mechanism to increase the complexity of gene expression, and it plays an important role in cellular differentiation and organism development. Regulation of alternative splicing is a complicated process in which numerous interacting components are at work, including cis-acting elements and trans-acting factors, and is further guided by the functional coupling between transcription and splicing. Additional molecular features, such as chromatin structure, RNA structure and alternative transcription initiation or alternative transcription termination, collaborate with these basic components to generate the protein diversity due to alternative splicing. All these factors contributing to this one fundamental biological process add up to a mechanism that is critical to the proper functioning of cells. Any corruption of the process may lead to disruption of normal cellular function and the eventuality of disease. Cancer is one of those diseases, where alternative splicing may be the basis for the identification of novel diagnostic and prognostic biomarkers, as well as new strategies for therapy. Thus, an in-depth understanding of alternative splicing regulation has the potential not only to elucidate fundamental biological principles, but to provide solutions for various diseases.

  18. Thermopriming Triggers Splicing Memory in Arabidopsis

    KAUST Repository

    Ling, Yu


    Abiotic and biotic stresses limit crop productivity. Exposure to a non-lethal stress, referred to as priming, can allow plants to survive subsequent and otherwise lethal conditions; the priming effect persists even after a prolonged stress-free period. However, the molecular mechanisms underlying priming are not fully understood. Here, we investigated the molecular basis of heat shock memory and the role of priming in Arabidopsisthaliana. Comprehensive analysis of transcriptome-wide changes in gene expression and alternative splicing in primed and non-primed plants revealed that alternative splicing functions as a novel component of heat shock memory. We show that priming of plants with a non-lethal heat stress results in de-repression of splicing after a second exposure to heat stress. By contrast, non-primed plants showed significant repression of splicing. These observations link ‘splicing memory’ to the ability of plants to survive subsequent and otherwise lethal heat stress. This newly discovered priming-induced splicing memory may represent a general feature of heat stress responses in plants and other organisms as many of the key components of heat shock responses are conserved among eukaryotes. Furthermore, this finding could facilitate the development of novel approaches to improve plant survival under extreme heat stress.

  19. Four mistakes leaders keep making. (United States)

    Schaffer, Robert H


    Again and again, senior managers fall into four behavioral traps that thwart organizational change. The behaviors are difficult to recognize and reverse because they serve to protect egos and prevent anxiety--but executives can overcome them. First, managers fail to set proper expectations. When they announce major directional changes or new goals, they don't spell out credible plans or specify who's accountable. Second, they excuse subordinates from the pursuit of overall goals, allowing people to remain preoccupied with their own units. Third, executives essentially collude with staff experts and consultants by going along with a deeply flawed contract: The experts agree to deliver and implement a "product" (a new system, for instance) but don't include measurable gains as part of the deal. Fourth, managers wait while associates overprepare. After challenging their employees to make needed improvements, they accept the response "Yes, but first we have to..." Finish the sentence: Train our people. Set up focus groups. Bring in Six Sigma. And so on. The best way to confront the traps is to conduct small personal experiments that rapidly produce tangible results, incur little risk of failure, and are confined enough to demonstrate a clear link between trial and outcome. For example, one iron plant addressed quality problems by targeting five areas for improvement, setting clear and measurable goals for each, and holding team Leaders accountable for outcomes. AlL five experiments succeeded and were extended to the rest of the plant. Quality problems eased up within 100 days and virtually disappeared a few months later.

  20. Leaders produce leaders and managers produce followers (United States)

    Khoshhal, Khalid I.; Guraya, Salman Y.


    Objectives: To elaborate the desired qualities, traits, and styles of physician’s leadership with a deep insight into the recommended measures to inculcate leadership skills in physicians. Methods: The databases of MEDLINE, EMBASE, CINAHL, and the Cochrane Library were searched for the full-text English-language articles published during the period 2000-2015. Further search, including manual search of grey literature, was conducted from the bibliographic list of all included articles. Medical Subject Headings (MeSH) keywords “Leadership” AND “Leadership traits” AND “Leadership styles” AND “Physicians’ leadership” AND “Tomorrow’s doctors” were used for the literature search. This search followed a step-wise approach defined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The retrieved bibliographic list was analyzed and non-relevant material such as abstracts, conference proceedings, letters to editor, and short communications were excluded. Finally, 21 articles were selected for this review. Results: The literature search showed a number of leadership courses and formal training programs that can transform doctors to physician leaders. Leaders can inculcate confidence by integrating diverse views and listening; supporting skillful conversations through dialogue and helping others assess their influence and expertise. In addition to their clinical competence, physician leaders need to acquire the industry knowledge (clinical processes, health-care trends, budget), problem-solving skills, and emotional intelligence. Conclusion: This review emphasizes the need for embedding formal leadership courses in the medical curricula for fostering tomorrow doctors’ leadership and organizational skills. The in-house and off-campus training programs and workshops should be arranged for grooming the potential candidates for effective leadership. PMID:27652355

  1. Clinical, in silico, and experimental evidence for pathogenicity of two novel splice site mutations in the SH3TC2 gene

    Czech Academy of Sciences Publication Activity Database

    Laššuthová, P.; Gregor, Martin; Sarnová, Lenka; Machalová, Eliška; Sedláček, Radislav; Seeman, P.


    Roč. 26, 3-4 (2012), s. 413-420 ISSN 0167-7063 R&D Projects: GA ČR GAP303/10/2044 Institutional support: RVO:68378050 Keywords : exon trapping * peripheral neuropathy * SH3TC2 gene * splice site mutation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.159, year: 2012

  2. BRCA1 Exon 11, a CERES (Composite Regulatory Element of Splicing Element Involved in Splice Regulation

    Directory of Open Access Journals (Sweden)

    Claudia Tammaro


    Full Text Available Unclassified variants (UV of BRCA1 can affect normal pre-mRNA splicing. Here, we investigate the UV c.693G>A, a “silent” change in BRCA1 exon 11, which we have found induces aberrant splicing in patient carriers and in vitro. Using a minigene assay, we show that the UV c.693G>A has a strong effect on the splicing isoform ratio of BRCA1. Systematic site-directed mutagenesis of the area surrounding the nucleotide position c.693G>A induced variable changes in the level of exon 11 inclusion/exclusion in the mRNA, pointing to the presence of a complex regulatory element with overlapping enhancer and silencer functions. Accordingly, protein binding analysis in the region detected several splicing regulatory factors involved, including SRSF1, SRSF6 and SRSF9, suggesting that this sequence represents a composite regulatory element of splicing (CERES.

  3. Vitamin D and alternative splicing of RNA. (United States)

    Zhou, Rui; Chun, Rene F; Lisse, Thomas S; Garcia, Alejandro J; Xu, Jianzhong; Adams, John S; Hewison, Martin


    The active form of vitamin D (1α,25-dihydroxyvitamin D, 1,25(OH)2D) exerts its genomic effects via binding to a nuclear high-affinity vitamin D receptor (VDR). Recent deep sequencing analysis of VDR binding locations across the complete genome has significantly expanded our understanding of the actions of vitamin D and VDR on gene transcription. However, these studies have also promoted appreciation of the extra-transcriptional impact of vitamin D on gene expression. It is now clear that vitamin D interacts with the epigenome via effects on DNA methylation, histone acetylation, and microRNA generation to maintain normal biological functions. There is also increasing evidence that vitamin D can influence pre-mRNA constitutive splicing and alternative splicing, although the mechanism for this remains unclear. Pre-mRNA splicing has long been thought to be a post-transcription RNA processing event, but current data indicate that this occurs co-transcriptionally. Several steroid hormones have been recognized to coordinately control gene transcription and pre-mRNA splicing through the recruitment of nuclear receptor co-regulators that can both control gene transcription and splicing. The current review will discuss this concept with specific reference to vitamin D, and the potential role of heterogeneous nuclear ribonucleoprotein C (hnRNPC), a nuclear factor with an established function in RNA splicing. hnRNPC, has been shown to be involved in the VDR transcriptional complex as a vitamin D-response element-binding protein (VDRE-BP), and may act as a coupling factor linking VDR-directed gene transcription with RNA splicing. In this way hnRNPC may provide an additional mechanism for the fine-tuning of vitamin D-regulated target gene expression. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Modulation of 5' splice site selection using tailed oligonucleotides carrying splicing signals

    Directory of Open Access Journals (Sweden)

    Elela Sherif


    Full Text Available Abstract Background We previously described the use of tailed oligonucleotides as a means of reprogramming alternative pre-mRNA splicing in vitro and in vivo. The tailed oligonucleotides that were used interfere with splicing because they contain a portion complementary to sequences immediately upstream of the target 5' splice site combined with a non-hybridizing 5' tail carrying binding sites for the hnRNP A1/A2 proteins. In the present study, we have tested the inhibitory activity of RNA oligonucleotides carrying different tail structures. Results We show that an oligonucleotide with a 5' tail containing the human β-globin branch site sequence inhibits the use of the 5' splice site of Bcl-xL, albeit less efficiently than a tail containing binding sites for the hnRNP A1/A2 proteins. A branch site-containing tail positioned at the 3' end of the oligonucleotide also elicited splicing inhibition but not as efficiently as a 5' tail. The interfering activity of a 3' tail was improved by adding a 5' splice site sequence next to the branch site sequence. A 3' tail carrying a Y-shaped branch structure promoted similar splicing interference. The inclusion of branch site or 5' splice site sequences in the Y-shaped 3' tail further improved splicing inhibition. Conclusion Our in vitro results indicate that a variety of tail architectures can be used to elicit splicing interference at low nanomolar concentrations, thereby broadening the scope and the potential impact of this antisense technology.

  5. Homologous SV40 RNA trans-splicing: Special case or prime example of viral RNA trans-splicing?

    Directory of Open Access Journals (Sweden)

    Sushmita Poddar


    Full Text Available To date the Simian Virus 40 (SV40 is the only proven example of a virus that recruits the mechanism of RNA trans-splicing to diversify its sequences and gene products. Thereby, two identical viral transcripts are efficiently joined by homologous trans-splicing triggering the formation of a highly transforming 100 kDa super T antigen. Sequences of other viruses including HIV-1 and the human adenovirus type 5 were reported to be involved in heterologous trans-splicing towards cellular or viral sequences but the meaning of these events remains unclear. We computationally and experimentally investigated molecular features associated with viral RNA trans-splicing and identified a common pattern: Viral RNA trans-splicing occurs between strong cryptic or regular viral splice sites and strong regular or cryptic splice sites of the trans-splice partner sequences. The majority of these splice sites are supported by exonic splice enhancers. Splice sites that could compete with the trans-splicing sites for cis-splice reactions are weaker or inexistent. Finally, all but one of the trans-splice reactions seem to be facilitated by one or more complementary binding domains of 11 to 16 nucleotides in length which, however occur with a statistical probability close to one for the given length of the involved sequences. The chimeric RNAs generated via heterologous viral RNA trans-splicing either did not lead to fusion proteins or led to proteins of unknown function. Our data suggest that distinct viral RNAs are highly susceptible to trans-splicing and that heterologous viral trans-splicing, unlike homologous SV40 trans-splicing, represents a chance event.

  6. Principals as Instructional Leaders (United States)

    Finkel, Ed


    At some level, principals always have been instructional leaders--but never before has their role been more prominent. First, the accountability movement--No Child Left Behind (NCLB) in particular--thrust principals into the spotlight on academic achievement. Then budget cuts peeled away capacity at both the district and school levels, thinning…

  7. Authenticating the Leader

    DEFF Research Database (Denmark)

    Garmann Johnsen, Christian


    In the wake of a series of corporate scandals, there has been a growing call for authentic leadership in order to ensure ethical conduct in contemporary organizations. Authentic leadership, however, depends upon the ability to draw a distinction between the authentic and inauthentic leader. This ...... or her own value-commitments....

  8. Widespread evolutionary conservation of alternatively spliced exons in caenorhabditis

    DEFF Research Database (Denmark)

    Irimia, Manuel; Rukov, Jakob L; Penny, David


    Alternative splicing (AS) contributes to increased transcriptome and proteome diversity in various eukaryotic lineages. Previous studies showed low levels of conservation of alternatively spliced (cassette) exons within mammals and within dipterans. We report a strikingly different pattern in Cae...

  9. Strategic Military Leaders - Leading Tomorrow

    National Research Council Canada - National Science Library

    Kit, Ng W


    .... Four key leadership competencies stand out. We need strategic leaders who are good at doing the right things and doing things right leaders who have the mental agility to choose the correct goals to achieve, the social intelligence to inspire...

  10. Identification of Common Genetic Variation That Modulates Alternative Splicing


    Hull, Jeremy; Campino, Susana; Rowlands, Kate; Chan, Man-Suen; Copley, Richard R; Taylor, Martin S; Rockett, Kirk; Elvidge, Gareth; Keating, Brendan; Knight, Julian; Kwiatkowski, Dominic


    Alternative splicing of genes is an efficient means of generating variation in protein function. Several disease states have been associated with rare genetic variants that affect splicing patterns. Conversely, splicing efficiency of some genes is known to vary between individuals without apparent ill effects. What is not clear is whether commonly observed phenotypic variation in splicing patterns, and hence potential variation in protein function, is to a significant extent determined by nat...

  11. Universal Alternative Splicing of Noncoding Exons

    DEFF Research Database (Denmark)

    Deveson, Ira W; Brunck, Marion E; Blackburn, James


    The human transcriptome is so large, diverse, and dynamic that, even after a decade of investigation by RNA sequencing (RNA-seq), we have yet to resolve its true dimensions. RNA-seq suffers from an expression-dependent bias that impedes characterization of low-abundance transcripts. We performed......, indicative of regulation by a deeply conserved splicing code. We propose that noncoding exons are functionally modular, with alternative splicing generating an enormous repertoire of potential regulatory RNAs and a rich transcriptional reservoir for gene evolution....

  12. SPA: a probabilistic algorithm for spliced alignment.

    Directory of Open Access Journals (Sweden)


    Full Text Available Recent large-scale cDNA sequencing efforts show that elaborate patterns of splice variation are responsible for much of the proteome diversity in higher eukaryotes. To obtain an accurate account of the repertoire of splice variants, and to gain insight into the mechanisms of alternative splicing, it is essential that cDNAs are very accurately mapped to their respective genomes. Currently available algorithms for cDNA-to-genome alignment do not reach the necessary level of accuracy because they use ad hoc scoring models that cannot correctly trade off the likelihoods of various sequencing errors against the probabilities of different gene structures. Here we develop a Bayesian probabilistic approach to cDNA-to-genome alignment. Gene structures are assigned prior probabilities based on the lengths of their introns and exons, and based on the sequences at their splice boundaries. A likelihood model for sequencing errors takes into account the rates at which misincorporation, as well as insertions and deletions of different lengths, occurs during sequencing. The parameters of both the prior and likelihood model can be automatically estimated from a set of cDNAs, thus enabling our method to adapt itself to different organisms and experimental procedures. We implemented our method in a fast cDNA-to-genome alignment program, SPA, and applied it to the FANTOM3 dataset of over 100,000 full-length mouse cDNAs and a dataset of over 20,000 full-length human cDNAs. Comparison with the results of four other mapping programs shows that SPA produces alignments of significantly higher quality. In particular, the quality of the SPA alignments near splice boundaries and SPA's mapping of the 5' and 3' ends of the cDNAs are highly improved, allowing for more accurate identification of transcript starts and ends, and accurate identification of subtle splice variations. Finally, our splice boundary analysis on the human dataset suggests the existence of a novel non

  13. Shrew trap efficiency

    DEFF Research Database (Denmark)

    Gambalemoke, Mbalitini; Mukinzi, Itoka; Amundala, Drazo


    We investigated the efficiency of four trap types (pitfall, Sherman LFA, Victor snap and Museum Special snap traps) to capture shrews. This experiment was conducted in five inter-riverine forest blocks in the region of Kisangani. The total trapping effort was 6,300, 9,240, 5,280 and 5,460 trap......-nights for the pitfall, Sherman, Victor and Museum Special traps, respectively. In total, we captured 366 shrews. The use of pitfall traps yielded the highest trapping success (4.1) with at least 18 shrew species identified. Trapping success and the number of species collected was lower for the Sherman (0.6, at least 11...... species), Victor (0.6, at least 8 species) and Museum Special (0.5, at least 6 species) traps. Although Crocidura olivieri and C. denti were caught using all four trap types, captures with different trap types did not produce a sample with the same taxonomic composition. In agreement with previous studies...

  14. Christian School Leaders and Spirituality (United States)

    Banke, Susan; Maldonado, Nancy; Lacey, Candace H.


    This phenomenological study examined the spiritual experiences of Christian school leaders who are the spiritual leaders of their schools. A purposeful, nominated sample of 12 Christian school leaders was selected. In-depth, open-ended interviews were conducted, audio taped, and then transcribed verbatim. Data analysis was based on Rudestam and…

  15. Are radiography lecturers, leaders?

    International Nuclear Information System (INIS)

    Hendry, Julie Anne


    This review article aims to explore the concept of radiography lecturers acting as leaders to their student followers. Through a brief review of the literature, a definition of leadership is suggested and some leadership theories explored. The path-goal theory, leader–member exchange theory and the contemporary theory of transformational leadership are examined more closely. Links between lecturer-leader behaviour and student motivation and learning are tentatively suggested with transformational leadership appearing to offer the optimal leadership style for lecturers to adopt. The paucity of literature relating directly to radiography is acknowledged and areas for further research are suggested. The article concludes with some of the author's practical ideas for incorporating transformational leadership styles and behaviours into radiography education today

  16. What makes a leader? (United States)

    Goleman, D


    Superb leaders have very different ways of directing a team, a division, or a company. Some are subdued and analytical; others are charismatic and go with their gut. And different situations call for different types of leadership. Most mergers need a sensitive negotiator at the helm, whereas many turnarounds require a more forceful kind of authority. Psychologist and noted author Daniel Goleman has found, however, that effective leaders are alike in one crucial way: they all have a high degree of what has come to be known as emotional intelligence. In fact, Goleman's research at nearly 200 large, global companies revealed that emotional intelligence--especially at the highest levels of a company--is the sine qua non for leadership. Without it, a person can have first-class training, an incisive mind, and an endless supply of good ideas, but he still won't make a great leader. The components of emotional intelligence--self-awareness, self-regulation, motivation, empathy, and social skill--can sound unbusinesslike. But exhibiting emotional intelligence at the workplace does not mean simply controlling your anger or getting along with people. Rather, it means understanding your own and other people's emotional makeup well enough to move people in the direction of accomplishing your company's goals. In this article, the author discusses each component of emotional intelligence and shows through examples how to recognize it in potential leaders, how and why it leads to measurable business results, and how it can be learned. It takes time and, most of all, commitment. But the benefits that come from having a well-developed emotional intelligence, both for the individual and the organization, make it worth the effort.

  17. The wise leader. (United States)

    Nonaka, Ikujiro; Takeuchi, Hirotaka


    In an era of increasing discontinuity, wise leadership has nearly vanished. Many leaders find it difficult to reinvent their corporations rapidly enough to cope with new technologies, demographic shifts, and consumption trends. They can't develop truly global organizations that operate effortlessly across borders. And they find it tough to ensure that their people adhere to values and ethics. The authors assert that leaders must acquire practical wisdom, or what Aristotle called phronesis: experiential knowledge that enables people to make ethically sound judgments. Wise leaders demonstrate six abilities: (i) They make decisions on the basis of what is good for the organization and for society. (2) They quickly grasp the essence of a situation and fathom the nature and meaning of people, things, and events. (3) They provide contexts in which executives and employees can interact to create new meaning. (4) They employ metaphors and stories to convert their experience into tacit knowledge that others can use. (5) They exert political power to bring people together and spur them to act. (6) They use apprenticeship and mentoring to cultivate practical wisdom in orders.

  18. The hnRNP 2H9 gene, which is involved in the splicing reaction, is a multiply spliced gene

    DEFF Research Database (Denmark)

    Honoré, B


    The hnRNP 2H9 gene products are involved in the splicing process and participate in early heat shock-induced splicing arrest. By combining low/high stringency hybridisation, database search, Northern and Western blotting it is shown that the gene is alternatively spliced into at least six transcr...

  19. Auxiliary splice factor U2AF26 and transcription factor Gfi1 cooperate directly in regulating CD45 alternative splicing.

    NARCIS (Netherlands)

    Heyd, F.; Dam, G.B. ten; Moroy, T.


    By alternative splicing, different isoforms of the transmembrane tyrosine phosphatase CD45 are generated that either enhance or limit T cell receptor signaling. We report here that CD45 alternative splicing is regulated by cooperative action of the splice factor U2AF26 and the transcription factor

  20. A contracted DNA repeat in LHX3 intron 5 is associated with aberrant splicing and pituitary dwarfism in German shepherd dogs.

    Directory of Open Access Journals (Sweden)

    Annemarie M W Y Voorbij

    Full Text Available Dwarfism in German shepherd dogs is due to combined pituitary hormone deficiency of unknown genetic cause. We localized the recessively inherited defect by a genome wide approach to a region on chromosome 9 with a lod score of 9.8. The region contains LHX3, which codes for a transcription factor essential for pituitary development. Dwarfs have a deletion of one of six 7 bp repeats in intron 5 of LHX3, reducing the intron size to 68 bp. One dwarf was compound heterozygous for the deletion and an insertion of an asparagine residue in the DNA-binding homeodomain of LHX3, suggesting involvement of the gene in the disorder. An exon trapping assay indicated that the shortened intron is not spliced efficiently, probably because it is too small. We applied bisulfite conversion of cytosine to uracil in RNA followed by RT-PCR to analyze the splicing products. The aberrantly spliced RNA molecules resulted from either skipping of exon 5 or retention of intron 5. The same splicing defects were observed in cDNA derived from the pituitary of dwarfs. A survey of similarly mutated introns suggests that there is a minimal distance requirement between the splice donor and branch site of 50 nucleotides. In conclusion, a contraction of a DNA repeat in intron 5 of canine LHX3 leads to deficient splicing and is associated with pituitary dwarfism.

  1. Capillary Electrophoresis Analysis of Conventional Splicing Assays

    DEFF Research Database (Denmark)

    de Garibay, Gorka Ruiz; Acedo, Alberto; García-Casado, Zaida


    of these assays is often challenging. Here, we explore this issue by conducting splicing assays in 31 BRCA2 genetic variants. All variants were assessed by RT-PCR followed by capillary electrophoresis and direct sequencing. If assays did not produce clear-cut outputs (Class-2 or Class-5 according to analytical...

  2. Survey of gene splicing algorithms based on reads. (United States)

    Si, Xiuhua; Wang, Qian; Zhang, Lei; Wu, Ruo; Ma, Jiquan


    Gene splicing is the process of assembling a large number of unordered short sequence fragments to the original genome sequence as accurately as possible. Several popular splicing algorithms based on reads are reviewed in this article, including reference genome algorithms and de novo splicing algorithms (Greedy-extension, Overlap-Layout-Consensus graph, De Bruijn graph). We also discuss a new splicing method based on the MapReduce strategy and Hadoop. By comparing these algorithms, some conclusions are drawn and some suggestions on gene splicing research are made.

  3. Approaches to link RNA secondary structures with splicing regulation

    DEFF Research Database (Denmark)

    Plass, Mireya; Eyras, Eduardo


    by facilitating or hindering the interaction with factors and small nuclear ribonucleoproteins (snRNPs) that regulate splicing. Moreover, the secondary structure could play a fundamental role in the splicing of yeast species, which lack many of the regulatory splicing factors present in metazoans. This chapter......In higher eukaryotes, alternative splicing is usually regulated by protein factors, which bind to the pre-mRNA and affect the recognition of splicing signals. There is recent evidence that the secondary structure of the pre-mRNA may also play an important role in this process, either...

  4. Trap style influences wild pig behavior and trapping success (United States)

    Williams, B.L.; Holtfreter, R.W.; Ditchkoff, S.S.; Grand, J.B.


    Despite the efforts of many natural resource professionals, wild pig (Sus scrofa) populations are expanding in many areas of the world. Although many creative techniques for controlling pig populations are being explored, trapping has been and still is themost commonly usedmethod of population control formany public and private land managers. We conducted an observational study to examine the efficiency of 2 frequently used trap styles: a small, portable box-style trap and a larger, semi-permanent, corral-style trap.We used game cameras to examine patterns of trap entry by wild pigs around each style of trap, and we conducted a trapping session to compare trapping success between trap styles. Adult female and juvenile wild pigs entered both styles of trap more readily than did adult males, and adult males seemed particularly averse to entering box traps. Less than 10% of adult male visits to box traps resulted in entries, easily the least percentage of any class at any style of trap. Adult females entered corral traps approximately 2.2 times more often per visit than box traps and re-entered corral traps >2 times more frequently. Juveniles entered and reentered both box and corral traps at similar rates. Overall (all-class) entry-per-visit rates at corral traps (0.71) were nearly double that of box traps (0.37). Subsequent trapping data supported these preliminary entry data; the capture rate for corral traps was >4 times that of box traps. Our data suggest that corral traps are temporally and economically superior to box traps with respect to efficiency; that is, corral traps effectively trap more pigs per trap night at a lower cost per pig than do box traps. ?? 2011 The Wildlife Society.

  5. Neutral atom traps.

    Energy Technology Data Exchange (ETDEWEB)

    Pack, Michael Vern


    This report describes progress in designing a neutral atom trap capable of trapping sub millikelvin atom in a magnetic trap and shuttling the atoms across the atom chip from a collection area to an optical cavity. The numerical simulation and atom chip design are discussed. Also, discussed are preliminary calculations of quantum noise sources in Kerr nonlinear optics measurements based on electromagnetically induced transparency. These types of measurements may be important for quantum nondemolition measurements at the few photon limit.

  6. Nucleus-encoded mRNAs for chloroplast proteins GapA, PetA, and PsbO are trans-spliced in the flagellate Euglena gracilis irrespective of light and plastid function. (United States)

    Mateášiková-Kováčová, Bianka; Vesteg, Matej; Drahovská, Hana; Záhonová, Kristína; Vacula, Rostislav; Krajčovič, Juraj


    Euglena gracilis is a fresh-water flagellate possessing secondary chloroplasts of green algal origin. In contrast with organisms possessing primary plastids, mRNA levels of nucleus-encoded genes for chloroplast proteins in E. gracilis depend on neither light nor plastid function. However, it remains unknown, if all these mRNAs are trans-spliced and possess spliced leader sequence at the 5'-end and if trans-splicing depends on light or functional plastids. This study revealed that polyadenylated mRNAs encoding the chloroplast proteins glyceraldehyde-3-phosphate dehydrogenase (GapA), cytochrome f (PetA), and subunit O of photosystem II (PsbO) are trans-spliced irrespective of light or plastid function. © 2012 The Author(s) Journal of Eukaryotic Microbiology © 2012 International Society of Protistologists.

  7. Functional and evolutionary analysis of alternatively spliced genes is consistent with an early eukaryotic origin of alternative splicing

    DEFF Research Database (Denmark)

    Irimia, Manuel; Rukov, Jakob Lewin; Penny, David


    , and may therefore predate multicellularity, is still unknown. To better understand the origin and evolution of alternative splicing and its usage in diverse organisms, we studied alternative splicing in 12 eukaryotic species, comparing rates of alternative splicing across genes of different functional...... classes, cellular locations, intron/exon structures and evolutionary origins. RESULTS: For each species, we find that genes from most functional categories are alternatively spliced. Ancient genes (shared between animals, fungi and plants) show high levels of alternative splicing. Genes with products...

  8. Career anchors of dentist leaders. (United States)

    Tuononen, Tiina; Lammintakanen, Johanna; Suominen, Anna Liisa


    The work of a health care leader is demanding; in order to cope, leaders need motivation and support. The occurrence of intrinsic factors called career anchors (combination of one's competence, motives and values) could be a contributing factor in dentist leaders' career decisions. The aim of our study was to identify dentist leaders' career anchors and their association to dentist leaders' retention or turnover of the leadership position. Materials were gathered in 2014 via an electronic questionnaire from 156 current (Leaders) or former (Leavers) Finnish dentist leaders. Career anchor evaluation was conducted by the questionnaire and scoring-table taken from Edgar Schein's Career Anchors Self-Assessment. Both the most and the least important career anchors were detected by the highest and lowest scores and their occurrence reported as percentages. Associations between career anchor scores and tendency to stay were analyzed with logistic regression. 'Technical/Functional Competence' and 'Lifestyle' were most frequently reported as the most important and 'Entrepreneurial Creativity' and 'General Managerial Competence' as the least important career anchors. However, a higher level of 'General Managerial Competence' anchor was most significantly associated with staying in a leadership position. Instead, 'Pure Challenge' and 'Lifestyle' decreased the odds to stay. The knowledge of the important and essential career anchors of dentist leaders' and individuals' could perform crucial part in career choices and also in planning education, work opportunities and human resource policies promoting retention of dentist leaders and probably also other health care leaders.

  9. Development of a novel splice array platform and its application in the identification of alternative splice variants in lung cancer

    Directory of Open Access Journals (Sweden)

    Gomez-Roman Javier


    Full Text Available Abstract Background Microarrays strategies, which allow for the characterization of thousands of alternative splice forms in a single test, can be applied to identify differential alternative splicing events. In this study, a novel splice array approach was developed, including the design of a high-density oligonucleotide array, a labeling procedure, and an algorithm to identify splice events. Results The array consisted of exon probes and thermodynamically balanced junction probes. Suboptimal probes were tagged and considered in the final analysis. An unbiased labeling protocol was developed using random primers. The algorithm used to distinguish changes in expression from changes in splicing was calibrated using internal non-spliced control sequences. The performance of this splice array was validated with artificial constructs for CDC6, VEGF, and PCBP4 isoforms. The platform was then applied to the analysis of differential splice forms in lung cancer samples compared to matched normal lung tissue. Overexpression of splice isoforms was identified for genes encoding CEACAM1, FHL-1, MLPH, and SUSD2. None of these splicing isoforms had been previously associated with lung cancer. Conclusions This methodology enables the detection of alternative splicing events in complex biological samples, providing a powerful tool to identify novel diagnostic and prognostic biomarkers for cancer and other pathologies.

  10. Building leaders paving the path for emerging leaders

    CERN Document Server

    Stoner, Charles R


    Although the selection and development of emerging leaders is fundamental to organizational growth and success, many organizations are facing a troubling scenario - a striking gap between the leaders they need and the talent available to assume the mantle of leadership. This book, grounded in empirical investigations and philosophical insights into the study of leadership, is designed to help emerging leaders bridge the gap between 'new leader' and confident, respected difference maker. From the development of leadership skills to the practice and application of successful strategies, award-wi

  11. The new clinical leader. (United States)

    Oates, Kim


    The complexity and cost of health care, along with a greater need for accountability calls for a new style of clinical leadership. The new clinical leader will lead reform by putting the needs of the patient first and foremost, looking at current and planned services from the patient's point of view as well as the clinician's. Excellent clinical skills will remain essential but will be supplemented by a focus on team work and mentoring, patient safety, clear communication and reduction in waste and inefficiency, leading to better financial outcomes. The new clinical leaders will understand the importance of consulting widely and engaging colleagues in creating change to improve patient care. They will develop trusting and mutually respectful relationships with health service management and be able to negotiate the delicate balance between clinical judgement, resource constraints and personal loyalties by keeping the best outcome for the patient at the forefront of their thinking. © 2012 The Author. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  12. Torque and optical traps

    African Journals Online (AJOL)



    Dec 29, 2008 ... Optical traps are an important tool for research in the field of single molecule biophysics. Recent advances in optical trapping have extended their functionality from simple linear manipulation and measurement of forces, to now the ability to rotate objects and measure torques. This mini review summarizes ...

  13. Versatile electrostatic trap

    NARCIS (Netherlands)

    van Veldhoven, J.; Bethlem, H.L.; Schnell, M.; Meijer, G.


    A four electrode electrostatic trap geometry is demonstrated that can be used to combine a dipole, quadrupole, and hexapole field. A cold packet of ND315 molecules is confined in both a purely quadrupolar and hexapolar trapping field and additionally, a dipole field is added to a hexapole field to

  14. Quadrupole Ion Traps

    Indian Academy of Sciences (India)

    electron bound to the gravitational field, the 'geonium atom'. The first atomic hyperfine structure experiment on trapped ions was performed by Dehmelt's group using the stored-ion exchange-collision technique in a Paul trap which paved the way for some of the subsequent experiment for atomic frequency. A single atom at.

  15. Genomic HEXploring allows landscaping of novel potential splicing regulatory elements. (United States)

    Erkelenz, Steffen; Theiss, Stephan; Otte, Marianne; Widera, Marek; Peter, Jan Otto; Schaal, Heiner


    Effective splice site selection is critically controlled by flanking splicing regulatory elements (SREs) that can enhance or repress splice site use. Although several computational algorithms currently identify a multitude of potential SRE motifs, their predictive power with respect to mutation effects is limited. Following a RESCUE-type approach, we defined a hexamer-based 'HEXplorer score' as average Z-score of all six hexamers overlapping with a given nucleotide in an arbitrary genomic sequence. Plotted along genomic regions, HEXplorer score profiles varied slowly in the vicinity of splice sites. They reflected the respective splice enhancing and silencing properties of splice site neighborhoods beyond the identification of single dedicated SRE motifs. In particular, HEXplorer score differences between mutant and reference sequences faithfully represented exonic mutation effects on splice site usage. Using the HIV-1 pre-mRNA as a model system highly dependent on SREs, we found an excellent correlation in 29 mutations between splicing activity and HEXplorer score. We successfully predicted and confirmed five novel SREs and optimized mutations inactivating a known silencer. The HEXplorer score allowed landscaping of splicing regulatory regions, provided a quantitative measure of mutation effects on splice enhancing and silencing properties and permitted calculation of the mutationally most effective nucleotide. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Evolution of Nova-dependent splicing regulation in the brain.

    Directory of Open Access Journals (Sweden)

    Nejc Jelen


    Full Text Available A large number of alternative exons are spliced with tissue-specific patterns, but little is known about how such patterns have evolved. Here, we study the conservation of the neuron-specific splicing factors Nova1 and Nova2 and of the alternatively spliced exons they regulate in mouse brain. Whereas Nova RNA binding domains are 94% identical across vertebrate species, Nova-dependent splicing silencer and enhancer elements (YCAY clusters show much greater divergence, as less than 50% of mouse YCAY clusters are conserved at orthologous positions in the zebrafish genome. To study the relation between the evolution of tissue-specific splicing and YCAY clusters, we compared the brain-specific splicing of Nova-regulated exons in zebrafish, chicken, and mouse. The presence of YCAY clusters in lower vertebrates invariably predicted conservation of brain-specific splicing across species, whereas their absence in lower vertebrates correlated with a loss of alternative splicing. We hypothesize that evolution of Nova-regulated splicing in higher vertebrates proceeds mainly through changes in cis-acting elements, that tissue-specific splicing might in some cases evolve in a single step corresponding to evolution of a YCAY cluster, and that the conservation level of YCAY clusters relates to the functions encoded by the regulated RNAs.

  17. Alternative mRNA Splicing in the Pathogenesis of Obesity

    Directory of Open Access Journals (Sweden)

    Chi-Ming Wong


    Full Text Available Alternative mRNA splicing is an important mechanism in expansion of proteome diversity by production of multiple protein isoforms. However, emerging evidence indicates that only a limited number of annotated protein isoforms by alternative splicing are detected, and the coding sequence of alternative splice variants usually is only slightly different from that of the canonical sequence. Nevertheless, mis-splicing is associated with a large array of human diseases. Previous reviews mainly focused on hereditary and somatic mutations in cis-acting RNA sequence elements and trans-acting splicing factors. The importance of environmental perturbations contributed to mis-splicing is not assessed. As significant changes in exon skipping and splicing factors expression levels are observed with diet-induced obesity, this review focuses on several well-known alternatively spliced metabolic factors and discusses recent advances in the regulation of the expressions of splice variants under the pathophysiological conditions of obesity. The potential of targeting the alternative mRNA mis-splicing for obesity-associated diseases therapies will also be discussed.

  18. Intronic alternative splicing regulators identified by comparative genomics in nematodes.

    Directory of Open Access Journals (Sweden)

    Jennifer L Kabat


    Full Text Available Many alternative splicing events are regulated by pentameric and hexameric intronic sequences that serve as binding sites for splicing regulatory factors. We hypothesized that intronic elements that regulate alternative splicing are under selective pressure for evolutionary conservation. Using a Wobble Aware Bulk Aligner genomic alignment of Caenorhabditis elegans and Caenorhabditis briggsae, we identified 147 alternatively spliced cassette exons that exhibit short regions of high nucleotide conservation in the introns flanking the alternative exon. In vivo experiments on the alternatively spliced let-2 gene confirm that these conserved regions can be important for alternative splicing regulation. Conserved intronic element sequences were collected into a dataset and the occurrence of each pentamer and hexamer motif was counted. We compared the frequency of pentamers and hexamers in the conserved intronic elements to a dataset of all C. elegans intron sequences in order to identify short intronic motifs that are more likely to be associated with alternative splicing. High-scoring motifs were examined for upstream or downstream preferences in introns surrounding alternative exons. Many of the high-scoring nematode pentamer and hexamer motifs correspond to known mammalian splicing regulatory sequences, such as (TGCATG, indicating that the mechanism of alternative splicing regulation is well conserved in metazoans. A comparison of the analysis of the conserved intronic elements, and analysis of the entire introns flanking these same exons, reveals that focusing on intronic conservation can increase the sensitivity of detecting putative splicing regulatory motifs. This approach also identified novel sequences whose role in splicing is under investigation and has allowed us to take a step forward in defining a catalog of splicing regulatory elements for an organism. In vivo experiments confirm that one novel high-scoring sequence from our analysis

  19. Splicing variants of porcine synphilin-1

    DEFF Research Database (Denmark)

    Larsen, Knud Erik; Madsen, Lone Bruhn; Farajzadeh, Leila


    %) and to mouse (84%) synphilin-1. Three shorter transcript variants of the synphilin-1 gene were identified, all lacking one or more exons. SNCAIP transcripts were detected in most examined organs and tissues and the highest expression was found in brain tissues and lung. Conserved splicing variants and a novel...... splice form of synhilin-1 were found in this study. All synphilin-1 isoforms encoded by the identified transcript variants lack functional domains important for protein degradation....... with α-synuclein in LBs. The aim of this study was to isolate and characterize porcine synphilin-1 and isoforms hereof with the future perspective to use the pig as a model for Parkinson's disease. The porcine SNCAIP cDNA was cloned by reverse transcriptase PCR. The spatial expression of SNCAIP mRNA...

  20. Resolving deconvolution ambiguity in gene alternative splicing

    Directory of Open Access Journals (Sweden)

    Hubbell Earl


    Full Text Available Abstract Background For many gene structures it is impossible to resolve intensity data uniquely to establish abundances of splice variants. This was empirically noted by Wang et al. in which it was called a "degeneracy problem". The ambiguity results from an ill-posed problem where additional information is needed in order to obtain an unique answer in splice variant deconvolution. Results In this paper, we analyze the situations under which the problem occurs and perform a rigorous mathematical study which gives necessary and sufficient conditions on how many and what type of constraints are needed to resolve all ambiguity. This analysis is generally applicable to matrix models of splice variants. We explore the proposal that probe sequence information may provide sufficient additional constraints to resolve real-world instances. However, probe behavior cannot be predicted with sufficient accuracy by any existing probe sequence model, and so we present a Bayesian framework for estimating variant abundances by incorporating the prediction uncertainty from the micro-model of probe responsiveness into the macro-model of probe intensities. Conclusion The matrix analysis of constraints provides a tool for detecting real-world instances in which additional constraints may be necessary to resolve splice variants. While purely mathematical constraints can be stated without error, real-world constraints may themselves be poorly resolved. Our Bayesian framework provides a generic solution to the problem of uniquely estimating transcript abundances given additional constraints that themselves may be uncertain, such as regression fit to probe sequence models. We demonstrate the efficacy of it by extensive simulations as well as various biological data.

  1. DNA computing based on splicing: universality results. (United States)

    Csuhaj-Varjú, E; Freund, R; Kari, L; Păun, G


    The paper extends some of the most recently obtained results on the computational universality of specific variants of H systems (e.g. with regular sets of rules) and proves that we can construct universal computers based on various types of H systems with a finite set of splicing rules as well as a finite set of axioms, i.e. we show the theoretical possibility to design programmable universal DNA computers based on the splicing operation. For H systems working in the multiset style (where the numbers of copies of all available strings are counted) we elaborate how a Turing machine computing a partial recursive function can be simulated by an equivalent H system computing the same function; in that way, from a universal Turning machine we obtain a universal H system. Considering H systems as language generating devices we have to add various simple control mechanisms (checking the presence/absence of certain symbols in the spliced strings) to systems with a finite set of splicing rules as well as with a finite set of axioms in order to obtain the full computational power, i.e. to get a characterization of the family of recursively enumerable languages. We also introduce test tube systems, where several H systems work in parallel in their tubes and from time to time the contents of each tube are redistributed to all tubes according to certain separation conditions. By the construction of universal test tube systems we show that also such systems could serve as the theoretical basis for the development of biological (DNA) computers.

  2. Stochastic principles governing alternative splicing of RNA.


    Jianfei Hu; Eli Boritz; William Wylie; Daniel C Douek


    Author summary Alternative RNA splicing within eukaryotic cells enables each gene to generate multiple different mature transcripts which further encode proteins with distinct or even opposing functions. The relative frequencies of the transcript isoforms generated by a particular gene are essential to the maintenance of normal cellular physiology; however, the underlying mechanisms and principles that govern these frequencies are unknown. We analyzed the frequency distribution of all transcr...

  3. Teaching Leaders to Lead Themselves: An Emerging Leader Exercise (United States)

    Chavez, Carolyn I.; Gomez, Claudia; Valenzuela, Marcus; Perera, Yasanthi B.


    This article describes an exercise that allows students to experience and understand the importance of perception in leader emergence. Based on implicit leadership theories, this exercise asks students to provide one another with anonymous feedback about what extent they exhibit various trait-based leader behaviors. This exercise, which can be…

  4. Online Leader Training Course: Nebraska Equine Extension Leader Certification (United States)

    Cottle, Lena; D'Angelo, Nicole


    The Nebraska Equine Advancement Level Leader Certification Program is an online learning tool that clarifies principles of the Nebraska 4-H Equine Advancement Programs. Through an online Moodle course through, 4-H leaders and Extension educators are able to fulfill the certification requirement from any location before allowing youth…

  5. Team Leader System description

    Energy Technology Data Exchange (ETDEWEB)

    Evans, B.J.; Lundeen, T.F.; Moon, B.D.


    Purpose of the project is to design, develop, and demonstrate an advanced, prototype computer system to support on-site inspections. The system is a highly portable field computer with on-line access to facilities information, real-time communications, positioning information, and an electronic notebook for data capture. The Team Leader System provides an inspection team with a suite of advanced communication, data gathering, and data analysis tools and can be implemented on many PC-based hardware platforms. The suitcase unit is a transportable system for on-site support in a vehicle or at a stationary location at an inspection site; the personal unit is a wearable computer for in-facility or on-foot inspections.

  6. Leading Your Leaders (United States)

    Hale, Wayne N.


    Even though working on a problem has been your primary effort for the past year, your leadership may have heard about this once in a briefing a decade ago. Now they are basically clueless. Pretend that you are talking to your daughter's fifth-grade class. Explain how your complicated gizmo works. If possible, do not use acronyms. Define your terms. Put your work in context. Assume your leader has no idea what you do, who you work for, or what your gizmo does. That is a good place to start. Remember, taking the next century to study the problem or spending the Gross National Product to invent a new solution are probably not going to be acceptable solutions. Real engineers and technicians build real hardware that works in the real world in a reasonable manner within a reasonable time at a reasonable cost. True, skimping on time or money can cause mistakes, but folks whose gizmos are delayed unreasonably or cost more than is practical get their programs canceled, force the business into bankruptcy, or give the market over to the competition. Real engineers and technicians always consider cost and schedule in their work. Raising questions is important. However, we are in the business of doing things. Engineers and technicians are paid to get things done. Yes, you have to identify the problem, frame the design, identify the tests, perform the analysis, and assemble the hardware. But the goal is to solve the problem. Nobody ever said flying in space was easy. We make it look easy the same way that an Olympic champion makes her sport look easy: by working hard at improving performance every day. Better are the results of a well-defined test. Remember that a test on a laboratory bench is always an approximation of reality, and rules similar to those for good analysis also apply. One should always be mindful of Mechelay's rule: "It is better to be stupid than to run a stupid test." Often we try to overtest. If a piece of hardware passes an unbelievably difficult test, then

  7. Group leaders optimization algorithm (United States)

    Daskin, Anmer; Kais, Sabre


    We present a new global optimization algorithm in which the influence of the leaders in social groups is used as an inspiration for the evolutionary technique which is designed into a group architecture. To demonstrate the efficiency of the method, a standard suite of single and multi-dimensional optimization functions along with the energies and the geometric structures of Lennard-Jones clusters are given as well as the application of the algorithm on quantum circuit design problems. We show that as an improvement over previous methods, the algorithm scales as N 2.5 for the Lennard-Jones clusters of N-particles. In addition, an efficient circuit design is shown for a two-qubit Grover search algorithm which is a quantum algorithm providing quadratic speedup over the classical counterpart.

  8. Splicing modulation therapy in the treatment of genetic diseases

    Directory of Open Access Journals (Sweden)

    Arechavala-Gomeza V


    Full Text Available Virginia Arechavala-Gomeza,1 Bernard Khoo,2 Annemieke Aartsma-Rus3 1Neuromuscular Disorders Group, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain; 2Endocrinology, Division of Medicine, University College London, London, UK; 3Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands All authors contributed equally to this manuscript Abstract: Antisense-mediated splicing modulation is a tool that can be exploited in several ways to provide a potential therapy for rare genetic diseases. This approach is currently being tested in clinical trials for Duchenne muscular dystrophy and spinal muscular atrophy. The present review outlines the versatility of the approach to correct cryptic splicing, modulate alternative splicing, restore the open reading frame, and induce protein knockdown, providing examples of each. Finally, we outline a possible path forward toward the clinical application of this approach for a wide variety of inherited rare diseases. Keywords: splicing, therapy, antisense oligonucleotides, cryptic splicing, alternative splicing

  9. The emerging role of alternative splicing in senescence and aging. (United States)

    Deschênes, Mathieu; Chabot, Benoit


    Deregulation of precursor mRNA splicing is associated with many illnesses and has been linked to age-related chronic diseases. Here we review recent progress documenting how defects in the machinery that performs intron removal and controls splice site selection contribute to cellular senescence and organismal aging. We discuss the functional association linking p53, IGF-1, SIRT1, and ING-1 splice variants with senescence and aging, and review a selection of splicing defects occurring in accelerated aging (progeria), vascular aging, and Alzheimer's disease. Overall, it is becoming increasingly clear that changes in the activity of splicing factors and in the production of key splice variants can impact cellular senescence and the aging phenotype. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  10. Accumulation of GC donor splice signals in mammals

    Directory of Open Access Journals (Sweden)

    Koonin Eugene V


    Full Text Available Abstract The GT dinucleotide in the first two intron positions is the most conserved element of the U2 donor splice signals. However, in a small fraction of donor sites, GT is replaced by GC. A substantial enrichment of GC in donor sites of alternatively spliced genes has been observed previously in human, nematode and Arabidopsis, suggesting that GC signals are important for regulation of alternative splicing. We used parsimony analysis to reconstruct evolution of donor splice sites and inferred 298 GT > GC conversion events compared to 40 GC > GT conversion events in primate and rodent genomes. Thus, there was substantive accumulation of GC donor splice sites during the evolution of mammals. Accumulation of GC sites might have been driven by selection for alternative splicing. Reviewers This article was reviewed by Jerzy Jurka and Anton Nekrutenko. For the full reviews, please go to the Reviewers' Reports section.

  11. Nematode-Trapping Fungi. (United States)

    Jiang, Xiangzhi; Xiang, Meichun; Liu, Xingzhong


    Nematode-trapping fungi are a unique and intriguing group of carnivorous microorganisms that can trap and digest nematodes by means of specialized trapping structures. They can develop diverse trapping devices, such as adhesive hyphae, adhesive knobs, adhesive networks, constricting rings, and nonconstricting rings. Nematode-trapping fungi have been found in all regions of the world, from the tropics to Antarctica, from terrestrial to aquatic ecosystems. They play an important ecological role in regulating nematode dynamics in soil. Molecular phylogenetic studies have shown that the majority of nematode-trapping fungi belong to a monophyletic group in the order Orbiliales (Ascomycota). Nematode-trapping fungi serve as an excellent model system for understanding fungal evolution and interaction between fungi and nematodes. With the development of molecular techniques and genome sequencing, their evolutionary origins and divergence, and the mechanisms underlying fungus-nematode interactions have been well studied. In recent decades, an increasing concern about the environmental hazards of using chemical nematicides has led to the application of these biological control agents as a rapidly developing component of crop protection.

  12. Splicing Express: a software suite for alternative splicing analysis using next-generation sequencing data

    Directory of Open Access Journals (Sweden)

    Jose E. Kroll


    Full Text Available Motivation. Alternative splicing events (ASEs are prevalent in the transcriptome of eukaryotic species and are known to influence many biological phenomena. The identification and quantification of these events are crucial for a better understanding of biological processes. Next-generation DNA sequencing technologies have allowed deep characterization of transcriptomes and made it possible to address these issues. ASEs analysis, however, represents a challenging task especially when many different samples need to be compared. Some popular tools for the analysis of ASEs are known to report thousands of events without annotations and/or graphical representations. A new tool for the identification and visualization of ASEs is here described, which can be used by biologists without a solid bioinformatics background.Results. A software suite named Splicing Express was created to perform ASEs analysis from transcriptome sequencing data derived from next-generation DNA sequencing platforms. Its major goal is to serve the needs of biomedical researchers who do not have bioinformatics skills. Splicing Express performs automatic annotation of transcriptome data (GTF files using gene coordinates available from the UCSC genome browser and allows the analysis of data from all available species. The identification of ASEs is done by a known algorithm previously implemented in another tool named Splooce. As a final result, Splicing Express creates a set of HTML files composed of graphics and tables designed to describe the expression profile of ASEs among all analyzed samples. By using RNA-Seq data from the Illumina Human Body Map and the Rat Body Map, we show that Splicing Express is able to perform all tasks in a straightforward way, identifying well-known specific events.Availability and Implementation.Splicing Express is written in Perl and is suitable to run only in UNIX-like systems. More details can be found at:

  13. Identification of common genetic variation that modulates alternative splicing.

    Directory of Open Access Journals (Sweden)

    Jeremy Hull


    Full Text Available Alternative splicing of genes is an efficient means of generating variation in protein function. Several disease states have been associated with rare genetic variants that affect splicing patterns. Conversely, splicing efficiency of some genes is known to vary between individuals without apparent ill effects. What is not clear is whether commonly observed phenotypic variation in splicing patterns, and hence potential variation in protein function, is to a significant extent determined by naturally occurring DNA sequence variation and in particular by single nucleotide polymorphisms (SNPs. In this study, we surveyed the splicing patterns of 250 exons in 22 individuals who had been previously genotyped by the International HapMap Project. We identified 70 simple cassette exon alternative splicing events in our experimental system; for six of these, we detected consistent differences in splicing pattern between individuals, with a highly significant association between splice phenotype and neighbouring SNPs. Remarkably, for five out of six of these events, the strongest correlation was found with the SNP closest to the intron-exon boundary, although the distance between these SNPs and the intron-exon boundary ranged from 2 bp to greater than 1,000 bp. Two of these SNPs were further investigated using a minigene splicing system, and in each case the SNPs were found to exert cis-acting effects on exon splicing efficiency in vitro. The functional consequences of these SNPs could not be predicted using bioinformatic algorithms. Our findings suggest that phenotypic variation in splicing patterns is determined by the presence of SNPs within flanking introns or exons. Effects on splicing may represent an important mechanism by which SNPs influence gene function.

  14. Alternative Splicing of FOXP3-Virtue and Vice. (United States)

    Mailer, Reiner K W


    FOXP3 is the lineage-defining transcription factor of CD4+ CD25+ regulatory T cells. While many aspects of its regulation, interaction, and function are conserved among species, alternatively spliced FOXP3 isoforms are expressed only in human cells. This review summarizes current knowledge about alternative splicing of FOXP3 and the specific functions of FOXP3 isoforms in health and disease. Future perspectives in research and the therapeutic potential of manipulating alternative splicing of FOXP3 are discussed.

  15. Tartus alustas tegevust LEADER infokeskus

    Index Scriptorium Estoniae


    Tartus alustas tegevust LEADER infokeskus, mille eesmärk on informeerida ja nõustada maakondade omavalitsustöötajate, ettevõtjate ning MTÜde esindajaid, kes on huvitatud Eesti riikliku arengukava meetme "Kohaliku initsiatiivi arendamine - LEADER-tüüpi meetme raames toetuse saamisest ning selleks vajalike partnerlusel põhinevate kohalike tegevusgruppide loomisest"

  16. From the Field: Learning Leaders (United States)

    Weigel, Kathleen; Jones, Richard


    Leadership is essential to successful schools. One of the ways to support effective school leadership is to share ideas and best practices to address the common challenges faced by school leaders. This question and response format addresses common challenges and questions from practicing school leaders in the manner that a mentor might respond to…

  17. Nerio: Leader Election and Edict Ordering


    van Renesse, Robbert; Schneider, Fred B.; Gehrke, Johannes


    Coordination in a distributed system is facilitated if there is a unique process, the leader, to manage the other processes. The leader creates edicts and sends them to other processes for execution or forwarding to other processes. The leader may fail, and when this occurs a leader election protocol selects a replacement. This paper describes Nerio, a class of such leader election protocols.

  18. Systematic Analysis of Splice-Site-Creating Mutations in Cancer

    Directory of Open Access Journals (Sweden)

    Reyka G. Jayasinghe


    Full Text Available Summary: For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function. Notably, we found that neoantigens induced by SCMs are likely several folds more immunogenic compared to missense mutations, exemplified by the recurrent GATA3 SCM. Further, high expression of PD-1 and PD-L1 was observed in tumors with SCMs, suggesting candidates for immune blockade therapy. Our work highlights the importance of integrating DNA and RNA data for understanding the functional and the clinical implications of mutations in human diseases. : Jayasinghe et al. identify nearly 2,000 splice-site-creating mutations (SCMs from over 8,000 tumor samples across 33 cancer types. They provide a more accurate interpretation of previously mis-annotated mutations, highlighting the importance of integrating data types to understand the functional and the clinical implications of splicing mutations in human disease. Keywords: splicing, RNA, mutations of clinical relevance

  19. Ethical leader behavior and leader effectiveness: the role of prototypicality and trust

    NARCIS (Netherlands)

    Kalshoven, K.; den Hartog, D.N.


    The study examines factors that mediate the impact of ethical leader behavior on leader effectiveness. Little is known about how ethical leadership impacts leader effectiveness. We hypothesized that prototypicality and trust sequentially mediate the relationship between ethical leader behavior and

  20. Microfabricated Waveguide Atom Traps.

    Energy Technology Data Exchange (ETDEWEB)

    Jau, Yuan-Yu [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    A nanoscale , microfabricated waveguide structure can in - principle be used to trap atoms in well - defined locations and enable strong photon-atom interactions . A neutral - atom platform based on this microfabrication technology will be prealigned , which is especially important for quantum - control applications. At present, there is still no reported demonstration of evanescent - field atom trapping using a microfabricated waveguide structure. We described the capabilities established by our team for future development of the waveguide atom - trapping technology at SNL and report our studies to overcome the technical challenges of loading cold atoms into the waveguide atom traps, efficient and broadband optical coupling to a waveguide, and the waveguide material for high - power optical transmission. From the atomic - physics and the waveguide modeling, w e have shown that a square nano-waveguide can be utilized t o achieve better atomic spin squeezing than using a nanofiber for first time.

  1. Ion Trap Quantum Computing (United States)


    stored ions,” Adv. Atom Mol. Phys., vol. Volume 3, pp. 53–72 1968. [48] P. H. Dawson, Quadrupole Mass Spectometry and Its Applications, Melville, NY... DATE December 2011 3. REPORT TYPE AND DATES COVERED Master’s Thesis 4. TITLE AND SUBTITLE Ion trap Quantum Computing 5. FUNDING NUMBERS 6...researcher [30] that introduced the concept of ion traps in the 1950s. His experiments focused on separating atoms with different masses in order to

  2. Search For Trapped Antihydrogen

    CERN Document Server

    Andresen, Gorm B.; Baquero-Ruiz, Marcelo; Bertsche, William; Bowe, Paul D.; Bray, Crystal C.; Butler, Eoin; Cesar, Claudio L.; Chapman, Steven; Charlton, Michael; Fajans, Joel; Friesen, Tim; Fujiwara, Makoto C.; Gill, David R.; Hangst, Jeffrey S.; Hardy, Walter N.; Hayano, Ryugo S.; Hayden, Michael E.; Humphries, Andrew J.; Hydomako, Richard; Jonsell, Svante; Jorgensen, Lars V.; Kurchaninov, Lenoid; Lambo, Ricardo; Madsen, Niels; Menary, Scott; Nolan, Paul; Olchanski, Konstantin; Olin, Art; Povilus, Alexander; Pusa, Petteri; Robicheaux, Francis; Sarid, Eli; Nasr, Sarah Seif El; Silveira, Daniel M.; So, Chukman; Storey, James W.; Thompson, Robert I.; van der Werf, Dirk P.; Wilding, Dean; Wurtele, Jonathan S.; Yamazaki, Yasunori


    We present the results of an experiment to search for trapped antihydrogen atoms with the ALPHA antihydrogen trap at the CERN Antiproton Decelerator. Sensitive diagnostics of the temperatures, sizes, and densities of the trapped antiproton and positron plasmas have been developed, which in turn permitted development of techniques to precisely and reproducibly control the initial experimental parameters. The use of a position-sensitive annihilation vertex detector, together with the capability of controllably quenching the superconducting magnetic minimum trap, enabled us to carry out a high-sensitivity and low-background search for trapped synthesised antihydrogen atoms. We aim to identify the annihilations of antihydrogen atoms held for at least 130 ms in the trap before being released over ~30 ms. After a three-week experimental run in 2009 involving mixing of 10^7 antiprotons with 1.3 10^9 positrons to produce 6 10^5 antihydrogen atoms, we have identified six antiproton annihilation events that are consist...

  3. Pre-mRNA Splicing in Plants: In Vivo Functions of RNA-Binding Proteins Implicated in the Splicing Process

    Directory of Open Access Journals (Sweden)

    Katja Meyer


    Full Text Available Alternative pre-messenger RNA splicing in higher plants emerges as an important layer of regulation upon exposure to exogenous and endogenous cues. Accordingly, mutants defective in RNA-binding proteins predicted to function in the splicing process show severe phenotypic alterations. Among those are developmental defects, impaired responses to pathogen threat or abiotic stress factors, and misregulation of the circadian timing system. A suite of splicing factors has been identified in the model plant Arabidopsis thaliana. Here we summarize recent insights on how defects in these splicing factors impair plant performance.

  4. Identification of cis-acting elements and splicing factors involved in the regulation of BIM Pre-mRNA splicing. (United States)

    Juan, Wen Chun; Roca, Xavier; Ong, S Tiong


    Aberrant changes in the expression of the pro-apoptotic protein, BCL-2-like 11 (BIM), can result in either impaired or excessive apoptosis, which can contribute to tumorigenesis and degenerative disorders, respectively. Altering BIM pre-mRNA splicing is an attractive approach to modulate apoptosis because BIM activity is partly determined by the alternative splicing of exons 3 or 4, whereby exon 3-containing transcripts are not apoptotic. Here we identified several cis-acting elements and splicing factors involved in BIM alternative splicing, as a step to better understand the regulation of BIM expression. We analyzed a recently discovered 2,903-bp deletion polymorphism within BIM intron 2 that biased splicing towards exon 3, and which also impaired BIM-dependent apoptosis. We found that this region harbors multiple redundant cis-acting elements that repress exon 3 inclusion. Furthermore, we have isolated a 23-nt intronic splicing silencer at the 3' end of the deletion that is important for excluding exon 3. We also show that PTBP1 and hnRNP C repress exon 3 inclusion, and that downregulation of PTBP1 inhibited BIM-mediated apoptosis. Collectively, these findings start building our understanding of the cis-acting elements and splicing factors that regulate BIM alternative splicing, and also suggest potential approaches to alter BIM splicing for therapeutic purposes.

  5. Alternative splicing enriched cDNA libraries identify breast cancer-associated transcripts (United States)


    Background Alternative splicing (AS) is a central mechanism in the generation of genomic complexity and is a major contributor to transcriptome and proteome diversity. Alterations of the splicing process can lead to deregulation of crucial cellular processes and have been associated with a large spectrum of human diseases. Cancer-associated transcripts are potential molecular markers and may contribute to the development of more accurate diagnostic and prognostic methods and also serve as therapeutic targets. Alternative splicing-enriched cDNA libraries have been used to explore the variability generated by alternative splicing. In this study, by combining the use of trapping heteroduplexes and RNA amplification, we developed a powerful approach that enables transcriptome-wide exploration of the AS repertoire for identifying AS variants associated with breast tumor cells modulated by ERBB2 (HER-2/neu) oncogene expression. Results The human breast cell line (C5.2) and a pool of 5 ERBB2 over-expressing breast tumor samples were used independently for the construction of two AS-enriched libraries. In total, 2,048 partial cDNA sequences were obtained, revealing 214 alternative splicing sequence-enriched tags (ASSETs). A subset with 79 multiple exon ASSETs was compared to public databases and reported 138 different AS events. A high success rate of RT-PCR validation (94.5%) was obtained, and 2 novel AS events were identified. The influence of ERBB2-mediated expression on AS regulation was evaluated by capillary electrophoresis and probe-ligation approaches in two mammary cell lines (Hb4a and C5.2) expressing different levels of ERBB2. The relative expression balance between AS variants from 3 genes was differentially modulated by ERBB2 in this model system. Conclusions In this study, we presented a method for exploring AS from any RNA source in a transcriptome-wide format, which can be directly easily adapted to next generation sequencers. We identified AS transcripts

  6. Transcription rate strongly affects splicing fidelity and cotranscriptionality in budding yeast


    Aslanzadeh, Vahid; Huang, Yuanhua; Sanguinetti, Guido; Beggs, Jean D.


    The functional consequences of alternative splicing on altering the transcription rate have been the subject of intensive study in mammalian cells but less is known about effects of splicing on changing the transcription rate in yeast. We present several lines of evidence showing that slow RNA polymerase II elongation increases both cotranscriptional splicing and splicing efficiency and that faster elongation reduces cotranscriptional splicing and splicing efficiency in budding yeast, suggest...

  7. Remembering the Leaders of China. (United States)

    Fu, Mingchen; Xue, Yan; DeSoto, K Andrew; Yuan, Ti-Fei


    In two studies, we examined Chinese students' memory for the names of the leaders of China. In Study 1, subjects were cued with the names of periods from China's history. Subjects listed as many leaders as possible from each period and put them in the correct ordinal position when they could (see Roediger and DeSoto, 2014). Results showed that within each period, a primacy effect and sometimes a recency effect emerged. Moreover, the average recall probability for leaders within a specific period was a function of the ordinal position of the period. In Study 2, we asked another group of subjects to identify the sources through which they were able to recall each leader. We found that most subjects remembered leaders due to class and coursework. We also found a relation between a leader's recall probability and the amount of information available on that leader on the Internet. Our findings further imply that the serial position function captures the form of collective memory.

  8. Evolution of alternative splicing regulation: changes in predicted exonic splicing regulators are not associated with changes in alternative splicing levels in primates

    DEFF Research Database (Denmark)

    Irimia, Manuel; Rukov, Jakob Lewin; Roy, Scott William


    of interspecific differences in these elements on the evolution of alternative splicing levels has not yet been investigated at genomic level. Here we study the effect of interspecific differences in predicted exonic splicing regulators (ESRs) on exon inclusion levels in human and chimpanzee. For this purpose, we...... compiled and studied comprehensive datasets of predicted ESRs, identified by several computational and experimental approaches, as well as microarray data for changes in alternative splicing levels between human and chimpanzee. Surprisingly, we found no association between changes in predicted ESRs...

  9. RNA Splicing: Regulation and Dysregulation in the Heart

    NARCIS (Netherlands)

    van den Hoogenhof, Maarten M. G.; Pinto, Yigal M.; Creemers, Esther E.


    RNA splicing represents a post-transcriptional mechanism to generate multiple functional RNAs or proteins from a single transcript. The evolution of RNA splicing is a prime example of the Darwinian function follows form concept. A mutation that leads to a new mRNA (form) that encodes for a new

  10. Revealing the Determinants of Widespread Alternative Splicing Perturbation in Cancer

    Directory of Open Access Journals (Sweden)

    Yongsheng Li


    Full Text Available It is increasingly appreciated that alternative splicing plays a key role in generating functional specificity and diversity in cancer. However, the mechanisms by which cancer mutations perturb splicing remain unknown. Here, we developed a network-based strategy, DrAS-Net, to investigate more than 2.5 million variants across cancer types and link somatic mutations with cancer-specific splicing events. We identified more than 40,000 driver variant candidates and their 80,000 putative splicing targets deregulated in 33 cancer types and inferred their functional impact. Strikingly, tumors with splicing perturbations show reduced expression of immune system-related genes and increased expression of cell proliferation markers. Tumors harboring different mutations in the same gene often exhibit distinct splicing perturbations. Further stratification of 10,000 patients based on their mutation-splicing relationships identifies subtypes with distinct clinical features, including survival rates. Our work reveals how single-nucleotide changes can alter the repertoires of splicing isoforms, providing insights into oncogenic mechanisms for precision medicine.

  11. ASpedia: a comprehensive encyclopedia of human alternative splicing. (United States)

    Hyung, Daejin; Kim, Jihyun; Cho, Soo Young; Park, Charny


    Alternative splicing confers the human genome complexity by increasing the diversity of expressed mRNAs. Hundreds or thousands of splicing regions have been identified through differential alternative splicing analysis of high-throughput datasets. However, it is hard to explain the functional impact of each splicing event. Protein domain formation and nonsense-mediated decay are considered the main functional features of splicing. However, other functional features such as miRNA target sites, phosphorylation sites and single-nucleotide variations are directly affected by alternative splicing and affect downstream function. Hence, we established ASpedia: a comprehensive database for human alternative splicing annotation, which encompasses a range of functions, from genomic annotation to isoform-specific function (ASpedia, The database provides three features: (i) genomic annotation extracted from DNA, RNA and proteins; (ii) transcription and regulation elements analyzed from next-generation sequencing datasets; and (iii) isoform-specific functions collected from known and published datasets. The ASpedia web application includes three components: an annotation database, a retrieval system and a browser specialized in the identification of human alternative splicing events. The retrieval system supports multiple AS event searches resulting from high-throughput analysis and the AS browser comprises genome tracks. Thus, ASpedia facilitates the systemic annotation of the functional impacts of multiple AS events. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Quantitative regulation of alternative splicing in evolution and development

    DEFF Research Database (Denmark)

    Irimia, Manuel; Rukov, Jakob L; Roy, Scott W


    Alternative splicing (AS) is a widespread mechanism with an important role in increasing transcriptome and proteome diversity by generating multiple different products from the same gene. Evolutionary studies of AS have focused primarily on the conservation of alternatively spliced sequences or o...

  13. Antihydrogen formation and trapping

    CERN Document Server

    Madsen, Niels


    Antihydrogen, the bound state of a positron and an antiproton, is the only neutral pure antimatter system available to date, and as such provides an excellent testbed for probing fundamental symmetries between matter and antimatter. In this chapter we will concentrate on the physics issues that were addressed in order to achieve the first trapping of antihydrogen. Antihydrogen can be created by merging antiprotons and positrons in a Penning–Malmberg trap. However, traps for antihydrogen are at best about ∼50 μeV deep and, as no readily available cooling techniques exist, the antihydrogen must be formed trapped. Antiprotons are sourced from an accelerator and arrive with a typical energy of 5.3 MeV. The large numbers of positrons needed means that the self-potential of the positrons are of order 2–5 V. With such energetic ingredients a range of plasma control and diagnostic techniques must be brought to bear on the particles to succeed in making any antihydrogen cold enough to be trapped.

  14. Splice Site Mutations in the ATP7A Gene

    DEFF Research Database (Denmark)

    Skjørringe, Tina; Tümer, Zeynep; Møller, Lisbeth Birk


    Menkes disease (MD) is caused by mutations in the ATP7A gene. We describe 33 novel splice site mutations detected in patients with MD or the milder phenotypic form, Occipital Horn Syndrome. We review these 33 mutations together with 28 previously published splice site mutations. We investigate 12...... mutations for their effect on the mRNA transcript in vivo. Transcriptional data from another 16 mutations were collected from the literature. The theoretical consequences of splice site mutations, predicted with the bioinformatics tool Human Splice Finder, were investigated and evaluated in relation...... to in vivo results. Ninety-six percent of the mutations identified in 45 patients with classical MD were predicted to have a significant effect on splicing, which concurs with the absence of any detectable wild-type transcript in all 19 patients investigated in vivo. Sixty-seven percent of the mutations...

  15. A study of alternative splicing in the pig

    DEFF Research Database (Denmark)

    Hillig, Ann-Britt Nygaard; Cirera Salicio, Susanna; Gilchrist, Michael J.


    BACKGROUND: Since at least half of the genes in mammalian genomes are subjected to alternative splicing, alternative pre-mRNA splicing plays an important contribution to the complexity of the mammalian proteome. Expressed sequence tags (ESTs) provide evidence of a great number of possible...... alternative isoforms. With the EST resource for the domestic pig now containing more than one million porcine ESTs, it is possible to identify alternative splice forms of the individual transcripts in this species from the EST data with some confidence. RESULTS: The pig EST data generated by the Sino...... transcripts with expression patterns matching those of the EST data. The remaining four genes had tissue-restricted expression of alternative spliced transcripts. Five out of the 16 splice events that were experimentally verified were found to be putative pig specific. CONCLUSIONS: In accordance with human...

  16. Detecting Image Splicing Using Merged Features in Chroma Space

    Directory of Open Access Journals (Sweden)

    Bo Xu


    Full Text Available Image splicing is an image editing method to copy a part of an image and paste it onto another image, and it is commonly followed by postprocessing such as local/global blurring, compression, and resizing. To detect this kind of forgery, the image rich models, a feature set successfully used in the steganalysis is evaluated on the splicing image dataset at first, and the dominant submodel is selected as the first kind of feature. The selected feature and the DCT Markov features are used together to detect splicing forgery in the chroma channel, which is convinced effective in splicing detection. The experimental results indicate that the proposed method can detect splicing forgeries with lower error rate compared to the previous literature.

  17. Some relations between two stages DNA splicing languages (United States)

    Mudaber, Mohammad Hassan; Yusof, Yuhani; Mohamad, Mohd Sham


    A new symbolization of Yusof-Goode (Y-G) rule, which is associated with Y-G splicing system, was introduced by Yusof in 2012 under the framework of formal language theory. The purpose of this investigation is to present the biological process of DNA splicing in a translucent way. In this study, two stages splicing languages are introduced based on Y-G approach and some relations between stage one and stage two splicing languages are presented, given as theorems. Additionally, the existing relations between two stages splicing languages based on crossings and contexts of restriction enzymes factors with respect to two initial strings (having two cutting sites) and two rules are presented as subset.

  18. Employees' Perceptions of Their Leaders

    Directory of Open Access Journals (Sweden)

    Golubović-Stojanović Aleksandra


    Full Text Available This paper presents the research about employees and the leaders who are included in leading the organization, as an important segment of the modern business. The aim of this research is to show the real picture about presence new strategies of leaders in the organizations, as well as the analysis of the perception of employees about their leaders. The research in business organizations conducted on the sample of leaders and employees. The construction of high-quality questionnaire represents the important segment of modern statistical and business researches. The issues in questionnaire construction are very complex and they are in the focus of all statistical and research methodologies. It was conducted on the sample of at least 250 examinees (employees in bigger companies in Serbia. Research results showed that understanding communication satisfaction, with its link to job satisfaction, should provide an ability to better target resources to improve communication satisfaction issues.

  19. Teambuilding: A Strategic Leader Imperative

    National Research Council Canada - National Science Library

    Putko, Christopher J


    .... An Army Training and Leader Development Panel (ATLDP) - 2001 cited team building components in need of improvement to include command climate empowerment of subordinates, mentorship, counseling, accountability, and feedback...

  20. SpliceDetector: a software for detection of alternative splicing events in human and model organisms directly from transcript IDs. (United States)

    Baharlou Houreh, Mandana; Ghorbani Kalkhajeh, Payam; Niazi, Ali; Ebrahimi, Faezeh; Ebrahimie, Esmaeil


    In eukaryotes, different combinations of exons lead to multiple transcripts with various functions in protein level, in a process called alternative splicing (AS). Unfolding the complexity of functional genomics through genome-wide profiling of AS and determining the altered ultimate products provide new insights for better understanding of many biological processes, disease progress as well as drug development programs to target harmful splicing variants. The current available tools of alternative splicing work with raw data and include heavy computation. In particular, there is a shortcoming in tools to discover AS events directly from transcripts. Here, we developed a Windows-based user-friendly tool for identifying AS events from transcripts without the need to any advanced computer skill or database download. Meanwhile, due to online working mode, our application employs the updated SpliceGraphs without the need to any resource updating. First, SpliceGraph forms based on the frequency of active splice sites in pre-mRNA. Then, the presented approach compares query transcript exons to SpliceGraph exons. The tool provides the possibility of statistical analysis of AS events as well as AS visualization compared to SpliceGraph. The developed application works for transcript sets in human and model organisms.

  1. Remembering the Leaders of China

    Directory of Open Access Journals (Sweden)

    Mingchen eFu


    Full Text Available In two studies, we examined Chinese students’ memory for the names of the leaders of China. In Study 1, subjects were cued with the names of periods from China’s history. Subjects listed as many leaders as possible from each period and put them in the correct ordinal position when they could (see Roediger & DeSoto, 2014. Results showed that within each period, a primacy effect and sometimes a recency effect emerged. Moreover, the average recall probability for leaders within a specific period was a function of the ordinal position of the period. In Study 2, we asked another group of subjects to identify the sources through which they were able to recall each leader. We found that most subjects remembered leaders thanks to class and coursework. We also found a relation between a leader’s recall probability and the amount of information available on that leader on the Internet. Our findings further imply that the serial position function captures the form of collective memory.

  2. Thermoelectrically cooled water trap (United States)

    Micheels, Ronald H [Concord, MA


    A water trap system based on a thermoelectric cooling device is employed to remove a major fraction of the water from air samples, prior to analysis of these samples for chemical composition, by a variety of analytical techniques where water vapor interferes with the measurement process. These analytical techniques include infrared spectroscopy, mass spectrometry, ion mobility spectrometry and gas chromatography. The thermoelectric system for trapping water present in air samples can substantially improve detection sensitivity in these analytical techniques when it is necessary to measure trace analytes with concentrations in the ppm (parts per million) or ppb (parts per billion) partial pressure range. The thermoelectric trap design is compact and amenable to use in a portable gas monitoring instrumentation.

  3. What Is an Innovative Educational Leader? (United States)

    Marron, Joseph M.; Cunniff, Dan


    This paper outlined the traits of an innovative educational leader in our changing society. It discussed the difference in a manager and leader, as well as the specific dispositions that differentiate the innovative educational leader from what many consider the average leader. The authors used the acronym "HELPSS" to highlight the…

  4. Splicing Express: a software suite for alternative splicing analysis using next-generation sequencing data


    Kroll, Jose E.; Kim, Jihoon; Ohno-Machado, Lucila; de Souza, Sandro J.


    Motivation. Alternative splicing events (ASEs) are prevalent in the transcriptome of eukaryotic species and are known to influence many biological phenomena. The identification and quantification of these events are crucial for a better understanding of biological processes. Next-generation DNA sequencing technologies have allowed deep characterization of transcriptomes and made it possible to address these issues. ASEs analysis, however, represents a challenging task especially when many dif...

  5. Redesigning octopus traps

    Directory of Open Access Journals (Sweden)

    Eduarda Gomes


    In order to minimise the identified problems in the actual traps, the present work proposes a new design with the aim of reducing the volume and weight during transport, and also during onshore storage. Alternative materials to avoid corrosion and formation of encrustations were also proposed.

  6. Global Splicing Pattern Reversion during Somatic Cell Reprogramming

    Directory of Open Access Journals (Sweden)

    Sho Ohta


    Full Text Available Alternative splicing generates multiple transcripts from a single gene, and cell-type-specific splicing profiles are important for the properties and functions of the cells. Recently, somatic cells have been shown to undergo dedifferentiation after the forced expression of transcription factors. However, it remains unclear whether somatic cell splicing is reorganized during reprogramming. Here, by combining deep sequencing with high-throughput absolute qRT-PCR, we show that somatic splicing profiles revert to pluripotent ones during reprogramming. Remarkably, the splicing pattern in pluripotent stem cells resembles that in testes, and the regulatory regions have specific characteristics in length and sequence. Furthermore, our siRNA screen has identified RNA-binding proteins that regulate splicing events in iPSCs. We have then demonstrated that two of the RNA-binding proteins, U2af1 and Srsf3, play a role in somatic cell reprogramming. Our results indicate that the drastic alteration in splicing represents part of the molecular network involved in the reprogramming process.

  7. Herboxidiene triggers splicing repression and abiotic stress responses in plants

    KAUST Repository

    Alshareef, Sahar


    Background Constitutive and alternative splicing of pre-mRNAs from multiexonic genes controls the diversity of the proteome; these precisely regulated processes also fine-tune responses to cues related to growth, development, and stresses. Small-molecule inhibitors that perturb splicing provide invaluable tools for use as chemical probes to uncover the molecular underpinnings of splicing regulation and as potential anticancer compounds. Results Here, we show that herboxidiene (GEX1A) inhibits both constitutive and alternative splicing. Moreover, GEX1A activates genome-wide transcriptional patterns involved in abiotic stress responses in plants. GEX1A treatment -activated ABA-inducible promoters, and led to stomatal closure. Interestingly, GEX1A and pladienolide B (PB) elicited similar cellular changes, including alterations in the patterns of transcription and splicing, suggesting that these compounds might target the same spliceosome complex in plant cells. Conclusions Our study establishes GEX1A as a potent splicing inhibitor in plants that can be used to probe the assembly, dynamics, and molecular functions of the spliceosome and to study the interplay between splicing stress and abiotic stresses, as well as having potential biotechnological applications.

  8. Aberrant and alternative splicing in skeletal system disease. (United States)

    Fan, Xin; Tang, Liling


    The main function of skeletal system is to support the body and help movement. A variety of factors can lead to skeletal system disease, including age, exercise, and of course genetic makeup and expression. Pre-mRNA splicing plays a crucial role in gene expression, by creating multiple protein variants with different biological functions. The recent studies show that several skeletal system diseases are related to pre-mRNA splicing. This review focuses on the relationship between pre-mRNA splicing and skeletal system disease. On the one hand, splice site mutation that leads to aberrant splicing often causes genetic skeletal system disease, like COL1A1, SEDL and LRP5. On the other hand, alternative splicing without genomic mutation may generate some marker protein isoforms, for example, FN, VEGF and CD44. Therefore, understanding the relationship between pre-mRNA splicing and skeletal system disease will aid in uncovering the mechanism of disease and contribute to the future development of gene therapy. © 2013 Elsevier B.V. All rights reserved.

  9. Gender, Communication Styles, and Leader Effectiveness


    Timko, Krisztina


    We study gender differences in the behavior, communication, and effectiveness of randomly selected leaders in a laboratory experiment using the turnaround game. Leaders can send nonbinding pre‐play text messages to try to convince followers to coordinate on the Pareto‐efficient equilibrium. The treatment variations consist of the gender of the leader, and whether the communication is one‐way (only leaders send messages) or two‐way (first followers send messages to their leader, and subsequent...

  10. Narcissistic leaders: An asset or a liability? Leader visibility, follower responses, and group-level absenteeism. (United States)

    Nevicka, Barbara; Van Vianen, Annelies E M; De Hoogh, Annebel H B; Voorn, Bart C M


    Although narcissists often emerge as leaders, research has thus far shown inconsistent results on the relationship between leader narcissism and effectiveness in the eyes of followers. Here we draw on leader distance theory (Shamir, 1995) and implicit leader theory (Lord & Maher, 1991) to propose that followers' assessment of a narcissistic leader and followers' overall job attitudes depend on the leader's visibility to the followers. The more opportunities followers have to observe narcissistic leaders the more they will experience these leaders' toxic behavior (e.g., exploitativeness) and the less they will perceive the leader as effective. To test our hypotheses we collected multisource, longitudinal data from 175 retail stores and obtained subjective (followers' perceptions of leader effectiveness and their overall job attitudes) as well as objective (leaders' organizational experience at time of hire, employee absenteeism trends) indices of leader functionality. Results showed that narcissistic leaders had less organizational experience at the time they were hired. Moreover, when followers had fewer opportunities to observe their leader, leader narcissism was positively related to perceived leadership effectiveness and job attitudes. However, when followers had more opportunity to observe their leader, the positive relationship disappeared. Finally, leader narcissism was neither positively nor negatively associated with absenteeism, whereas absenteeism declined over time under non-narcissistic leaders. These findings advance our knowledge of how followers respond to narcissistic leaders and how these leaders function in organizational settings where they have legitimate positions of power. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  11. Trapping metastable chromium atoms in a crossed optical dipole trap (United States)

    Beaufils, Q.; Chicireanu, R.; Pouderous, A.; Laburthe-Tolra, B.; Maréchal, E.; Vernac, L.; Keller, J.-C.; Gorceix, O.

    We report the fast accumulation of up to 1 million 52Cr metastable atoms in a mixed trap formed by the superposition of a quadrupolar magnetic trap and a strongly confining optical trap. The cloud is at a temperature of 100 μK with a peak density of 1018 atoms/m3, which is a promising starting point to reach quantum degeneracy by forced evaporation in an optical trap.

  12. Oriented scanning is the leading mechanism underlying 5' splice site selection in mammals

    NARCIS (Netherlands)

    Borensztajn, Keren; Sobrier, Marie-Laure; Duquesnoy, Philippe; Fischer, Anne-Marie; Tapon-Bretaudière, Jacqueline; Amselem, Serge


    Splice site selection is a key element of pre-mRNA splicing. Although it is known to involve specific recognition of short consensus sequences by the splicing machinery, the mechanisms by which 5' splice sites are accurately identified remain controversial and incompletely resolved. The human F7

  13. A live-trap and trapping technique for fossorial mammals

    African Journals Online (AJOL)

    injuries, the trauma involved in such capture does not promote acclimatization ... involved in the evolution of trap design for use in various field conditions and live capture of other fossorial mammals are discussed. Materials and Methods. Constructing the .... work of setting traps halved by placing only one trap instead of the ...

  14. Splicing landscape of the eight collaborative cross founder strains. (United States)

    Zheng, Christina L; Wilmot, Beth; Walter, Nicole Ar; Oberbeck, Denesa; Kawane, Sunita; Searles, Robert P; McWeeney, Shannon K; Hitzemann, Robert


    The Collaborative Cross (CC) is a large panel of genetically diverse recombinant inbred mouse strains specifically designed to provide a systems genetics resource for the study of complex traits. In part, the utility of the CC stems from the extensive genome-wide annotations of founder strain sequence and structural variation. Still missing, however, are transcriptome-specific annotations of the CC founder strains that could further enhance the utility of this resource. We provide a comprehensive survey of the splicing landscape of the 8 CC founder strains by leveraging the high level of alternative splicing within the brain. Using deep transcriptome sequencing, we found that a majority of the splicing landscape is conserved among the 8 strains, with ~65% of junctions being shared by at least 2 strains. We, however, found a large number of potential strain-specific splicing events as well, with an average of ~3000 and ~500 with ≥3 and ≥10 sequence read coverage, respectively, within each strain. To better understand strain-specific splicing within the CC founder strains, we defined criteria for and identified high-confidence strain-specific splicing events. These splicing events were defined as exon-exon junctions 1) found within only one strain, 2) with a read coverage ≥10, and 3) defined by a canonical splice site. With these criteria, a total of 1509 high-confidence strain-specific splicing events were identified, with the majority found within two of the wild-derived strains, CAST and PWK. Strikingly, the overwhelming majority, 94%, of these strain-specific splicing events are not yet annotated. Strain-specific splicing was also located within genomic regions recently reported to be over- and under-represented within CC populations. Phenotypic characterization of CC populations is increasing; thus these results will not only aid in further elucidating the transcriptomic architecture of the individual CC founder strains, but they will also help in guiding

  15. Alternative splicing variations in mouse CAPS2: differential expression and functional properties of splicing variants

    Directory of Open Access Journals (Sweden)

    Furuichi Teiichi


    Full Text Available Abstract Background Ca2+-dependent activator protein 2 (CAPS2/CADPS2 is a secretory vesicle-associated protein involved in the release of neurotrophin. We recently reported that an aberrant, alternatively spliced CAPS2 mRNA that lacks exon 3 (CAPS2Δexon3 is detected in some patients with autism. Splicing variations in mouse CAPS2 and their expression and functions remain unclear. Results In this study, we defined 31 exons in the mouse CAPS2 gene and identified six alternative splicing variants, CAPS2a-f. CAPS2a is an isoform lacking exons 22 and 25, which encode part of the Munc13-1-homologous domain (MHD. CAPS2b lacks exon 25. CAPS2c lacks exons 11 and 22. CAPS2d, 2e, and 2f have C-terminal deletions from exon 14, exon 12, and exon 5, respectively. On the other hand, a mouse counterpart of CAPS2Δexon3 was not detected in the mouse tissues tested. CAPS2b was expressed exclusively in the brain, and the other isoforms were highly expressed in the brain, but also in some non-neural tissues. In the brain, all isoforms showed predominant expression patterns in the cerebellum. In the developing cerebellum, CAPS2b showed an up-regulated expression pattern, whereas the other isoforms exhibited transiently peaked expression patterns. CAPS2 proteins were mostly recovered in soluble fractions, but some were present in membrane fractions, except for CAPS2c and 2f, both of which lack the PH domain, suggesting that the PH domain is important for membrane association. In contrast to CAPS2a and 2b, CAPS2c showed slightly decreased BDNF-releasing activity, which is likely due to the C-terminal truncation of the PH domain in CAPS2c. Conclusion This study indicates that, in mouse, there are six splicing variants of CAPS2 (CAPS2a-f, and that these are subdivided into two groups: a long form containing the C-terminal MHD and a short form lacking the C-terminal MHD. These results demonstrate that the splicing variations correlate with their expression patterns and

  16. Optical trapping of gold aerosols

    DEFF Research Database (Denmark)

    Schmitt, Regina K.; Pedersen, Liselotte Jauffred; Taheri, S. M.


    Aerosol trapping has proven challenging and was only recently demonstrated.1 This was accomplished by utilizing an air chamber designed to have a minimum of turbulence and a laser beam with a minimum of aberration. Individual gold nano-particles with diameters between 80 nm and 200 nm were trapped...... in air using a 1064 nm laser. The positions visited by the trapped gold nano-particle were quantified using a quadrant photo diode placed in the back focal plane. The time traces were analyzed and the trapping stiffness characterizing gold aerosol trapping determined and compared to aerosol trapping...... of nanometer sized silica and polystyrene particles. Based on our analysis, we concluded that gold nano-particles trap more strongly in air than similarly sized polystyrene and silica particles. We found that, in a certain power range, the trapping strength of polystyrene particles is linearly decreasing...

  17. Travel opinion leaders and seekers

    DEFF Research Database (Denmark)

    Yoo, Kyung-Hyan; Gretzel, Ulrike; Zach, Florian


    While opinion leadership has been recognized as important in tourism, there has been very little empirical research investigating the phenomenon. Given new developments in social media technologies, it is especially important to understand whether travel opinion leadership and seeking are drivers...... of specific social media perceptions and behaviours. Based on an online survey of US online travellers, this paper seeks to identify travel opinion leaders and seekers and their characteristics. Further, the research conducted investigated linkages between travel opinion leadership/seeking and travel social...... media use. The findings suggest that travel opinion leadership and seeking are distinct but connected. Both opinion leaders and seekers are technology savvy, young, educated, involved in travel planning and engaged in social media use for travel. What distinguishes opinion leaders is their greater...

  18. Feedback trap using optical force (United States)

    Jun, Yonggun; Pak, Hyuk Kyu

    Recently, the feedback trap using electrophoretic force (ABEL trap) has been used in the experimental study of non-equilibrium thermodynamics such as Landauer's erasure principle. This trap can trap and manipulate a small particle in solution by canceling the Brownian fluctuations. Here, we propose a simple way to control a bead using optical force with feedback and show the dynamics of a single particle in the virtual potential.

  19. Preparing nurse leaders for 2020. (United States)

    Huston, Carol


    This article highlights eight leadership competencies likely to be an essential part of the nurse leader's repertoire in 2020. Planning for the future is difficult, even when environments are relatively static. When environments are dynamic, the challenges multiply exponentially. Unfortunately, few environments have been more unpredictable in the 21st century than health care. The healthcare system is in chaos, as is much of the business world. It is critical then that contemporary nursing and healthcare leaders identify skill sets that will be needed by nurse leaders in 2020 and begin now to create the educational models and management development programs necessary to assure these skills are present. Essential nurse leader competencies for 2020 include: (i) A global perspective or mindset regarding healthcare and professional nursing issues. (ii) Technology skills which facilitate mobility and portability of relationships, interactions, and operational processes. (iii) Expert decision-making skills rooted in empirical science. (iv) The ability to create organization cultures that permeate quality healthcare and patient/worker safety. (v) Understanding and appropriately intervening in political processes. (vi) Highly developed collaborative and team building skills. (vii) The ability to balance authenticity and performance expectations. (viii) Being able to envision and proactively adapt to a healthcare system characterized by rapid change and chaos. Nursing education programmes and healthcare organizations must be begin now to prepare nurses to be effective leaders in 2020. This will require the formal education and training that are a part of most management development programmes as well as a development of appropriate attitudes through social learning. Proactive succession planning will also be key to having nurse leaders who can respond effectively to the new challenges and opportunities that will be presented to them in 2020.

  20. Combined Logistics Officers Advanced Course (CLOAC): Leader Development for Future Ordnance Strategic Leaders

    National Research Council Canada - National Science Library

    Shipley, Claude


    Formal training is one of the methods for development of strategic leaders. The development of strategic Ordnance leaders is rooted initially with an officer first becoming competent as a leader and knowledgeable in their technical skills...

  1. Leader performance and prototypicality : Their inter-relationship and impact on leaders' identity entrepreneurship

    NARCIS (Netherlands)

    Steffens, Niklas K.; Haslam, S. Alexander; Ryan, Michelle K.; Kessler, Thomas


    Research has demonstrated that leader performance and leader prototypicality are both predictors of leader endorsement. While performance and prototypicality have generally been considered to be independent, this paper suggests that performance and prototypicality are interdependent and have a

  2. Death patterns among Nigerian leaders. (United States)

    Eze, Kenneth C; Ugochukwu, Ozoemenam M; Nzegwu, Martin A


    The aim of this study is to establish the patterns of death amongst Nigerian leaders since independence, thus providing a feasible avenue to avoid their recurrence if possible especially amongst the political elite who currently hold power. Using available unclassified authentic public information, all leaders who had ruled Nigeria since her independence on 1 October, 1960 until her 45th birthday on 1 October 2005, irrespective of whether they are dead or alive were included. Data was extracted and analyzed. On 1 October 2005, Nigeria celebrated 45 years as a sovereign nation. Within this period, the country has had eleven leaders, all of whom were men. Only three (27.3%) were civilians, while eight (72.7%) were army generals. Of the eleven leaders, four (36.4%) had died before Nigeria reached its 45th birthday and all of these four (100%) died while still in office. Three of the dead leaders (75%) were assassinated, while one (25%) died suddenly in mysterious circumstances, believed to be the result of poisoning by unknown external powerful interest groups. Three of the deaths (75%) occurred during violent periods of Nigeria's checkered history (1966-1970 and 1993-1999), showing that periods of national and international strife appeared to be the weakest link in chains of events that led to their death while in office. Autopsies were neither requested nor performed on any of the dead leaders, signifying an entrenched culture of nonchalance, a lack of a coordinated national coroner's law and contempt for accurate and detailed death records. Worse still, no valid tenable death certificate has ever been issued. In other words, no attempt has been made to determine the cause of death of four of the nation's former leaders. Only hurried national burials were accorded two (50%) of them while the other two (50%), who died in the coup and revenge coup of 1966, were completely neglected, and not even given a decent national burial. The facts identified above will serve as

  3. Escaping the tolerance trap

    International Nuclear Information System (INIS)

    Hammoudeh, S.; Madan, V.


    In order to examine the implications of the weakening of OPEC's responsiveness in adjusting its production levels, this paper explicitly incorporates rigidity in the quantity adjustment mechanism, thereby extending previous research which assumed smooth quantity adjustments. The rigidity is manifested in a tolerance range for the discrepancy between the declared target price and that of the market. This environment gives rise to a 'tolerance trap' which impedes the convergence process and inevitably brings the market to a standstill before its reaches the targeted price and revenue objectives. OPEC's reaction to the standstill has important implications for the achievement of the target-based equilibrium and for the potential collapse of the market price. This paper examines OPEC's policy options in the tolerance trap and reveals that the optional policy in order to break this impasse and move closer to the equilibrium point is gradually to reduce output and not to flood the market. (Author)

  4. Trapped Ion Qubits

    Energy Technology Data Exchange (ETDEWEB)

    Maunz, Peter Lukas Wilhelm


    Qubits can be encoded in clock states of trapped ions. These states are well isolated from the environment resulting in long coherence times [1] while enabling efficient high-fidelity qubit interactions mediated by the Coulomb coupled motion of the ions in the trap. Quantum states can be prepared with high fidelity and measured efficiently using fluorescence detection. State preparation and detection with 99.93% fidelity have been realized in multiple systems [1,2]. Single qubit gates have been demonstrated below rigorous fault-tolerance thresholds [1,3]. Two qubit gates have been realized with more than 99.9% fidelity [4,5]. Quantum algorithms have been demonstrated on systems of 5 to 15 qubits [6–8].

  5. Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy (United States)


    report. Inventions, patent applications, and/or licenses Nothing to report. Others Nothing to report. 7. Participants & Other... Brand LJ et al: Androgen receptor splice variants mediate enzalutamide resistance in castration-resistant prostate cancer cell lines. Cancer Res

  6. Minor class splicing shapes the zebrafish transcriptome during development

    DEFF Research Database (Denmark)

    Markmiller, Sebastian; Cloonan, Nicole; Lardelli, Rea M


    Minor class or U12-type splicing is a highly conserved process required to remove a minute fraction of introns from human pre-mRNAs. Defects in this splicing pathway have recently been linked to human disease, including a severe developmental disorder encompassing brain and skeletal abnormalities...... known as Taybi-Linder syndrome or microcephalic osteodysplastic primordial dwarfism 1, and a hereditary intestinal polyposis condition, Peutz-Jeghers syndrome. Although a key mechanism for regulating gene expression, the impact of impaired U12-type splicing on the transcriptome is unknown. Here, we...... as the U11/U12 di-snRNP 65-kDa protein, a unique component of the U12-type spliceosome. The biochemical impact of the mutation in clbn is the formation of aberrant U11- and U12-containing small nuclear ribonucleoproteins that impair the efficiency of U12-type splicing. Using RNA sequencing and microarrays...

  7. Ethical leader behavior and leader effectiveness: the role of prototypicality and trust


    Kalshoven, K.; den Hartog, D.N.


    The study examines factors that mediate the impact of ethical leader behavior on leader effectiveness. Little is known about how ethical leadership impacts leader effectiveness. We hypothesized that prototypicality and trust sequentially mediate the relationship between ethical leader behavior and perceived leader effectiveness. The group prototype forms an ideal representation of the group’s identity, prescribing appropriate attitudes and behaviors. Ethical leaders are role models and thus a...

  8. Leader self-sacrifice and leadership effectiveness: The moderating role of leader prototypicality


    van Knippenberg, B.M.; van Knippenberg, D.


    Self-sacrificing behavior of the leader and the extent to which the leader is representative of the group (i.e., group prototypical) are proposed to interact to influence leadership effectiveness. The authors expected self-sacrificing leaders to be considered more effective and to be able to push subordinates to a higher performance level than non-self-sacrificing leaders, and these effects were expected to be more pronounced for less prototypical leaders than for more prototypical leaders. T...

  9. Sediment Trapping in Estuaries (United States)

    Burchard, Hans; Schuttelaars, Henk M.; Ralston, David K.


    Estuarine turbidity maxima (ETMs) are generated by a large suite of hydrodynamic and sediment dynamic processes, leading to longitudinal convergence of cross-sectionally integrated and tidally averaged transport of cohesive and noncohesive suspended particulate matter (SPM). The relative importance of these processes for SPM trapping varies substantially among estuaries depending on topography, fluvial and tidal forcing, and SPM composition. The high-frequency dynamics of ETMs are constrained by interactions with the low-frequency dynamics of the bottom pool of easily erodible sediments. Here, we use a transport decomposition to present processes that lead to convergent SPM transport, and review trapping mechanisms that lead to ETMs at the landward limit of the salt intrusion, in the freshwater zone, at topographic transitions, and by lateral processes within the cross section. We use model simulations of example estuaries to demonstrate the complex concurrence of ETM formation mechanisms. We also discuss how changes in SPM trapping mechanisms, often caused by direct human interference, can lead to the generation of hyperturbid estuaries.

  10. Width of gene expression profile drives alternative splicing.

    Directory of Open Access Journals (Sweden)

    Daniel Wegmann

    Full Text Available Alternative splicing generates an enormous amount of functional and proteomic diversity in metazoan organisms. This process is probably central to the macromolecular and cellular complexity of higher eukaryotes. While most studies have focused on the molecular mechanism triggering and controlling alternative splicing, as well as on its incidence in different species, its maintenance and evolution within populations has been little investigated. Here, we propose to address these questions by comparing the structural characteristics as well as the functional and transcriptional profiles of genes with monomorphic or polymorphic splicing, referred to as MS and PS genes, respectively. We find that MS and PS genes differ particularly in the number of tissues and cell types where they are expressed.We find a striking deficit of PS genes on the sex chromosomes, particularly on the Y chromosome where it is shown not to be due to the observed lower breadth of expression of genes on that chromosome. The development of a simple model of evolution of cis-regulated alternative splicing leads to predictions in agreement with these observations. It further predicts the conditions for the emergence and the maintenance of cis-regulated alternative splicing, which are both favored by the tissue specific expression of splicing variants. We finally propose that the width of the gene expression profile is an essential factor for the acquisition of new transcript isoforms that could later be maintained by a new form of balancing selection.

  11. Splice site mutations in the ATP7A gene.

    Directory of Open Access Journals (Sweden)

    Tina Skjørringe

    Full Text Available Menkes disease (MD is caused by mutations in the ATP7A gene. We describe 33 novel splice site mutations detected in patients with MD or the milder phenotypic form, Occipital Horn Syndrome. We review these 33 mutations together with 28 previously published splice site mutations. We investigate 12 mutations for their effect on the mRNA transcript in vivo. Transcriptional data from another 16 mutations were collected from the literature. The theoretical consequences of splice site mutations, predicted with the bioinformatics tool Human Splice Finder, were investigated and evaluated in relation to in vivo results. Ninety-six percent of the mutations identified in 45 patients with classical MD were predicted to have a significant effect on splicing, which concurs with the absence of any detectable wild-type transcript in all 19 patients investigated in vivo. Sixty-seven percent of the mutations identified in 12 patients with milder phenotypes were predicted to have no significant effect on splicing, which concurs with the presence of wild-type transcript in 7 out of 9 patients investigated in vivo. Both the in silico predictions and the in vivo results support the hypothesis previously suggested by us and others, that the presence of some wild-type transcript is correlated to a milder phenotype.

  12. Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction

    Directory of Open Access Journals (Sweden)

    Marcin Szczot


    Full Text Available Summary: Piezo2 is a mechanically activated ion channel required for touch discrimination, vibration detection, and proprioception. Here, we discovered that Piezo2 is extensively spliced, producing different Piezo2 isoforms with distinct properties. Sensory neurons from both mice and humans express a large repertoire of Piezo2 variants, whereas non-neuronal tissues express predominantly a single isoform. Notably, even within sensory ganglia, we demonstrate the splicing of Piezo2 to be cell type specific. Biophysical characterization revealed substantial differences in ion permeability, sensitivity to calcium modulation, and inactivation kinetics among Piezo2 splice variants. Together, our results describe, at the molecular level, a potential mechanism by which transduction is tuned, permitting the detection of a variety of mechanosensory stimuli. : Szczot et al. find that the mechanoreceptor Piezo2 is extensively alternatively spliced, generating multiple distinct isoforms. Their findings indicate that these splice products have specific tissue and cell type expression patterns and exhibit differences in receptor properties. Keywords: Piezo, touch, sensation, ion-channel, splicing

  13. Abnormalities in Alternative Splicing of Apoptotic Genes and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Zodwa Dlamini


    Full Text Available Apoptosis is required for normal heart development in the embryo, but has also been shown to be an important factor in the occurrence of heart disease. Alternative splicing of apoptotic genes is currently emerging as a diagnostic and therapeutic target for heart disease. This review addresses the involvement of abnormalities in alternative splicing of apoptotic genes in cardiac disorders including cardiomyopathy, myocardial ischemia and heart failure. Many pro-apoptotic members of the Bcl-2 family have alternatively spliced isoforms that lack important active domains. These isoforms can play a negative regulatory role by binding to and inhibiting the pro-apoptotic forms. Alternative splicing is observed to be increased in various cardiovascular diseases with the level of alternate transcripts increasing elevated in diseased hearts compared to healthy subjects. In many cases these isoforms appear to be the underlying cause of the disease, while in others they may be induced in response to cardiovascular pathologies. Regardless of this, the detection of alternate splicing events in the heart can serve as useful diagnostic or prognostic tools, while those splicing events that seem to play a causative role in cardiovascular disease make attractive future drug targets.

  14. Strategic Communications for School Leaders (United States)

    Gunther, Vicki; McGowan, James; Donegan, Kate


    Gunther, McGowan and Donegan draw on their own experiences and those of others in the field, to explain the importance of communication in school leadership. In focusing on the communication process--why it's critical for schools, and how it can be executed well--they make the case that communication must be a primary emphasis for leaders, not an…

  15. LEADER-tegevusest / Ene Sarapuu

    Index Scriptorium Estoniae

    Sarapuu, Ene


    Läänemaa LEADER-tegevusgrupi eesmärk on maakonna kui terviku ühtne areng, et kogu Läänemaa oleks vajalike teenustega kaetud ning ettevõtjad julgeks ning suudaks uute teenuste ja toodetega turule tulla

  16. The psychology of ethical leaders

    NARCIS (Netherlands)

    N. Hoogervorst (Niek)


    textabstractThe collateral damage to companies caused by unethical behaviour can be enormous, especially when it is perceived to be systemic within an organisation. We look to leaders to set an example. So how can they be encouraged to set aside selfinterest and provide an ethical role model for

  17. Competition policy and market leaders

    Czech Academy of Sciences Publication Activity Database

    Maci, Ilir; Žigić, K.

    -, č. 375 (2008), s. 1-29 ISSN 1211-3298 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:AV0Z70850503 Keywords : competition policy * market leaders * innovation Subject RIV: AH - Economics

  18. Competition policy and market leaders

    Czech Academy of Sciences Publication Activity Database

    Maci, I.; Žigić, Krešimir

    -, č. 375 (2008), s. 1-29 ISSN 1211-3298 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:MSM0021620846 Keywords : competition policy * market leaders * innovation Subject RIV: AH - Economics

  19. Understanding the Supplemental Instruction Leader (United States)

    James, Adrian; Moore, Lori


    This article explored the learning styles and leadership styles of Supplemental Instruction (SI) leaders at Texas A&M University, and the impact of those preferences on recurring attendance to their sessions. The Learning Style Inventory, the Multifactor Leadership Questionnaire, and a demographic instrument were administered to SI leaders…

  20. Do leaders affect ethical conduct?

    NARCIS (Netherlands)

    d'Adda, Giovanna; Darai, Donja; Pavanini, Nicola; Weber, Roberto A.


    We study whether leaders influence the unethical conduct of followers. To avoid selection issues present in natural environments, we use an experiment in which we create simple laboratory firms and assign leadership roles at random. In our first experiment, firms engage in competition and unethical

  1. The failure-tolerant leader. (United States)

    Farson, Richard; Keyes, Ralph


    "The fastest way to succeed," IBM's Thomas Watson, Sr., once said, "is to double your failure rate." In recent years, more and more executives have embraced Watson's point of view, coming to understand what innovators have always known: Failure is a prerequisite to invention. But while companies may grasp the value of making mistakes at the level of corporate practices, they have a harder time accepting the idea at the personal level. People are afraid to fail, and corporate culture reinforces that fear. In this article, psychologist and former Harvard Business School professor Richard Farson and coauthor Ralph Keyes discuss how companies can reduce the fear of miscues. What's crucial is the presence of failure-tolerant leaders--executives who, through their words and actions, help employees overcome their anxieties about making mistakes and, in the process, create a culture of intelligent risk-taking that leads to sustained innovation. Such leaders don't just accept productive failure, they promote it. Drawing from their research in business, politics, sports, and science, the authors identify common practices among failure-tolerant leaders. These leaders break down the social and bureaucratic barriers that separate them from their followers. They engage at a personal level with the people they lead. They avoid giving either praise or criticism, preferring to take a nonjudgmental, analytical posture as they interact with staff. They openly admit their own mistakes rather than trying to cover them up or shifting the blame. And they try to root out the destructive competitiveness built into most organizations. Above all else, failure-tolerant leaders push people to see beyond traditional definitions of success and failure. They know that as long as a person views failure as the opposite of success, rather than its complement, he or she will never be able to take the risks necessary for innovation.

  2. Morpholino antisense oligo inhibits trans-splicing of pre-inositol 1,4,5-trisphosphate receptor mRNA of Trypanosoma cruzi and suppresses parasite growth and infectivity. (United States)

    Hashimoto, Muneaki; Nara, Takeshi; Mita, Toshihiro; Mikoshiba, Katsuhiko


    Morpholino antisense oligos (MAOs) are used to investigate physiological gene function by inhibiting gene translation or construction of specific alternative splicing variants by blocking cis-splicing. MAOs are attractive drug candidates for viral- and bacterial-infectious disease therapy because of properties such as in vivo stability and specificity to target genes. Recently, we showed that phosphorothioate antisense oligos against Trypanosoma cruzi inositol 1,4,5-trisphosphate receptor (TcIP(3)R) mRNA inhibit the parasite host cell infection. In the present study, we identified the spliced leader (SL) acceptor of pre-TcIP(3)R mRNA and synthesized MAO, which inhibited trans-splicing of the transcript (MAO-1). MAO-1 was found to inhibit the addition of SL-RNA to pre-TcIP(3)R mRNA by real-time RT-PCR analysis. Treatment of the parasites with MAO-1 significantly impaired the growth and infectivity into host cells. These results indicate that MAO-1 is a potential novel drug for Chagas disease and that MAOs inhibiting trans-splicing can be used to investigate the physiology of trypanosomal genes leading to the development of novel drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Novel female-specific trans-spliced and alternative splice forms of dsx in the silkworm Bombyx mori. (United States)

    Duan, Jianping; Xu, Hanfu; Wang, Feng; Ma, Sanyuan; Zha, Xingfu; Guo, Huizhen; Zhao, Ping; Xia, Qingyou


    The Bombyx mori doublesex gene (Bmdsx) plays an important role in somatic sexual development. Its pre-mRNA splices in a sex-specific manner to generate two female-specific and one male-specific splice forms. The present study investigated six novel dsx variants generated by trans-splicing between female dsx transcripts and two additional novel genes, dsr1 and dsr2. Expression analysis indicated that Bmdsx-dsr1 represented splicing noise, whereas dsr2, which trans-spliced with dsx to generate five variants, regulated the expression of the female-specific B. mori dsx transcript Bmdsx(F)s. We unexpectedly found a novel exon 2n insertion during Bmdsx transcription, which did not influence the validity of the novel protein, BmDSX(F3). Ectopic expression of BmDSX(F3) repressed the pheromone-binding protein gene and the testis-specific gene A2 in males, and activated of the storage protein 1 gene. Our findings suggest that trans-splicing is a novel regulatory function of Bmdsx, which participates in female sexual development by regulating the expression of three BmDSX(F) proteins. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. The Nurse Leader Role in Crisis Management. (United States)

    Edmonson, Cole; Sumagaysay, Dio; Cueman, Marie; Chappell, Stacey


    Leaders from the American Organization of Nurse Executives describe the dynamic state of today's healthcare system related to crisis management. Adaptive leadership, driven by strong values and morality, can guide leaders and organizations through the most difficult times.

  5. Kansas nurse leader residency programme: advancing leader knowledge and skills. (United States)

    Shen, Qiuhua; Peltzer, Jill; Teel, Cynthia; Pierce, Janet


    To evaluate the effectiveness of the Kansas Nurse Leader Residency (KNLR) programme in improving nurses' leadership knowledge and skills and its acceptability, feasibility and fidelity. The Future of Nursing Report (Institute of Medicine, 2011) calls for nurses to lead change and advance health. The 6-month KNLR programme was developed by the Kansas Action Coalition to support nurses' leadership development. Nurses (n = 36) from four nursing specialties (acute care, long-term care, public health and school health) participated in the programme. The adapted Leader Knowledge and Skill Inventory was used to assess leadership knowledge and skills. Programme acceptability, feasibility and implementation fidelity also were evaluated. The programme completion rate was 67.7% (n = 24). Programme completers had significantly improved self-assessed and mentor-assessed leadership knowledge and skills (p programme gains were maintained 3 months after programme completion. The KNLR programme effectively improved leadership knowledge and skills and was positively evaluated by participants. The implementation of the KNLR programme using a hybrid format of in-person sessions and online modules was feasible across four specialty areas in both rural and urban regions. The next steps include the development of an advanced programme. Residency programmes for new nurse leaders are critical for successful transition into management positions. © 2017 John Wiley & Sons Ltd.

  6. The Honey Trap

    DEFF Research Database (Denmark)

    Wagner, Michael

    Michael F. Wagner: The Honey Trap –The democratization of leisure through automobilism The automobile has achieved a central position in modern everyday life as an essential artefact to mobility. This raises the question how automobiles have been mediated for mass consumption? The central thesis...... demonstrates the manner in which automobilism in Denmark was invented, constructed, represented, and appropriated as a leisure culture after 1900 through a mediation and consumption junction that was initiated and promoted by FDM. This is basically the story of unlimited access to Sunday driving or the daytrip...

  7. Atom trap trace analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Z.-T.; Bailey, K.; Chen, C.-Y.; Du, X.; Li, Y.-M.; O' Connor, T. P.; Young, L.


    A new method of ultrasensitive trace-isotope analysis has been developed based upon the technique of laser manipulation of neutral atoms. It has been used to count individual {sup 85}Kr and {sup 81}Kr atoms present in a natural krypton sample with isotopic abundances in the range of 10{sup {minus}11} and 10{sup {minus}13}, respectively. The atom counts are free of contamination from other isotopes, elements,or molecules. The method is applicable to other trace-isotopes that can be efficiently captured with a magneto-optical trap, and has a broad range of potential applications.

  8. Recruiting leaders: an analysis of leadership advertisements

    NARCIS (Netherlands)

    den Hartog, D.N.; Caley, A.; Dewe, P.


    Recruiting the right leaders is an important challenge for organisations. How do organisations find these leaders? This article looks at the recruitment of leaders through advertisements. We address to what extent the 'vocabulary of leadership' originating in influential leadership theories is

  9. A Phenomenology of Outdoor Education Leader Experiences (United States)

    Field, Stephanie C.; Lauzon, Lara L.; Meldrum, John T.


    Limited qualitative research exists on the experiences of outdoor education leaders. The purpose of this phenomenological study was to explore the job-related experiences of outdoor education leaders within and outside the workplace. Five participants who had experience as outdoor education leaders completed in-depth, one-on-one interviews about…

  10. Method of predicting Splice Sites based on signal interactions

    Directory of Open Access Journals (Sweden)

    Deogun Jitender S


    Full Text Available Abstract Background Predicting and proper ranking of canonical splice sites (SSs is a challenging problem in bioinformatics and machine learning communities. Any progress in SSs recognition will lead to better understanding of splicing mechanism. We introduce several new approaches of combining a priori knowledge for improved SS detection. First, we design our new Bayesian SS sensor based on oligonucleotide counting. To further enhance prediction quality, we applied our new de novo motif detection tool MHMMotif to intronic ends and exons. We combine elements found with sensor information using Naive Bayesian Network, as implemented in our new tool SpliceScan. Results According to our tests, the Bayesian sensor outperforms the contemporary Maximum Entropy sensor for 5' SS detection. We report a number of putative Exonic (ESE and Intronic (ISE Splicing Enhancers found by MHMMotif tool. T-test statistics on mouse/rat intronic alignments indicates, that detected elements are on average more conserved as compared to other oligos, which supports our assumption of their functional importance. The tool has been shown to outperform the SpliceView, GeneSplicer, NNSplice, Genio and NetUTR tools for the test set of human genes. SpliceScan outperforms all contemporary ab initio gene structural prediction tools on the set of 5' UTR gene fragments. Conclusion Designed methods have many attractive properties, compared to existing approaches. Bayesian sensor, MHMMotif program and SpliceScan tools are freely available on our web site. Reviewers This article was reviewed by Manyuan Long, Arcady Mushegian and Mikhail Gelfand.

  11. Magnetic traps with a spherical separatrix: Tornado traps

    International Nuclear Information System (INIS)

    Peregood, B.P.; Lehnert, B.


    A review is given on the features of magnetic traps with a spherical separatrix, with special emphasis on Tornado spiral coil configurations. The confinement and heating of static plasms in Tornado traps is treated, including the topology of the magnetic field structure, the magneto-mechanical properties of the magnetic coil system, as well as the particle orbits and plasma behaviour in these traps. In addition, the mode of rotating plasma operation by crossed electric and magnetic fields is described. The results of experiments on static and rotating plasmas are summarized, and conclusions are drawn about future possibilities of Tornado traps in the creation and containment of hot plasmas. (orig.)

  12. Characteristics of trapped electrons and electron traps in single crystals

    International Nuclear Information System (INIS)

    Budzinski, E.E.; Potter, W.R.; Potienko, G.; Box, H.C.


    Two additional carbohydrates are reported whose crystal structures trap electrons intermolecularly in single crystals x irradiated at low temperature, namely sucrose and rhamnose. Five carbohydrate and polyhydroxy compounds are now known which exhibit this phenomenon. The following characteristics of the phenomenon were investigated: (1) the hyperfine couplings of the electron with protons of the polarized hydroxy groups forming the trap; (2) the distances between these protons and the trapped electron; (3) the spin density of the electron at the protons and (4) the relative stabilities of the electron trapped in various crystal structures

  13. Strategic Communication for Tactical Leaders (United States)


    made by many different instruments into a single, harmonious work of music . The conductor of the orchestra represents senior strategic communication...defining a tactical- level leader challenging. However, FM 3-0 eventually gives some further resolution and states that tactics “are typically ...visitors will be compared against other websites of its genre . For example, to determine if is a well-established and mainstream video


    Directory of Open Access Journals (Sweden)

    A. Vacar


    Full Text Available This article is a small part of a long empirical and practical research and it began from the necessity of models to be followed in organizations and the way they can generate that expected behavior from others. Nowadays, projects seem to be the modern way of doing things in organizations because of their advantages. The article tries to present common issues between leaders and projects, both of them being as determinant factors for organizational success.

  15. From One Leader to Another (United States)


    regulation. Commanders cannot tolerate financial irresponsibility, neglect, dishonesty or evasiveness . If a Soldier is not trying to resolve injuries to diarrhea, and from pneumonia, encephalitis to viruses . The medical readiness of these troops could have been higher if leaders played...understand just how false this is, we have to recognize that everyone has a “breaking point.” No one is immune to the lingering effects of the struggles

  16. Analysis of a splice array experiment elucidates roles of chromatin elongation factor Spt4-5 in splicing.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Xiao


    Full Text Available Splicing is an important process for regulation of gene expression in eukaryotes, and it has important functional links to other steps of gene expression. Two examples of these linkages include Ceg1, a component of the mRNA capping enzyme, and the chromatin elongation factors Spt4-5, both of which have recently been shown to play a role in the normal splicing of several genes in the yeast Saccharomyces cerevisiae. Using a genomic approach to characterize the roles of Spt4-5 in splicing, we used splicing-sensitive DNA microarrays to identify specific sets of genes that are mis-spliced in ceg1, spt4, and spt5 mutants. In the context of a complex, nested, experimental design featuring 22 dye-swap array hybridizations, comprising both biological and technical replicates, we applied five appropriate statistical models for assessing differential expression between wild-type and the mutants. To refine selection of differential expression genes, we then used a robust model-synthesizing approach, Differential Expression via Distance Synthesis, to integrate all five models. The resultant list of differentially expressed genes was then further analyzed with regard to select attributes: we found that highly transcribed genes with long introns were most sensitive to spt mutations. QPCR confirmation of differential expression was established for the limited number of genes evaluated. In this paper, we showcase splicing array technology, as well as powerful, yet general, statistical methodology for assessing differential expression, in the context of a real, complex experimental design. Our results suggest that the Spt4-Spt5 complex may help coordinate splicing with transcription under conditions that present kinetic challenges to spliceosome assembly or function.

  17. Leader Affect and Leadership Effectiveness: How leader affective displays influence follower outcomes


    Visser, Victoria


    textabstractThe aim of this dissertation is to uncover the relationship between leader affective displays and leadership effectiveness. Five empirical studies were conducted to test the influence of several leader affective displays on different follower outcomes that indicate leadership effectiveness. The results showed that leader happy displays enhance followers’ creative performance, whereas leader sad displays enhance followers’ analytical performance. In addition, a leader displaying ha...

  18. Facing an incompetent leader: The effects of a nonexpert leader on subordinates' perception and behaviour


    Darioly, Annick; Schmid Mast, Marianne


    We investigated the effects of a leader's task-incompetence on how subordinates perceive and interact with their leader. In Study 1, 80 participants in a subordinate role interacted via e-mail and in Study 2, 80 participants interacted face-to-face with either a competent or an incompetent leader on a problem-solving task. Participants' dominance behaviour, how much they resisted the leader's influence, their perception of the leader, and their task involvement were assessed. As predicted, su...

  19. Two new splice variants in porcine PPARGC1A

    Directory of Open Access Journals (Sweden)

    Peelman Luc J


    Full Text Available Abstract Background Peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A is a coactivator with a vital and central role in fat and energy metabolism. It is considered to be a candidate gene for meat quality in pigs and is involved in the development of obesity and diabetes in humans. How its many functions are regulated, is however still largely unclear. Therefore a transcription profile of PPARGC1A in 32 tissues and 4 embryonic developmental stages in the pig was constructed by screening its cDNA for possible splice variants with exon-spanning primers. Findings This led to the discovery of 2 new splice variants in the pig, which were subsequently also detected in human tissues. In these variants, exon 8 was either completely or partly (the last 66 bp were conserved spliced out, potentially coding for a much shorter protein of respectively 337 and 359 amino acids (aa, of which the first 291 aa would be the same compared to the complete protein (796 aa. Conclusion Considering the functional domains of the PPARGC1A protein, it is very likely these splice variants considerably affect the function of the protein and alternative splicing could be one of the mechanisms by which the diverse functions of PPARGC1A are regulated.

  20. The impact of previous leaders on the evaluation of new leaders: an alternative to prototype matching. (United States)

    Ritter, Barbara A; Lord, Robert G


    In 2 studies, this research demonstrated the existence of leader transference, a cognitive process whereby mental representations of previous leaders are activated and used for evaluation when new, similar leaders are encountered. The 1st study demonstrated that exposure to a new leader who was similar to a past leader led to erroneous generalization of leader characteristics and associated underlying attributions. The 2nd study showed that expectations of just treatment and abuse were also subject to transfer from old to new, similar leaders, although positive and negative affective responses were not. Results suggested that individuals exposed to a leader who was not reminiscent of an old leader were more likely to use a general leader prototype to form leader expectations, whereas individuals exposed to a leader who was similar to an old leader activated a significant other mental representation for use in making judgments. These results have implications for individual- and relational-level processes as characterized by implicit leadership theory and leader-member exchange theory as well as macro theories of leader succession and organizational culture change. (c) 2007 APA

  1. Sample Processor for Life on Icy Worlds (SPLIce): Design and Test Results (United States)

    Chinn, Tori N.; Lee, Anthony K.; Boone, Travis D.; Tan, Ming X.; Chin, Matthew M.; McCutcheon, Griffin C.; Horne, Mera F.; Padgen, Michael R.; Blaich, Justin T.; Forgione, Joshua B.; hide


    -olefin polymer, supports all fluidic components (Figure 1) and integrated microchannels (125 x 250 m). Fluid is pumped by a stepper-motor-driven pump (Lee Co.). The functionality of the integrated MEMS pressure sensor (Honeywell) and passive check valves (Figure 2) were tested in conjunction with our newly designed integral bubble traps (Figure 3) and hydrophobic membrane-based concentrator (Figure 4). The concentrator (initially tested as a standalone component) demonstrated 5-fold vacuum-evaporative concentration. Polyethylene fused bead beds (PEFBBs; 50 porosity) store drylyophilized buffers, calibrants, and fluorescent dyes, and also promote mixing of sample with calibrant, dye, or H2O. Software-controlled automated tests demonstrated successful 1) fluid delivery to each component 2) valve and pump synchronization 3) sample aliquot delivery to instrument interface ports, and 4) rehydration of vacuum-dried fluorescent dye. In Figure 5, fluorescein on PEFBBs was rehydrated for 15 min using a pump-delivered water aliquot; it is displaced as H2O enters the bottom of the channel and pushes the dye into a check valve. Ultimately, SPLIce will fluorescently label amino acids in the sample for microchip-based electrophoretic (MCE) chiral separation and detection to seek and quantify key organic bio-signatures [5]; it will also deliver sample to a microfluidic version of WCL (mWCL) to measure soluble ions and redox-active species.

  2. Segmented trapped vortex cavity (United States)

    Grammel, Jr., Leonard Paul (Inventor); Pennekamp, David Lance (Inventor); Winslow, Jr., Ralph Henry (Inventor)


    An annular trapped vortex cavity assembly segment comprising includes a cavity forward wall, a cavity aft wall, and a cavity radially outer wall there between defining a cavity segment therein. A cavity opening extends between the forward and aft walls at a radially inner end of the assembly segment. Radially spaced apart pluralities of air injection first and second holes extend through the forward and aft walls respectively. The segment may include first and second expansion joint features at distal first and second ends respectively of the segment. The segment may include a forward subcomponent including the cavity forward wall attached to an aft subcomponent including the cavity aft wall. The forward and aft subcomponents include forward and aft portions of the cavity radially outer wall respectively. A ring of the segments may be circumferentially disposed about an axis to form an annular segmented vortex cavity assembly.

  3. A human haploid gene trap collection to study lncRNAs with unusual RNA biology. (United States)

    Kornienko, Aleksandra E; Vlatkovic, Irena; Neesen, Jürgen; Barlow, Denise P; Pauler, Florian M


    Many thousand long non-coding (lnc) RNAs are mapped in the human genome. Time consuming studies using reverse genetic approaches by post-transcriptional knock-down or genetic modification of the locus demonstrated diverse biological functions for a few of these transcripts. The Human Gene Trap Mutant Collection in haploid KBM7 cells is a ready-to-use tool for studying protein-coding gene function. As lncRNAs show remarkable differences in RNA biology compared to protein-coding genes, it is unclear if this gene trap collection is useful for functional analysis of lncRNAs. Here we use the uncharacterized LOC100288798 lncRNA as a model to answer this question. Using public RNA-seq data we show that LOC100288798 is ubiquitously expressed, but inefficiently spliced. The minor spliced LOC100288798 isoforms are exported to the cytoplasm, whereas the major unspliced isoform is nuclear localized. This shows that LOC100288798 RNA biology differs markedly from typical mRNAs. De novo assembly from RNA-seq data suggests that LOC100288798 extends 289kb beyond its annotated 3' end and overlaps the downstream SLC38A4 gene. Three cell lines with independent gene trap insertions in LOC100288798 were available from the KBM7 gene trap collection. RT-qPCR and RNA-seq confirmed successful lncRNA truncation and its extended length. Expression analysis from RNA-seq data shows significant deregulation of 41 protein-coding genes upon LOC100288798 truncation. Our data shows that gene trap collections in human haploid cell lines are useful tools to study lncRNAs, and identifies the previously uncharacterized LOC100288798 as a potential gene regulator.

  4. Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome

    Directory of Open Access Journals (Sweden)

    María E. Teresa-Rodrigo


    Full Text Available Cornelia de Lange syndrome (CdLS is a congenital developmental disorder characterized by distinctive craniofacial features, growth retardation, cognitive impairment, limb defects, hirsutism, and multisystem involvement. Mutations in five genes encoding structural components (SMC1A, SMC3, RAD21 or functionally associated factors (NIPBL, HDAC8 of the cohesin complex have been found in patients with CdLS. In about 60% of the patients, mutations in NIPBL could be identified. Interestingly, 17% of them are predicted to change normal splicing, however, detailed molecular investigations are often missing. Here, we report the first systematic study of the physiological splicing of the NIPBL gene, that would reveal the identification of four new splicing isoforms ΔE10, ΔE12, ΔE33,34, and B’. Furthermore, we have investigated nine mutations affecting splice-sites in the NIPBL gene identified in twelve CdLS patients. All mutations have been examined on the DNA and RNA level, as well as by in silico analyses. Although patients with mutations affecting NIPBL splicing show a broad clinical variability, the more severe phenotypes seem to be associated with aberrant transcripts resulting in a shift of the reading frame.

  5. Understanding pre-mRNA splicing through crystallography. (United States)

    Espinosa, Sara; Zhang, Lingdi; Li, Xueni; Zhao, Rui


    Crystallography is a powerful tool to determine the atomic structures of proteins and RNAs. X-ray crystallography has been used to determine the structure of many splicing related proteins and RNAs, making major contributions to our understanding of the molecular mechanism and regulation of pre-mRNA splicing. Compared to other structural methods, crystallography has its own advantage in the high-resolution structural information it can provide and the unique biological questions it can answer. In addition, two new crystallographic methods - the serial femtosecond crystallography and 3D electron crystallography - were developed to overcome some of the limitations of traditional X-ray crystallography and broaden the range of biological problems that crystallography can solve. This review discusses the theoretical basis, instrument requirements, troubleshooting, and exciting potential of these crystallographic methods to further our understanding of pre-mRNA splicing, a critical event in gene expression of all eukaryotes. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Stabilized cyclopropane analogs of the splicing inhibitor FD-895. (United States)

    Villa, Reymundo; Kashyap, Manoj Kumar; Kumar, Deepak; Kipps, Thomas J; Castro, Januario E; La Clair, James J; Burkart, Michael D


    Targeting the spliceosome with small molecule inhibitors provides a new avenue to target cancer by intercepting alternate splicing pathways. Although our understanding of alternate mRNA splicing remains poorly understood, it provides an escape pathway for many cancers resistant to current therapeutics. These findings have encouraged recent academic and industrial efforts to develop natural product spliceosome inhibitors, including FD-895 (1a), pladienolide B (1b), and pladienolide D (1c), into next-generation anticancer drugs. The present study describes the application of semisynthesis and total synthesis to reveal key structure-activity relationships for the spliceosome inhibition by 1a. This information is applied to deliver new analogs with improved stability and potent activity at inhibiting splicing in patient derived cell lines.

  7. Body Temperature Cycles Control Rhythmic Alternative Splicing in Mammals. (United States)

    Preußner, Marco; Goldammer, Gesine; Neumann, Alexander; Haltenhof, Tom; Rautenstrauch, Pia; Müller-McNicoll, Michaela; Heyd, Florian


    The core body temperature of all mammals oscillates with the time of the day. However, direct molecular consequences of small, physiological changes in body temperature remain largely elusive. Here we show that body temperature cycles drive rhythmic SR protein phosphorylation to control an alternative splicing (AS) program. A temperature change of 1°C is sufficient to induce a concerted splicing switch in a large group of functionally related genes, rendering this splicing-based thermometer much more sensitive than previously described temperature-sensing mechanisms. AS of two exons in the 5' UTR of the TATA-box binding protein (Tbp) highlights the general impact of this mechanism, as it results in rhythmic TBP protein levels with implications for global gene expression in vivo. Together our data establish body temperature-driven AS as a core clock-independent oscillator in mammalian peripheral clocks. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Cloning, expression and alternative splicing of the novel isoform of hTCP11 gene

    DEFF Research Database (Denmark)

    Ma, Yong-xin; Zhang, Si-zhong; Wu, Qia-qing


    To identify a novel isoform of hTCP11 gene and investigate its expression and alternative splicing.......To identify a novel isoform of hTCP11 gene and investigate its expression and alternative splicing....

  9. Minor class splicing shapes the zebrafish transcriptome during development. (United States)

    Markmiller, Sebastian; Cloonan, Nicole; Lardelli, Rea M; Doggett, Karen; Keightley, Maria-Cristina; Boglev, Yeliz; Trotter, Andrew J; Ng, Annie Y; Wilkins, Simon J; Verkade, Heather; Ober, Elke A; Field, Holly A; Grimmond, Sean M; Lieschke, Graham J; Stainier, Didier Y R; Heath, Joan K


    Minor class or U12-type splicing is a highly conserved process required to remove a minute fraction of introns from human pre-mRNAs. Defects in this splicing pathway have recently been linked to human disease, including a severe developmental disorder encompassing brain and skeletal abnormalities known as Taybi-Linder syndrome or microcephalic osteodysplastic primordial dwarfism 1, and a hereditary intestinal polyposis condition, Peutz-Jeghers syndrome. Although a key mechanism for regulating gene expression, the impact of impaired U12-type splicing on the transcriptome is unknown. Here, we describe a unique zebrafish mutant, caliban (clbn), with arrested development of the digestive organs caused by an ethylnitrosourea-induced recessive lethal point mutation in the rnpc3 [RNA-binding region (RNP1, RRM) containing 3] gene. rnpc3 encodes the zebrafish ortholog of human RNPC3, also known as the U11/U12 di-snRNP 65-kDa protein, a unique component of the U12-type spliceosome. The biochemical impact of the mutation in clbn is the formation of aberrant U11- and U12-containing small nuclear ribonucleoproteins that impair the efficiency of U12-type splicing. Using RNA sequencing and microarrays, we show that multiple genes involved in various steps of mRNA processing, including transcription, splicing, and nuclear export are disrupted in clbn, either through intron retention or differential gene expression. Thus, clbn provides a useful and specific model of aberrant U12-type splicing in vivo. Analysis of its transcriptome reveals efficient mRNA processing as a critical process for the growth and proliferation of cells during vertebrate development.

  10. Analysis for Behavior of Reinforcement Lap Splices in Deep Beams

    Directory of Open Access Journals (Sweden)

    Ammar Yaser Ali


    Full Text Available The present study includes an experimental and theoretical investigation of reinforced concrete deep beams containing tensile reinforcement lap splices at constant moment zone under static load. The study included two stages: in the first one, an experimental work included testing of eight simply supported RC deep beams having a total length (L = 2000 mm, overall depth (h= 600 mm and width (b = 150 mm. The tested specimens were divided into three groups to study the effect of main variables: lap length, location of splice, internal confinement (stirrups and external confinement (strengthening by CFRP laminates. The experimental results showed that the use of CFRP as external strengthening in deep beam with lap spliced gives best behavior such as increase in stiffness, decrease in deflection, delaying the cracks appearance and reducing the crack width. The reduction in deflection about (14-21 % than the unstrengthened beam and about (5-14 % than the beam with continuous bars near ultimate load. Also, it was observed that the beams with unstrengthened tensile reinforcement lap splices had three types of cracks: flexural, flexural-shear and splitting cracks while the beams with strengthened tensile reinforcement lap splices or continuous bars don’t observe splitting cracks. In the second stage, a numerical analysis of three dimensional finite element analysis was utilized to explore the behavior of the RC deep beams with tensile reinforcement lap splices, in addition to parametric study of many variables. The comparison between the experimental and theoretical results showed reasonable agreement. The average difference of the deflection at service load was less than 5%.

  11. Injection into electron plasma traps

    International Nuclear Information System (INIS)

    Gorgadze, Vladimir; Pasquini, Thomas A.; Fajans, Joel; Wurtele, Jonathan S.


    Computational studies and experimental measurements of plasma injection into a Malmberg-Penning trap reveal that the number of trapped particles can be an order of magnitude higher than predicted by a simple estimates based on a ballistic trapping model. Enhanced trapping is associated with a rich nonlinear dynamics generated by the space-charge forces of the evolving trapped electron density. A particle-in-cell simulation is used to identify the physical mechanisms that lead to the increase in trapped electrons. The simulations initially show strong two-stream interactions between the electrons emitted from the cathode and those reflected off the end plug of the trap. This is followed by virtual cathode oscillations near the injection region. As electrons are trapped, the initially hollow longitudinal phase-space is filled, and the transverse radial density profile evolves so that the plasma potential matches that of the cathode. Simple theoretical arguments are given that describe the different dynamical regimes. Good agreement is found between simulation and theory

  12. Electromagnetic trapping of neutral atoms

    International Nuclear Information System (INIS)

    Metcalf, H.J.


    Cooling and trapping of neutral atoms is a new branch of applied physics that has potential for application in many areas. The authors present an introduction to laser cooling and magnetic trapping. Some basic ideas and fundamental limitations are discussed, and the first successful experiments are reviewed. Trapping a neutral object depends on the interaction between an inhomogeneous electromagnetic field and a multiple moment that results in the exchange of kinetic for potential energy. In neutral atom traps, the potential energy must be stored as internal atomic energy, resulting in two immediate and extremely important consequences. First, the atomic energy levels will necessarily shift as the atoms move in the trap, and, second, practical traps for ground state neutral atoms atr necessarily very shallow compared to thermal energy. This small depth also dictates stringent vacuum requirements because a trapped atom cannot survive a single collision with a thermal energy background gas molecule. Neutral trapping, therefore, depends on substantial cooling of a thermal atomic sample and is inextricably connected with the cooling process

  13. Quantum computing with trapped ions

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, R.J.


    The significance of quantum computation for cryptography is discussed. Following a brief survey of the requirements for quantum computational hardware, an overview of the ion trap quantum computation project at Los Alamos is presented. The physical limitations to quantum computation with trapped ions are analyzed and an assessment of the computational potential of the technology is made.

  14. Oncogenic Alternative Splicing Switches: Role in Cancer Progression and Prospects for Therapy


    Bonomi, Serena; Gallo, Stefania; Catillo, Morena; Pignataro, Daniela; Biamonti, Giuseppe; Ghigna, Claudia


    Alterations in the abundance or activities of alternative splicing regulators generate alternatively spliced variants that contribute to multiple aspects of tumor establishment, progression and resistance to therapeutic treatments. Notably, many cancer-associated genes are regulated through alternative splicing suggesting a significant role of this post-transcriptional regulatory mechanism in the production of oncogenes and tumor suppressors. Thus, the study of alternative splicing in cancer ...

  15. A novel splicing mutation in the V2 vasopressin receptor

    DEFF Research Database (Denmark)

    Kamperis, Konstantinos; Siggaard, C; Herlin, Troels


    as clinical investigations comprising a fluid deprivation test and a 1-deamino-8-D-arginine-vasopressin (dDAVP) infusion test in the study subject and his mother. We found a highly unusual, novel, de novo 1447A-->C point mutation (gDNA), involving the invariable splice acceptor of the second intron...... of the gene in both the affected male (hemizygous) and his mother (heterozygous). This mutation is likely to cause aberrant splicing of the terminal intron of the gene, leading to a non-functional AVP receptor. The clinical studies were consistent with such a hypothesis, as the affected subject had a severe...

  16. Responsible leader behavior in health sectors. (United States)

    Longest, Beaufort


    Purpose The purpose of this paper is to expand attention to responsible leader behavior in the world's health sectors by explaining how this concept applies to health sectors, considering why health sector leaders should behave responsibly, reviewing how they can do so, and asserting potential impact through an applied example. Design/methodology/approach This paper is a viewpoint, reflecting conceptualizations rooted in leadership literature which are then specifically applied to health sectors. A definition of responsible leader behavior is affirmed and applied specifically in health sectors. Conceptualizations and viewpoints about practice of responsible leader behavior in health sectors and potential consequences are then discussed and asserted. Findings Leadership failures and debacles found in health, but more so in other sectors, have led leadership researchers to offer insights, many of them empirical, into the challenges of leadership especially by more clearly delineating responsible leader behavior. Practical implications Much of what has been learned in the research about responsible leader behavior offers pathways for health sector leaders to more fully practice responsible leadership. Social implications This paper asserts and provides a supporting example that greater levels of responsible leader behavior in health sectors hold potentially important societal benefits. Originality/value This paper is the first to apply emerging conceptualizations and early empirical findings about responsible leader behavior specifically to leaders in health sectors.

  17. Electromagnetic trapping of cold atoms

    International Nuclear Information System (INIS)

    Balykin, V.I.; Minogin, V.G.; Letokhov, V.S.


    This review describes the methods of trapping cold atoms in electromagnetic fields and in the combined electromagnetic and gravity fields. We discuss first the basic types of the dipole radiation forces used for cooling and trapping atoms in the laser fields. We outline next the fundamentals of the laser cooling of atoms and classify the temperature limits for basic laser cooling processes. The main body of the review is devoted to discussion of atom traps based on the dipole radiation forces, dipole magnetic forces, combined dipole radiation-magnetic forces, and the forces combined of the dipole radiation-magnetic and gravity forces. Physical fundamentals of atom traps operating as waveguides and cavities for cold atoms are also considered. The review ends with the applications of cold and trapped atoms in atomic, molecular and optical physics. (author)

  18. Establishing the Next Generation at Work : Leader Generativity as a Moderator of the Relationships Between Leader Age, Leader-Member Exchange, and Leadership Success

    NARCIS (Netherlands)

    Zacher, Hannes; Rosing, Kathrin; Henning, Thomas; Frese, Michael

    In this study, the authors investigated leader generativity as a moderator of the relationships between leader age, leader-member exchange, and three criteria of leadership success (follower perceptions of leader effectiveness, follower satisfaction with leader, and follower extra effort). Data came

  19. Leaders break ground for INFINITY (United States)


    Community leaders from Mississippi and Louisiana break ground for the new INFINITY at NASA Stennis Space Center facility during a Nov. 20 ceremony. Groundbreaking participants included (l to r): Gottfried Construction representative John Smith, Mississippi Highway Commissioner Wayne Brown, INFINITY board member and Apollo 13 astronaut Fred Haise, Stennis Director Gene Goldman, Studio South representative David Hardy, Leo Seal Jr. family representative Virginia Wagner, Hancock Bank President George Schloegel, Mississippi Rep. J.P. Compretta, Mississippi Band of Choctaw Indians representative Charlie Benn and Louisiana Sen. A.G. Crowe.

  20. ISVASE: identification of sequence variant associated with splicing event using RNA-seq data. (United States)

    Aljohi, Hasan Awad; Liu, Wanfei; Lin, Qiang; Yu, Jun; Hu, Songnian


    Exon recognition and splicing precisely and efficiently by spliceosome is the key to generate mature mRNAs. About one third or a half of disease-related mutations affect RNA splicing. Software PVAAS has been developed to identify variants associated with aberrant splicing by directly using RNA-seq data. However, it bases on the assumption that annotated splicing site is normal splicing, which is not true in fact. We develop the ISVASE, a tool for specifically identifying sequence variants associated with splicing events (SVASE) by using RNA-seq data. Comparing with PVAAS, our tool has several advantages, such as multi-pass stringent rule-dependent filters and statistical filters, only using split-reads, independent sequence variant identification in each part of splicing (junction), sequence variant detection for both of known and novel splicing event, additional exon-exon junction shift event detection if known splicing events provided, splicing signal evaluation, known DNA mutation and/or RNA editing data supported, higher precision and consistency, and short running time. Using a realistic RNA-seq dataset, we performed a case study to illustrate the functionality and effectiveness of our method. Moreover, the output of SVASEs can be used for downstream analysis such as splicing regulatory element study and sequence variant functional analysis. ISVASE is useful for researchers interested in sequence variants (DNA mutation and/or RNA editing) associated with splicing events. The package is freely available at .

  1. Interplay between DMD Point Mutations and Splicing Signals in Dystrophinopathy Phenotypes (United States)

    Juan-Mateu, Jonàs; González-Quereda, Lidia; Rodríguez, Maria José; Verdura, Edgard; Lázaro, Kira; Jou, Cristina; Nascimento, Andrés; Jiménez-Mallebrera, Cecilia; Colomer, Jaume; Monges, Soledad; Lubieniecki, Fabiana; Foncuberta, Maria Eugenia; Pascual-Pascual, Samuel Ignacio; Molano, Jesús; Baiget, Montserrat; Gallano, Pia


    DMD nonsense and frameshift mutations lead to severe Duchenne muscular dystrophy while in-frame mutations lead to milder Becker muscular dystrophy. Exceptions are found in 10% of cases and the production of alternatively spliced transcripts is considered a key modifier of disease severity. Several exonic mutations have been shown to induce exon-skipping, while splice site mutations result in exon-skipping or activation of cryptic splice sites. However, factors determining the splicing pathway are still unclear. Point mutations provide valuable information regarding the regulation of pre-mRNA splicing and elements defining exon identity in the DMD gene. Here we provide a comprehensive analysis of 98 point mutations related to clinical phenotype and their effect on muscle mRNA and dystrophin expression. Aberrant splicing was found in 27 mutations due to alteration of splice sites or splicing regulatory elements. Bioinformatics analysis was performed to test the ability of the available algorithms to predict consequences on mRNA and to investigate the major factors that determine the splicing pathway in mutations affecting splicing signals. Our findings suggest that the splicing pathway is highly dependent on the interplay between splice site strength and density of regulatory elements. PMID:23536893

  2. Interplay between DMD point mutations and splicing signals in Dystrophinopathy phenotypes.

    Directory of Open Access Journals (Sweden)

    Jonàs Juan-Mateu

    Full Text Available DMD nonsense and frameshift mutations lead to severe Duchenne muscular dystrophy while in-frame mutations lead to milder Becker muscular dystrophy. Exceptions are found in 10% of cases and the production of alternatively spliced transcripts is considered a key modifier of disease severity. Several exonic mutations have been shown to induce exon-skipping, while splice site mutations result in exon-skipping or activation of cryptic splice sites. However, factors determining the splicing pathway are still unclear. Point mutations provide valuable information regarding the regulation of pre-mRNA splicing and elements defining exon identity in the DMD gene. Here we provide a comprehensive analysis of 98 point mutations related to clinical phenotype and their effect on muscle mRNA and dystrophin expression. Aberrant splicing was found in 27 mutations due to alteration of splice sites or splicing regulatory elements. Bioinformatics analysis was performed to test the ability of the available algorithms to predict consequences on mRNA and to investigate the major factors that determine the splicing pathway in mutations affecting splicing signals. Our findings suggest that the splicing pathway is highly dependent on the interplay between splice site strength and density of regulatory elements.

  3. Passion in today's health care leaders. (United States)

    Piper, Llewellyn E


    Passion in today's health care leaders is essential as health care organizations face increasing demands for survival. Leaders in health care have been educated, selected, promoted, and retained based on their analytical and creativity skills. Today's health care leaders must also have emotional intelligence. Emotional intelligence is primal for passion. Emotional intelligence, which leads to passion, is crucial to the survivability of today's health care organizations. In order for health care organizations to go from good to great, the leader must inspire followers through passion. This article encourages health care leaders to gain awareness of emotional intelligence and to use emotional intelligence as part of their leadership to inspire passion. Through passion, leaders and followers become more motivated to accomplish the health care mission of serving others.

  4. Trapped quintessential inflation

    International Nuclear Information System (INIS)

    Bueno Sanchez, J.C.; Dimopoulos, K.


    Quintessential inflation is studied using a string modulus as the inflaton-quintessence field. The modulus begins its evolution at the steep part of its scalar potential, which is due to non-perturbative effects (e.g. gaugino condensation). It is assumed that the modulus crosses an enhanced symmetry point (ESP) in field space. Particle production at the ESP temporarily traps the modulus resulting in a brief period of inflation. More inflation follows, due to the flatness of the potential, since the ESP generates either an extremum (maximum or minimum) or a flat inflection point in the scalar potential. Eventually, the potential becomes steep again and inflation is terminated. After reheating the modulus freezes due to cosmological friction at a large value, such that its scalar potential is dominated by contributions due to fluxes in the extra dimensions or other effects. The modulus remains frozen until the present, when it can become quintessence and account for the dark energy necessary to explain the observed accelerated expansion

  5. Trap-mulching Argentine ants. (United States)

    Silverman, Jules; Sorenson, Clyde E; Waldvogel, Michael G


    Argentine ant, Linepithema humile (Mayr), management is constrained, in large part, by polydomy where nestmates are distributed extensively across urban landscapes, particularly within mulch. Management with trap-mulching is a novel approach derived from trap-cropping where ants are repelled from a broad domain of nest sites to smaller defined areas, which are subsequently treated with insecticide. This concept was field-tested with mulch surrounding ornamental trees replaced with a narrow band of pine (Pinus spp.) needle mulch (trap) within a much larger patch of repellent aromatic cedar (Juniperus spp.) mulch. After ants reestablished around the trees, the pine needle mulch band was treated with 0.06% fipronil (Termidor). Poor results were obtained when the trap extended from the tree trunk to the edge of the mulched area. When the trap was applied as a circular band around the tree trunk reductions in the number of foraging ants were recorded through 14 d compared with an untreated mulch control, but not for longer periods. Reductions in the number of ant nests within mulch were no different between the trap mulch and any of the other treatments. We conclude that trap-mulching offers limited benefits, and that successful management of Argentine ants will require implementation of complementary or perhaps alternative strategies.

  6. Why the world needs moral leaders

    DEFF Research Database (Denmark)

    Mehlsen, Camilla


    The educational system plays a huge role in developing the moral leaders of tomorrow. The Quarterly takes a closer look at diversity in South Africa's schools, at the young generation in China, and at the making of moral leaders with both a global and local mindset.......The educational system plays a huge role in developing the moral leaders of tomorrow. The Quarterly takes a closer look at diversity in South Africa's schools, at the young generation in China, and at the making of moral leaders with both a global and local mindset....

  7. Developing Socially Responsible Leaders in Academic Settings (United States)

    Cauthen, T. W., III


    This chapter begins the exploration of what leadership education is through examining the relationship between educational involvement and academic autonomy in the development of socially responsible leaders.

  8. Competitive Pricing by a Price Leader


    Abhik Roy; Dominique M. Hanssens; Jagmohan S. Raju


    We examine the problem of pricing in a market where one brand acts as a price leader. We develop a procedure to estimate a leader's price rule, which is optimal given a sales target objective, and allows for the inclusion of demand forecasts. We illustrate our estimation procedure by calibrating this optimal price rule for both the leader and the follower using data on past sales and prices from the mid-size sedan segment of the U.S. automobile market. Our results suggest that a leader-follow...

  9. Addressing Deficiencies in Army Civilian Leader Development

    National Research Council Canada - National Science Library

    Keller, Jonathan S


    .... A well managed, comparable, and integrated Army leader training, education, and development framework, designed to create shared and combined developmental experiences, is essential for growing...

  10. fruitless alternative splicing and sex behaviour in insects

    Indian Academy of Sciences (India)

    In Drosophila melanogaster, male courtship requires proteins encoded by the fruitless (fru) gene that are produced in different sex-specific isoforms via alternative splicing. Drosophila mutant flies with loss-of-function alleles of the fru gene exhibit blocked male courtship behaviour. However, various individual steps in the ...

  11. fruitless alternative splicing and sex behaviour in insects: an ancient ...

    Indian Academy of Sciences (India)

    In Drosophila melanogaster, male courtship requires proteins encoded by the fruitless (fru) gene that are produced in different sex-specific isoforms via alternative splicing. Drosophila mutant flies with loss-of-function alleles of the fru gene exhibit blocked male courtship behaviour. However, various individual steps in the ...

  12. Splicing aberrations caused by constitutional RB1 gene mutations in ...

    Indian Academy of Sciences (India)

    Analysis of RB1 mRNA from blood leukocytes of patients with retinoblastoma identified the effects of mutations involving consensus splice site, exonic substitution and whole-exon deletions identified in genomic DNA of these patients. In addition, this study identified mutations in cases in which no mutations were detectable ...

  13. Multishot diffusion-weighted SPLICE PROPELLER MRI of the abdomen. (United States)

    Deng, Jie; Omary, Reed A; Larson, Andrew C


    Multishot FSE (fast spin echo)-based diffusion-weighted (DW)-PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) MRI offers the potential to reduce susceptibility artifacts associated with single-shot DW-EPI (echo-planar imaging) approaches. However, DW-PROPELLER in the abdomen is challenging due to the large field-of-view and respiratory motion during DW preparation. Incoherent signal phase due to motion will violate the Carr-Purcell-Meiboom-Gill (CPMG) conditions, leading to destructive interference between spin echo and stimulated echo signals and consequent signal cancellation. The SPLICE (split-echo acquisition of FSE signals) technique can mitigate non-CPMG artifacts in FSE-based sequences. For SPLICE, spin echo and stimulated echo are separated by using imbalanced readout gradients and extended acquisition window. Two signal families each with coherent phase properties are acquired at different intervals within the readout window. Separate reconstruction of these two signal families can avoid destructive phase interference. Phantom studies were performed to validate signal phase properties with different initial magnetization phases. This study evaluated the feasibility of combining SPLICE and PROPELLER for DW imaging of the abdomen. It is demonstrated that DW-SPLICE-PROPELLER can effectively mitigate non-CPMG artifacts and improve DW image quality and apparent diffusion coefficient (ADC) map homogeneity. (c) 2008 Wiley-Liss, Inc.

  14. Alanine repeats influence protein localization in splicing speckles and paraspeckles. (United States)

    Chang, Shuo-Hsiu; Chang, Wei-Lun; Lu, Chia-Chen; Tarn, Woan-Yuh


    Mammalian splicing regulatory protein RNA-binding motif protein 4 (RBM4) has an alanine repeat-containing C-terminal domain (CAD) that confers both nuclear- and splicing speckle-targeting activities. Alanine-repeat expansion has pathological potential. Here we show that the alanine-repeat tracts influence the subnuclear targeting properties of the RBM4 CAD in cultured human cells. Notably, truncation of the alanine tracts redistributed a portion of RBM4 to paraspeckles. The alanine-deficient CAD was sufficient for paraspeckle targeting. On the other hand, alanine-repeat expansion reduced the mobility of RBM4 and impaired its splicing activity. We further took advantage of the putative coactivator activator (CoAA)-RBM4 conjoined splicing factor, CoAZ, to investigate the function of the CAD in subnuclear targeting. Transiently expressed CoAZ formed discrete nuclear foci that emerged and subsequently separated-fully or partially-from paraspeckles. Alanine-repeat expansion appeared to prevent CoAZ separation from paraspeckles, resulting in their complete colocalization. CoAZ foci were dynamic but, unlike paraspeckles, were resistant to RNase treatment. Our results indicate that the alanine-rich CAD, in conjunction with its conjoined RNA-binding domain(s), differentially influences the subnuclear localization and biogenesis of RBM4 and CoAZ. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Long-range RNA pairings contribute to mutually exclusive splicing. (United States)

    Yue, Yuan; Yang, Yun; Dai, Lanzhi; Cao, Guozheng; Chen, Ran; Hong, Weiling; Liu, Baoping; Shi, Yang; Meng, Yijun; Shi, Feng; Xiao, Mu; Jin, Yongfeng


    Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of the Dscam exon cluster. Here, we reveal a molecular model for the regulation of the mutually exclusive splicing of the serpent pre-mRNA based on competition between upstream and downstream RNA pairings. Such dual RNA pairings confer fine tuning of the inclusion of alternative exons. Moreover, we demonstrate that the splicing outcome of alternative exons is mediated in relative pairing strength-correlated mode. Combined comparative genomics analysis and experimental evidence revealed similar bidirectional structural architectures in exon clusters 4 and 9 of the Dscam gene. Our findings provide a novel mechanistic framework for the regulation of mutually exclusive splicing and may offer potentially applicable insights into long-range RNA-RNA interactions in gene regulatory networks. © 2015 Yue et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  16. CD44 splice variants as prognostic markers in colorectal cancer

    NARCIS (Netherlands)

    Wielenga, V. J.; van der Voort, R.; Mulder, J. W.; Kruyt, P. M.; Weidema, W. F.; Oosting, J.; Seldenrijk, C. A.; van Krimpen, C.; Offerhaus, G. J.; Pals, S. T.


    BACKGROUND: Splice variants of CD44 play a causal role in the metastatic spread of pancreatic carcinoma in the rat. In previous studies we have shown that homologues of these CD44 isoforms (CD44v6) are overexpressed during colorectal tumorigenesis in man and that CD44v6 overexpression is associated

  17. Unusual structure and splicing pattern of the vertebrate ...

    Indian Academy of Sciences (India)



    Mar 8, 2018 ... coding section of SLC25A3 which occurred in fish and is conserved in amphibia, birds and mammals. Further, we discuss the way the splicing mechanism compensates. Rosa Calvello and Antonia Cianciulli contributed equally to this work. for the potentially harmful consequences of this 'genomic glitch'.

  18. Splicing aberrations caused by constitutional RB1 gene mutations in ...

    Indian Academy of Sciences (India)

    . [Parsam VL, Ali MJ, Honavar SG, Vemuganti GK and Kannabiran C 2011 Splicing aberrations caused by constitutional RB1 gene mutations in retinoblastoma. J. Biosci. 36 281–287] DOI 10.1007/s12038-011-9062-9. 1. Introduction.

  19. Splicing aberrations caused by constitutional RB1 gene mutations in ...

    Indian Academy of Sciences (India)

    Analysis of RB1 mRNA from blood leukocytes of patients with retinoblastoma identified the effects of mutations involving consensus splice site, .... bilateral Rb. Genomic DNA analysis from peripheral blood was as described by Parsam .... the patterns are not always the same in different studies (Klutz et al. 2002; Taylor et al.

  20. A reservoir trap for antiprotons

    CERN Document Server

    Smorra, Christian; Franke, Kurt; Nagahama, Hiroki; Schneider, Georg; Higuchi, Takashi; Van Gorp, Simon; Blaum, Klaus; Matsuda, Yasuyuki; Quint, Wolfgang; Walz, Jochen; Yamazaki, Yasunori; Ulmer, Stefan


    We have developed techniques to extract arbitrary fractions of antiprotons from an accumulated reservoir, and to inject them into a Penning-trap system for high-precision measurements. In our trap-system antiproton storage times > 1.08 years are estimated. The device is fail-safe against power-cuts of up to 10 hours. This makes our planned comparisons of the fundamental properties of protons and antiprotons independent from accelerator cycles, and will enable us to perform experiments during long accelerator shutdown periods when background magnetic noise is low. The demonstrated scheme has the potential to be applied in many other precision Penning trap experiments dealing with exotic particles.

  1. Cytoplasmic viral RNA-dependent RNA polymerase disrupts the intracellular splicing machinery by entering the nucleus and interfering with Prp8.

    Directory of Open Access Journals (Sweden)

    Yen-Chin Liu


    Full Text Available The primary role of cytoplasmic viral RNA-dependent RNA polymerase (RdRp is viral genome replication in the cellular cytoplasm. However, picornaviral RdRp denoted 3D polymerase (3D(pol also enters the host nucleus, where its function remains unclear. In this study, we describe a novel mechanism of viral attack in which 3D(pol enters the nucleus through the nuclear localization signal (NLS and targets the pre-mRNA processing factor 8 (Prp8 to block pre-mRNA splicing and mRNA synthesis. The fingers domain of 3D(pol associates with the C-terminal region of Prp8, which contains the Jab1/MPN domain, and interferes in the second catalytic step, resulting in the accumulation of the lariat form of the splicing intermediate. Endogenous pre-mRNAs trapped by the Prp8-3D(pol complex in enterovirus-infected cells were identified and classed into groups associated with cell growth, proliferation, and differentiation. Our results suggest that picornaviral RdRp disrupts pre-mRNA splicing processes, that differs from viral protease shutting off cellular transcription and translation which contributes to the pathogenesis of viral infection.

  2. The splicing fate of plant SPO11 genes

    Directory of Open Access Journals (Sweden)

    Thorben eSprink


    Full Text Available Towards the global understanding of plant meiosis, it seems to be essential to decipher why all as yet sequenced plants need or at least encode for two different meiotic SPO11 genes. This is in contrast to mammals and fungi, where only one SPO11 is present. Both SPO11 in plants are essential for the initiation of double strand breaks (DSBs during the meiotic prophase. In nearly all eukaryotic organisms DSB induction by SPO11 leads to meiotic DSB repair, thereby ensuring the formation of a necessary number of crossovers (CO as physical connections between the allelic chromosomes. We aim to investigate the specific functions and evolution of both SPO11 genes in land plants. Therefore, we identified and cloned the respective orthologous genes from Brassica rapa, Carica papaya, Oryza sativa and Physcomitrella patens. In parallel we determined the full length cDNA sequences of SPO11-1 and -2 from all of these plants by RT-PCR. During these experiments we observed that the analyzed plants exhibit a pattern of aberrant splicing products of both SPO11 mRNAs. Such an aberrant splicing has previously been described for Arabidopsis and therefore seems to be conserved throughout evolution. Most of the splicing forms of SPO11-1 and -2 seem to be non functional as they either showed intron retention or shortened exons accompanied by a frameshift leading to premature termination codons (PTCs in most cases. Nevertheless, we could detect one putative functional alternatively spliced mRNA for SPO11-1 and -2 each, indicating that splicing of SPO11 does not depend only on the gene sequence but also on the plant species and that it might play a regulatory role.

  3. Alternative Splicing of NOX4 in the Failing Human Heart

    Directory of Open Access Journals (Sweden)

    Zoltán V. Varga


    Full Text Available Increased oxidative stress is a major contributor to the development and progression of heart failure, however, our knowledge on the role of the distinct NADPH oxidase (NOX isoenzymes, especially on NOX4 is controversial. Therefore, we aimed to characterize NOX4 expression in human samples from healthy and failing hearts. Explanted human heart samples (left and right ventricular, and septal regions were obtained from patients suffering from heart failure of ischemic or dilated origin. Control samples were obtained from donor hearts that were not used for transplantation. Deep RNA sequencing of the cardiac transcriptome indicated extensive alternative splicing of the NOX4 gene in heart failure as compared to samples from healthy donor hearts. Long distance PCR analysis with a universal 5′-3′ end primer pair, allowing amplification of different splice variants, confirmed the presence of the splice variants. To assess translation of the alternatively spliced transcripts we determined protein expression of NOX4 by using a specific antibody recognizing a conserved region in all variants. Western blot analysis showed up-regulation of the full-length NOX4 in ischemic cardiomyopathy samples and confirmed presence of shorter isoforms both in control and failing samples with disease-associated expression pattern. We describe here for the first time that NOX4 undergoes extensive alternative splicing in human hearts which gives rise to the expression of different enzyme isoforms. The full length NOX4 is significantly upregulated in ischemic cardiomyopathy suggesting a role for NOX4 in ROS production during heart failure.

  4. A Comprehensive Analysis of Alternative Splicing in Paleopolyploid Maize

    Directory of Open Access Journals (Sweden)

    Wenbin Mei


    Full Text Available Identifying and characterizing alternative splicing (AS enables our understanding of the biological role of transcript isoform diversity. This study describes the use of publicly available RNA-Seq data to identify and characterize the global diversity of AS isoforms in maize using the inbred lines B73 and Mo17, and a related species, sorghum. Identification and characterization of AS within maize tissues revealed that genes expressed in seed exhibit the largest differential AS relative to other tissues examined. Additionally, differences in AS between the two genotypes B73 and Mo17 are greatest within genes expressed in seed. We demonstrate that changes in the level of alternatively spliced transcripts (intron retention and exon skipping do not solely reflect differences in total transcript abundance, and we present evidence that intron retention may act to fine-tune gene expression across seed development stages. Furthermore, we have identified temperature sensitive AS in maize and demonstrate that drought-induced changes in AS involve distinct sets of genes in reproductive and vegetative tissues. Examining our identified AS isoforms within B73 × Mo17 recombinant inbred lines (RILs identified splicing QTL (sQTL. The 43.3% of cis-sQTL regulated junctions are actually identified as alternatively spliced junctions in our analysis, while 10 Mb windows on each side of 48.2% of trans-sQTLs overlap with splicing related genes. Using sorghum as an out-group enabled direct examination of loss or conservation of AS between homeologous genes representing the two subgenomes of maize. We identify several instances where AS isoforms that are conserved between one maize homeolog and its sorghum ortholog are absent from the second maize homeolog, suggesting that these AS isoforms may have been lost after the maize whole genome duplication event. This comprehensive analysis provides new insights into the complexity of AS in maize.

  5. Urban fall traps

    Directory of Open Access Journals (Sweden)

    Vera Lucia de Almeida Valsecchi


    Full Text Available Objectives: To evaluate the repercussion of falls in the elderly peoplewho live in the city of São Paulo and address - though synthetically- some questions regarding the city and its relation to aging and thequality of life of the elderly. Methods: This is a qualitative study. As fordata collection, “in-depth individual interviews” were applied. Selectionof subjects was guided by a procedure named as “network”. Results:Ten interviews were performed, nine with elderly individuals who werevictims of falls and one with a public authority representative. Dataresulting from interviews confirmed that significant changes occurin live of the elderly, who are victims of what has been called “urbantraps”, and that, by extrapolating mobility and dependence contexts,invade feelings, emotions and desires. The inappropriate environmentprovided by the city of São Paulo is confirmed by absence of adequateurban planning and lack of commitment of public authorities. It alsorevealed that the particular way of being old and living an elderlylife, in addition to right to citizenship, is reflected by major or lesserdifficulties imposed to the elderly to fight for their rights and have theirpublic space respected. Conclusion: The city of São Paulo is not anideal locus for an older person to live in. To the traps that are found inpublic places one can add those that are found in private places andthat contribute to the hard experience of falls among the elderly, anexperience that is sometimes fatal. In Brazil, the attention is basicallyfocused on the consequences of falls and not on prevention, by meansof urban planning that should meet the needs of the most vulnerablegroups - the physically disabled and the elderly.

  6. Innovation: the classic traps. (United States)

    Kanter, Rosabeth Moss


    these traps.

  7. Rapid screening of yeast mutants with reporters identifies new splicing phenotypes. (United States)

    Dreumont, Natacha; Séraphin, Bertrand


    Nuclear precursor mRNA splicing requires the stepwise assembly of a large complex, the spliceosome. Recent large-scale analyses, including purification of splicing complexes, high-throughput genetic screens and interactomic studies, have linked numerous factors to this dynamic process, including a well-defined core conserved from yeast to human. Intriguingly, despite extensive studies, no splicing defects were reported for some of the corresponding yeast mutants. To resolve this paradox, we screened a collection of viable yeast strains carrying mutations in splicing-related factors with a set of reporters including artificial constructs carrying competing splice sites. Previous analyses have indeed demonstrated that this strategy identifies yeast factors able to regulate alternative splicing and whose properties are conserved in human cells. The method, sensitive to subtle defects, revealed new splicing phenotypes for most analyzed factors such as the Urn1 protein. Interestingly, a mutant of PRP8 specifically lacking an N-terminal proline-rich region stimulated the splicing of a reporter containing competing branchpoint/3' splice site regions. Thus, using appropriate reporters, yeast can be used to quickly delineate the effect of various factors on splicing and identify those with the propensity to regulate alternative splicing events. © 2013 FEBS.

  8. Transcription rate strongly affects splicing fidelity and cotranscriptionality in budding yeast. (United States)

    Aslanzadeh, Vahid; Huang, Yuanhua; Sanguinetti, Guido; Beggs, Jean D


    The functional consequences of alternative splicing on altering the transcription rate have been the subject of intensive study in mammalian cells but less is known about effects of splicing on changing the transcription rate in yeast. We present several lines of evidence showing that slow RNA polymerase II elongation increases both cotranscriptional splicing and splicing efficiency and that faster elongation reduces cotranscriptional splicing and splicing efficiency in budding yeast, suggesting that splicing is more efficient when cotranscriptional. Moreover, we demonstrate that altering the RNA polymerase II elongation rate in either direction compromises splicing fidelity, and we reveal that splicing fidelity depends largely on intron length together with secondary structure and splice site score. These effects are notably stronger for the highly expressed ribosomal protein coding transcripts. We propose that transcription by RNA polymerase II is tuned to optimize the efficiency and accuracy of ribosomal protein gene expression, while allowing flexibility in splice site choice with the nonribosomal protein transcripts. © 2018 Aslanzadeh et al.; Published by Cold Spring Harbor Laboratory Press.

  9. A 5' splice site enhances the recruitment of basal transcription initiation factors in vivo

    DEFF Research Database (Denmark)

    Damgaard, Christian Kroun; Kahns, Søren; Lykke-Andersen, Søren


    Transcription and pre-mRNA splicing are interdependent events. Although mechanisms governing the effects of transcription on splicing are becoming increasingly clear, the means by which splicing affects transcription remain elusive. Using cell lines stably expressing HIV-1 or β-globin mRNAs, harb...... a promoter-proximal 5′ splice site via its U1 snRNA interaction can feed back to stimulate transcription initiation by enhancing preinitiation complex assembly.......Transcription and pre-mRNA splicing are interdependent events. Although mechanisms governing the effects of transcription on splicing are becoming increasingly clear, the means by which splicing affects transcription remain elusive. Using cell lines stably expressing HIV-1 or β-globin mRNAs......, harboring wild-type or various 5′ splice site mutations, we demonstrate a strong positive correlation between splicing efficiency and transcription activity. Interestingly, a 5′ splice site can stimulate transcription even in the absence of splicing. Chromatin immunoprecipitation experiments show enhanced...

  10. Funnel traps capture a higher proportion of juvenile Great Tits Parus major than automatic traps (United States)

    Senar, J.C.; Domenech, J.; Conroy, M.J.


    We compared capture rates of Great Tits at funnel traps, where several birds can be captured at once so that some decoy effect may appear, to those obtained at automatic traps, where only one bird can be trapped at a time, at trapping stations in northeastern Spain. Juvenile birds were mainly captured at funnel traps (79% of juvenile captures), whereas adult plumaged birds were captured at both types of traps (51% of captures were at the funnel traps) (test between ages, Pfunnel traps, which may be acting as decoy traps, and thus are vulnerable to the same kinds of biases (eg age or body condition) that have been previously documented for decoy traps.

  11. Effect of Chord Splice Joints on Force Distribution and Deformations in Trusses with Punched Metal Plate Fasteners

    DEFF Research Database (Denmark)

    Ellegaard, Peter


    - their real behaviour is semi-rigid. The influence of splice joints on the distribution of member forces and rotations in the splice joints is investigated in this paper. A finite element program, TrussLab, where the splice joints are given semi-rigid properties is used to analyse the effect of splice joints...

  12. Leader emergence through interpersonal neural synchronization. (United States)

    Jiang, Jing; Chen, Chuansheng; Dai, Bohan; Shi, Guang; Ding, Guosheng; Liu, Li; Lu, Chunming


    The neural mechanism of leader emergence is not well understood. This study investigated (i) whether interpersonal neural synchronization (INS) plays an important role in leader emergence, and (ii) whether INS and leader emergence are associated with the frequency or the quality of communications. Eleven three-member groups were asked to perform a leaderless group discussion (LGD) task, and their brain activities were recorded via functional near infrared spectroscopy (fNIRS)-based hyperscanning. Video recordings of the discussions were coded for leadership and communication. Results showed that the INS for the leader-follower (LF) pairs was higher than that for the follower-follower (FF) pairs in the left temporo-parietal junction (TPJ), an area important for social mentalizing. Although communication frequency was higher for the LF pairs than for the FF pairs, the frequency of leader-initiated and follower-initiated communication did not differ significantly. Moreover, INS for the LF pairs was significantly higher during leader-initiated communication than during follower-initiated communications. In addition, INS for the LF pairs during leader-initiated communication was significantly correlated with the leaders' communication skills and competence, but not their communication frequency. Finally, leadership could be successfully predicted based on INS as well as communication frequency early during the LGD (before half a minute into the task). In sum, this study found that leader emergence was characterized by high-level neural synchronization between the leader and followers and that the quality, rather than the frequency, of communications was associated with synchronization. These results suggest that leaders emerge because they are able to say the right things at the right time.

  13. How Can the Skills of Early Years Leaders Support Other Leaders in a Primary School Setting? (United States)

    Mistry, Malini; Sood, Krishan


    This study investigated the leadership skills Early Years leaders demonstrated through their daily practice of teaching, assessing and teamwork within their setting. It explored how revealing the potential of Early Years leaders could have a positive impact on the leadership practice of other leaders in the same setting to improve pupil outcomes.…

  14. Leader trust and employee voice : The moderating role of empowering leader behaviors

    NARCIS (Netherlands)

    Gao, L.; Janssen, O.; Shi, K.

    This paper explored how employees' trust in their leader interacted with empowering leader behaviors in promoting employee voice. Using data collected from 314 employees in the telecommunication industry in China, we found that the relationship between leader trust and employee voice became more

  15. Twenty-Two Hispanic Leaders Discuss Poverty: Results from the Hispanic Leaders Study. Final Version. (United States)

    Quiroz, Julia Teresa

    This study examines the perceptions of 22 national Hispanic American leaders about poverty among Hispanics. Eleven of the leaders were Mexican American; five were Puerto Rican; four were Cuban American; one was Central American; and one was South American. Twelve of the leaders were heads of public interest organizations; six were members of…

  16. Leader self-sacrifice and leadership effectiveness: The moderating role of leader prototypicality

    NARCIS (Netherlands)

    van Knippenberg, B.M.; van Knippenberg, D.


    Self-sacrificing behavior of the leader and the extent to which the leader is representative of the group (i.e., group prototypical) are proposed to interact to influence leadership effectiveness. The authors expected self-sacrificing leaders to be considered more effective and to be able to push

  17. Mammalian tissues defective in nonsense-mediated mRNA decay display highly aberrant splicing patterns

    DEFF Research Database (Denmark)

    Weischenfeldt, Joachim Lütken; Waage, Johannes Eichler; Tian, Geng


    ABSTRACT: BACKGROUND: Nonsense-mediated mRNA decay (NMD) affects the outcome of alternative splicing by degrading mRNA isoforms with premature termination codons. Splicing regulators constitute important NMD targets; however, the extent to which loss of NMD causes extensive deregulation...... of alternative splicing has not previously been assayed in a global, unbiased manner. Here, we combine mouse genetics and RNA-seq to provide the first in vivo analysis of the global impact of NMD on splicing patterns in two primary mouse tissues ablated for the NMD factor UPF2. RESULTS: We developed...... importance, the latter events are associated with high intronic conservation. CONCLUSIONS: Our data demonstrate that NMD regulates alternative splicing outcomes through an intricate web of splicing regulators and that its loss leads to the deregulation of a panoply of splicing events, providing novel...

  18. Effect of fiber blending ratios of cotton/polyester yarns on retained splice diameter (United States)

    Çelik, H. İ.; Kaynak, H. K.


    The most important performance parameters of splicing are obtaining adequate strength and appearance at the splice point for all processing requirements. The diameter of spliced portion effects not only appearance of the splice joints but also physical characteristics such as packing density, strength, specific volume of the yarn. In this study, the effect of cotton/polyester fiber blend ratios on spliced portion diameter at different slicing air pressures was investigated. For this aim, three yarn samples 100% cotton, 80-20% CO-PES and 50- 50% CO-PES were produced with 40/1 Ne. Each yarn samples was spliced at three different pressures; 4 bar, 5 bar and 6 bar. The diameters of spliced portion and retained yarns were measured by using ImageJ program and the results were analyzed statistically.

  19. The physician leader as logotherapist. (United States)

    Washburn, E R


    Today's physicians feel helpless and angry about changing conditions in the medical landscape. This is due, in large part, to our postmodernist world view and the influence of corporations on medical practice. The life and work of existentialist psychiatrist Viktor Frankl is proposed as a role model for physicians to take back control of their profession. Physician leaders are in the best position to bring the teachings and insight of Frankl's logotherapy to rank-and-file physicians in all practice settings, as well as into the board rooms of large medical corporations. This article considers the spiritual and moral troubles of American medicine, Frankl's answer to that affliction, and the implications of logotherapy for physician organizations and leadership. Physician executives are challenged to take up this task.

  20. IS and Business Leaders' Strategizing

    DEFF Research Database (Denmark)

    Hansen, Anne Mette

    IS strategy has become an important focus in both research and practice over the past decades. In research, IS strategy has traditionally been viewed as the use of IT to support a business strategy or the master plan of the IS function. However, more recent IS strategy research has increasingly...... in and utilization of IT within the organization. This dissertation is positioned in relation to this recent IS strategy research. In practice, IS and business leaders’ constant development and repositioning of IS strategic objectives has become increasingly important over time as organizations face turbulent...... business environments characterized by changes in market demands, technology options, and government regulations. Under such dynamic conditions, IS and business leaders must constantly strategize and set new IS strategic objectives so that they can retain and improve innovation, competitiveness...

  1. Trapping Triatominae in Silvatic Habitats

    Directory of Open Access Journals (Sweden)

    Noireau François


    Full Text Available Large-scale trials of a trapping system designed to collect silvatic Triatominae are reported. Live-baited adhesive traps were tested in various ecosystems and different triatomine habitats (arboreal and terrestrial. The trials were always successful, with a rate of positive habitats generally over 20% and reaching 48.4% for palm trees of the Amazon basin. Eleven species of Triatominae belonging to the three genera of public health importance (Triatoma, Rhodnius and Panstrongylus were captured. This trapping system provides an effective way to detect the presence of triatomines in terrestrial and arboreal silvatic habitats and represents a promising tool for ecological studies. Various lines of research are contemplated to improve the performance of this trapping system.

  2. Evaporative cooling of trapped atoms

    International Nuclear Information System (INIS)

    Ketterle, W.; Van Druten, N.J.


    This report discusses the following topics on evaporative cooling of trapped atoms: Theoretical models for evaporative cooling; the role of collisions for real atoms; experimental techniques and summary of evaporative cooling experiments. 166 refs., 6 figs., 3 tabs

  3. Diversity of insect trypanosomatids assessed from the spliced leader RNA and 5S rRNA genes and intergenic regions

    Czech Academy of Sciences Publication Activity Database

    Podlipaev, Sergei; Sturm, N. R.; Fiala, Ivan; Fernandes, O.; Westenberger, S. J.; Dollet, M.; Campbell, D. A.; Lukeš, Julius


    Roč. 51, č. 3 (2004), s. 283-290 ISSN 1066-5234 Grant - others:European Community(XE) QLK 2-CT-2001-01810 Institutional research plan: CEZ:AV0Z6022909 Keywords : Kinetoplastida * phylogeny * Trypanosomatidae Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.403, year: 2004

  4. Oriented scanning is the leading mechanism underlying 5' splice site selection in mammals.

    Directory of Open Access Journals (Sweden)

    Keren Borensztajn


    Full Text Available Splice site selection is a key element of pre-mRNA splicing. Although it is known to involve specific recognition of short consensus sequences by the splicing machinery, the mechanisms by which 5' splice sites are accurately identified remain controversial and incompletely resolved. The human F7 gene contains in its seventh intron (IVS7 a 37-bp VNTR minisatellite whose first element spans the exon7-IVS7 boundary. As a consequence, the IVS7 authentic donor splice site is followed by several cryptic splice sites identical in sequence, referred to as 5' pseudo-sites, which normally remain silent. This region, therefore, provides a remarkable model to decipher the mechanism underlying 5' splice site selection in mammals. We previously suggested a model for splice site selection that, in the presence of consecutive splice consensus sequences, would stimulate exclusively the selection of the most upstream 5' splice site, rather than repressing the 3' following pseudo-sites. In the present study, we provide experimental support to this hypothesis by using a mutational approach involving a panel of 50 mutant and wild-type F7 constructs expressed in various cell types. We demonstrate that the F7 IVS7 5' pseudo-sites are functional, but do not compete with the authentic donor splice site. Moreover, we show that the selection of the 5' splice site follows a scanning-type mechanism, precluding competition with other functional 5' pseudo-sites available on immediate sequence context downstream of the activated one. In addition, 5' pseudo-sites with an increased complementarity to U1snRNA up to 91% do not compete with the identified scanning mechanism. Altogether, these findings, which unveil a cell type-independent 5'-3'-oriented scanning process for accurate recognition of the authentic 5' splice site, reconciliate apparently contradictory observations by establishing a hierarchy of competitiveness among the determinants involved in 5' splice site selection.

  5. Science, conservation, and camera traps (United States)

    Nichols, James D.; Karanth, K. Ullas; O'Connel, Allan F.; O'Connell, Allan F.; Nichols, James D.; Karanth, K. Ullas


    Biologists commonly perceive camera traps as a new tool that enables them to enter the hitherto secret world of wild animals. Camera traps are being used in a wide range of studies dealing with animal ecology, behavior, and conservation. Our intention in this volume is not to simply present the various uses of camera traps, but to focus on their use in the conduct of science and conservation. In this chapter, we provide an overview of these two broad classes of endeavor and sketch the manner in which camera traps are likely to be able to contribute to them. Our main point here is that neither photographs of individual animals, nor detection history data, nor parameter estimates generated from detection histories are the ultimate objective of a camera trap study directed at either science or management. Instead, the ultimate objectives are best viewed as either gaining an understanding of how ecological systems work (science) or trying to make wise decisions that move systems from less desirable to more desirable states (conservation, management). Therefore, we briefly describe here basic approaches to science and management, emphasizing the role of field data and associated analyses in these processes. We provide examples of ways in which camera trap data can inform science and management.

  6. Model checking the HAVi leader election protocol

    NARCIS (Netherlands)

    J.M.T. Romijn (Judi)


    textabstractThe HAVi specification proposes an architecture for audio/video interoperability in home networks. Part of the HAVi specification is a distributed leader election protocol. We have modelled this leader election protocol in Promela and Lotos and have checked several properties with the

  7. Political leader survival : does competence matter?

    NARCIS (Netherlands)

    Yu, Shu; Jong-A-Pin, Richard

    We examine whether economic and military competence of political leaders affect their duration in office. We introduce leader heterogeneity in the selectorate theory of Bueno de Mesquita et al. (2003) and derive the hypothesis that in the presence of a revolutionary threat, economic competence is

  8. Developing Adaptive Leaders, A Cultural Imperative

    National Research Council Canada - National Science Library

    Mulbury, Douglas S


    .... The paper then analyzes current research into the nature of adaptive performance and how to develop it in others. It concludes by examining organizational and cultural factors that affect adaptive performance. Throughout recommendations are offered for how the Army should alter its leader development program to better prepare adaptive leaders.

  9. Practical Leader Development Program Using Emotional Intelligence

    DEFF Research Database (Denmark)

    Barfod, Jakob Rømer; Bakkegaard, Bjarne


    The Danish Army has more than ten years of experience working with developing emotional intelligence in the Royal Danish Army Officers’ Academy (RDAOA), and the Academy has developed military leaders who have benefitted from emotional intelligence training. Today many of the military leaders...

  10. District Leaders' Framing of Educator Evaluation Policy (United States)

    Woulfin, Sarah L.; Donaldson, Morgaen L.; Gonzales, Richard


    Purpose: Educator evaluation systems have recently undergone scrutiny and reform, and district and school leaders play a key role in interpreting and enacting these systems. This article uses framing theory to understand district leaders' interpretation and advancement of a state's new educator evaluation policy. Research Methods: The article…

  11. The Called, Chosen, and Faithful Leader (United States)

    Davis, Hartwell T. Paul


    Leaders are made, not born. Like so many other of life's complex issues, the question of nature vs. nurture in leadership is one that is analyzed, researched, and debated by educators, philosophers, social scientist, and even leaders themselves. Leadership has been dissected as to personality, character, and behavior. Researchers have developed…

  12. Environmental leaders and pioneers: agents of change?

    NARCIS (Netherlands)

    Liefferink, J.D.; Wurzel, R.K.W.


    This article distinguishes between states acting as environmental leaders or pioneers. While leaders usually actively seek to attract followers, this is not normally the case for pioneers. Dependent on their internal and external ambitions, states may take on the position of a laggard, pioneer,

  13. Characteristics Related to Female & Male Leaders (United States)

    Richardson, Agnes M.


    The following research investigated gender and the leadership role and determined if there are differences in leadership styles, behaviors, traits, and characteristics between female leaders and male leaders. Literature suggests there are specific gender leadership differences between males and females in leadership styles, behaviors, traits, and…

  14. Educators as Serving Leaders in the Classroom and on Campus (United States)

    Bowman, Richard


    Counterintuitively, the more one develops as a leader, the less of a leader one becomes. What do great leaders do? Great leaders are ambitious first and foremost for the cause, the mission, the work--not themselves. Educators as "serving leaders" sense that every action they take, together with every decision that they make, either…

  15. What about the leader? Crossover of emotional exhaustion and work engagement from followers to leaders. (United States)

    Wirtz, Nina; Rigotti, Thomas; Otto, Kathleen; Loeb, Carina


    Although a growing body of research links leadership behavior to follower health, comparatively little is known about the health effects of being in the lead. This longitudinal study of 315 team members and 67 leaders examined the crossover of emotional exhaustion and work engagement from followers to leaders. Leader emotional self-efficacy was tested as a moderator in the crossover process. Multiple regression analyses revealed that followers' work engagement was positively related to leaders' work engagement eight months later, controlling for followers' tenure with the leader, leader gender, autonomy, workload, and work engagement at Time 1. Leaders' emotional self-efficacy did not moderate the crossover of work engagement. Followers' emotional exhaustion was not directly related to leaders' emotional exhaustion over time. We did find a significant interaction effect for follower emotional exhaustion and leader emotional self-efficacy. This study is the first to show that crossover of emotional exhaustion and work engagement can unfold over time from team members to leaders. Main theoretical implications lie in the finding that-in line with job demands-resources theory-followers' psychological states can pose a demand or resource for leaders, and influence their well-being. For practitioners, our results offer valuable insights regarding the design of organizational health interventions as well as leadership development measures. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  16. Show and tell: how supervisors facilitate leader development among transitioning leaders. (United States)

    Dragoni, Lisa; Park, Haeseen; Soltis, Jim; Forte-Trammell, Sheila


    We argue that studying leaders experiencing a job transition offers a unique opportunity to explore initial changes in leaders' development in their cognition and action. Here, we examine 2 early indicators of leaders' development-their acquisition of knowledge regarding their new role (a cognitive outcome) and the time they allocate toward leading others (a behavioral outcome)-and how supervisors can facilitate these forms of development among transitioning leaders. With a sample of 110 first-line leaders who we tracked over approximately 10 months at 4 different points in time, we tested the efficacy of supervisors' support in the form of modeling effective leadership behavior (i.e., "show") and the provision of job information (i.e., "tell"). Results from random coefficient modeling revealed that the interactive effect of supervisors' "show" and "tell" accelerates the rate of transitioning leaders' self-perceived role knowledge acquisition over time. This upward trajectory is even more pronounced for transitioning leaders who have not been exposed to an exceptional leader during their careers. Further, with a lagged design, we found that leaders who report greater role knowledge allocate more time toward leading others, thus indicating initial changes in these leaders' behavior. We discuss these findings in light of their theoretical and practical importance to the field of leader development. PsycINFO Database Record (c) 2014 APA, all rights reserved

  17. Leader power and leader self-serving behavior : The role of effective leadership beliefs and performance information

    NARCIS (Netherlands)

    Rus, Diana; van Knippenberg, Daan; Wisse, Barbara


    In this research we investigated the role played by leader power in determining leader self-serving behavior. Based on an integration of insights from research on the determinants of leader behavior and the power-approach theory, we hypothesized that with higher leader power leader self-serving

  18. Interplay between estrogen receptor and AKT in estradiol-induced alternative splicing. (United States)

    Bhat-Nakshatri, Poornima; Song, Eun-Kyung; Collins, Nikail R; Uversky, Vladimir N; Dunker, A Keith; O'Malley, Bert W; Geistlinger, Tim R; Carroll, Jason S; Brown, Myles; Nakshatri, Harikrishna


    Alternative splicing is critical for generating complex proteomes in response to extracellular signals. Nuclear receptors including estrogen receptor alpha (ERα) and their ligands promote alternative splicing. The endogenous targets of ERα:estradiol (E2)-mediated alternative splicing and the influence of extracellular kinases that phosphorylate ERα on E2-induced splicing are unknown. MCF-7 and its anti-estrogen derivatives were used for the majority of the assays. CD44 mini gene was used to measure the effect of E2 and AKT on alternative splicing. ExonHit array analysis was performed to identify E2 and AKT-regulated endogenous alternatively spliced apoptosis-related genes. Quantitative reverse transcription polymerase chain reaction was performed to verify alternative splicing. ERα binding to alternatively spliced genes was verified by chromatin immunoprecipitation assay. Bromodeoxyuridine incorporation-ELISA and Annexin V labeling assays were done to measure cell proliferation and apoptosis, respectively. We identified the targets of E2-induced alternative splicing and deconstructed some of the mechanisms surrounding E2-induced splicing by combining splice array with ERα cistrome and gene expression array. E2-induced alternatively spliced genes fall into at least two subgroups: coupled to E2-regulated transcription and ERα binding to the gene without an effect on rate of transcription. Further, AKT, which phosphorylates both ERα and splicing factors, influenced ERα:E2 dependent splicing in a gene-specific manner. Genes that are alternatively spliced include FAS/CD95, FGFR2, and AXIN-1. E2 increased the expression of FGFR2 C1 isoform but reduced C3 isoform at mRNA level. E2-induced alternative splicing of FAS and FGFR2 in MCF-7 cells correlated with resistance to FAS activation-induced apoptosis and response to keratinocyte growth factor (KGF), respectively. Resistance of MCF-7 breast cancer cells to the anti-estrogen tamoxifen was associated with ER

  19. RET: a poly A-trap retrovirus vector for reversible disruption and expression monitoring of genes in living cells. (United States)

    Ishida, Y; Leder, P


    Gene trapping is a form of insertional mutagenesis that causes disruption of gene function. Here we report the construction and extensive examination of a versatile retrovirus vector, RET (removable exon trap). The RET vector uses an improved poly A-trap strategy for the efficient identification of functional genes regardless of their expression status in target cells. A combination of a potentially very strong splice acceptor and an effective polyadenylation signal assures the complete disruption of the function of trapped genes. Inclusion of a promoterless GFP cDNA in the RET vector allows the expression pattern of the trapped gene to be easily monitored in living cells. Finally, because of loxP-containing LTRs at both ends, the integrated proviruses can be removed from the genome of infected cells by Cre-mediated homologous recombination. Hence, it is possible to attribute the mutant phenotype of gene-trapped cells directly to RET integration by inducing phenotypic reversion after provirus excision. The RET system can be used in conjunction with cell lines with functional heterozygosity, embryonic stem cells, lineage-committed cell lines that differentiate in response to specific inducing factors and other responsive cell lines that can be selected by virtue of their induced green fluorescence protein expression. PMID:10572187

  20. Identification of a Residue (Glu60) in TRAP Required for Inducing Efficient Transcription Termination at thetrpAttenuator Independent of Binding Tryptophan and RNA. (United States)

    McAdams, Natalie M; Patterson, Andrea; Gollnick, Paul


    Transcription of the tryptophan ( trp ) operon in Bacillus subtilis is regulated by an attenuation mechanism. Attenuation is controlled by the t rp R NA-binding a ttenuation p rotein (TRAP). TRAP binds to a site in the 5' leader region of the nascent trp transcript in response to the presence of excess intracellular tryptophan. This binding induces transcription termination upstream of the structural genes of the operon. In prior attenuation models, the role of TRAP was only to alter the secondary structure of the leader region RNA so as to promote formation of the trp attenuator, which was presumed to function as an intrinsic terminator. However, formation of the attenuator alone has been shown to be insufficient to induce efficient termination, indicating that TRAP plays an additional role in this process. To further examine the function of TRAP, we performed a genetic selection for mutant TRAPs that bind tryptophan and RNA but show diminished termination at the trp attenuator. Five such TRAP mutants were obtained. Four of these have substitutions at Glu60, three of which are Lys (E60K) substitutions and the fourth of which is a Val (E60V) substitution. The fifth mutant obtained contains a substitution at Ile63, which is on the same β-strand of TRAP as Glu60. Purified E60K TRAP binds tryptophan and RNA with properties similar to those of the wild type but is defective at inducing termination at the trp attenuator in vitro IMPORTANCE Prior models for attenuation control of the B. subtilis trp operon suggested that the only role for TRAP is to bind to the leader region RNA and alter its folding to induce formation of an intrinsic terminator. However, several recent studies suggested that TRAP plays an additional role in the termination mechanism. We hypothesized that this function could involve residues in TRAP other than those required to bind tryptophan and RNA. Here we obtained TRAP mutants with alterations at Glu60 that are deficient at inducing termination in

  1. A magnetic particle micro-trap for large trapping surfaces

    KAUST Repository

    Gooneratne, Chinthaka P.


    Manipulation of micron-size magnetic particles of the superparamagnetic type contributes significantly in many applications like controlling the antibody/antigen binding process in immunoassays. Specifically, more target biomolecules can be attached/tagged and analyzed since the three dimensional structure of the magnetic particles increases the surface to volume ratio. Additionally, such biomolecular-tagged magnetic particles can be easily manipulated by an external magnetic field due to their superparamagnetic behavior. Therefore, magnetic particle- based immunoassays are extensively applied in micro-flow cytometry. The design of a square-loop micro-trap as a magnetic particle manipulator as well as numerical and experimental analysis is presented. Experimental results showed that the micro-trap could successfully trap and concentrate magnetic particles from a large to a small area with a high spatial range.

  2. RRM domain of Arabidopsis splicing factor SF1 is important for pre-mRNA splicing of a specific set of genes

    KAUST Repository

    Lee, Keh Chien


    The RNA recognition motif of Arabidopsis splicing factor SF1 affects the alternative splicing of FLOWERING LOCUS M pre-mRNA and a heat shock transcription factor HsfA2 pre-mRNA. Splicing factor 1 (SF1) plays a crucial role in 3\\' splice site recognition by binding directly to the intron branch point. Although plant SF1 proteins possess an RNA recognition motif (RRM) domain that is absent in its fungal and metazoan counterparts, the role of the RRM domain in SF1 function has not been characterized. Here, we show that the RRM domain differentially affects the full function of the Arabidopsis thaliana AtSF1 protein under different experimental conditions. For example, the deletion of RRM domain influences AtSF1-mediated control of flowering time, but not the abscisic acid sensitivity response during seed germination. The alternative splicing of FLOWERING LOCUS M (FLM) pre-mRNA is involved in flowering time control. We found that the RRM domain of AtSF1 protein alters the production of alternatively spliced FLM-β transcripts. We also found that the RRM domain affects the alternative splicing of a heat shock transcription factor HsfA2 pre-mRNA, thereby mediating the heat stress response. Taken together, our results suggest the importance of RRM domain for AtSF1-mediated alternative splicing of a subset of genes involved in the regulation of flowering and adaptation to heat stress.

  3. Features generated for computational splice-site prediction correspond to functional elements

    Directory of Open Access Journals (Sweden)

    Wilbur W John


    Full Text Available Abstract Background Accurate selection of splice sites during the splicing of precursors to messenger RNA requires both relatively well-characterized signals at the splice sites and auxiliary signals in the adjacent exons and introns. We previously described a feature generation algorithm (FGA that is capable of achieving high classification accuracy on human 3' splice sites. In this paper, we extend the splice-site prediction to 5' splice sites and explore the generated features for biologically meaningful splicing signals. Results We present examples from the observed features that correspond to known signals, both core signals (including the branch site and pyrimidine tract and auxiliary signals (including GGG triplets and exon splicing enhancers. We present evidence that features identified by FGA include splicing signals not found by other methods. Conclusion Our generated features capture known biological signals in the expected sequence interval flanking splice sites. The method can be easily applied to other species and to similar classification problems, such as tissue-specific regulatory elements, polyadenylation sites, promoters, etc.

  4. The Role of Canonical and Noncanonical Pre-mRNA Splicing in Plant Stress Responses

    Directory of Open Access Journals (Sweden)

    A. S. Dubrovina


    Full Text Available Plants are sessile organisms capable of adapting to various environmental constraints, such as high or low temperatures, drought, soil salinity, or pathogen attack. To survive the unfavorable conditions, plants actively employ pre-mRNA splicing as a mechanism to regulate expression of stress-responsive genes and reprogram intracellular regulatory networks. There is a growing evidence that various stresses strongly affect the frequency and diversity of alternative splicing events in the stress-responsive genes and lead to an increased accumulation of mRNAs containing premature stop codons, which in turn have an impact on plant stress response. A number of studies revealed that some mRNAs involved in plant stress response are spliced counter to the traditional conception of alternative splicing. Such noncanonical mRNA splicing events include trans-splicing, intraexonic deletions, or variations affecting multiple exons and often require short direct repeats to occur. The noncanonical alternative splicing, along with common splicing events, targets the spliced transcripts to degradation through nonsense-mediated mRNA decay or leads to translation of truncated proteins. Investigation of the diversity, biological consequences, and mechanisms of the canonical and noncanonical alternative splicing events will help one to identify those transcripts which are promising for using in genetic engineering and selection of stress-tolerant plants.

  5. Leadership Makes a Difference Growing Federal Civilian Leaders

    National Research Council Canada - National Science Library

    Muellerweiss, Alice


    The quality of federal leaders is vital to the effectiveness of our government. No longer can we depend on leaders simply and conveniently emerging, rather we must invest in a deliberate systematic process to develop leaders at all levels...

  6. Affective match: Leader emotions, follower positive affect, and follower performance

    NARCIS (Netherlands)

    Damen, F.; van Knippenberg, B.M.; van Knippenberg, D.


    Leader emotions may play an important role in leadership effectiveness. Extending earlier research on leader emotional displays and leadership effectiveness, we propose that the affective match between follower positive affect (PA) and leaders' emotional displays moderates the effectiveness of

  7. A Feature-Based Forensic Procedure for Splicing Forgeries Detection

    Directory of Open Access Journals (Sweden)

    Irene Amerini


    Full Text Available Nowadays, determining if an image appeared somewhere on the web or in a magazine or is authentic or not has become crucial. Image forensics methods based on features have demonstrated so far to be very effective in detecting forgeries in which a portion of an image is cloned somewhere else onto the same image. Anyway such techniques cannot be adopted to deal with splicing attack, that is, when the image portion comes from another picture that then, usually, is not available anymore for an operation of feature match. In this paper, a procedure in which these techniques could also be employed will be shown to get rid of splicing attack by resorting to the use of some repositories of images available on the Internet like Google Images or TinEye Reverse Image Search. Experimental results are presented on some real case images retrieved on the Internet to demonstrate the capacity of the proposed procedure.

  8. Understanding health policy leaders' training needs.

    Directory of Open Access Journals (Sweden)

    Carey Roth Bayer

    Full Text Available We assessed the training needs of health policy leaders and practitioners across career stages; identified areas of core content for health policy training programs; and, identified training modalities for health policy leaders.We convened a focus group of health policy leaders at varying career stages to inform the development of the Health Policy Leaders' Training Needs Assessment tool. We piloted and distributed the tool electronically. We used descriptive statistics and thematic coding for analysis.Seventy participants varying in age and stage of career completed the tool. "Cost implications of health policies" ranked highest for personal knowledge development and "intersection of policy and politics" ranked highest for health policy leaders in general. "Effective communication skills" ranked as the highest skill element and "integrity" as the highest attribute element. Format for training varied based on age and career stage.This study highlighted the training needs of health policy leaders personally as well as their perceptions of the needs for training health policy leaders in general. The findings are applicable for current health policy leadership training programs as well as those in development.

  9. Factors supporting dentist leaders' retention in leadership. (United States)

    Tuononen, T; Lammintakanen, J; Suominen, A L


    The aim was to study factors associated with staying in a dentist leadership position. We used an electronic questionnaire to gather data from 156 current or former Finnish dentist leaders in 2014. Principal component analysis categorized statements regarding time usage and opportunities in managerial work into five main components. Associations between these main component scores and the tendency to stay as a leader were analyzed with logistic regression. Out of the five main components, two were significantly associated with staying as a leader: 'career intentions', which represented intent to continue or to leave the leadership position; and 'work time control opportunities', which represented how leaders could control their own work time. Other factors that supported staying were leadership education, more work time available for leadership work, and lower age. The main component 'work pressure' decreased, although not significantly, the odds of continuing; it included lack of leadership work time, and pressure from superiors or subordinates. Leaders have important roles in health care, ensuring everyday operations as well as developing their organizations to meet future challenges. Knowledge of these supporting factors will enable dentist leaders and their organizations to improve working conditions in order to recruit and retain motivated and competent persons. In addition, well-designed education is important to inspire and encourage future leaders. Copyright© 2017 Dennis Barber Ltd.

  10. Alternative splice variants of the human PD-1 gene

    DEFF Research Database (Denmark)

    Nielsen, Christian; Ohm-Laursen, Line; Barington, Torben


    PD-1 is an immunoregulatory receptor expressed on the surface of activated T cells, B cells, and monocytes. We describe four alternatively spliced PD-1 mRNA transcripts (PD-1Deltaex2, PD-1Deltaex3, PD-1Deltaex2,3, and PD-1Deltaex2,3,4) in addition to the full length isoform. PD-1Deltaex2 and PD-1...

  11. Exon expression and alternatively spliced genes in Tourette Syndrome. (United States)

    Tian, Yingfang; Liao, Isaac H; Zhan, Xinhua; Gunther, Joan R; Ander, Bradley P; Liu, Dazhi; Lit, Lisa; Jickling, Glen C; Corbett, Blythe A; Bos-Veneman, Netty G P; Hoekstra, Pieter J; Sharp, Frank R


    Tourette Syndrome (TS) is diagnosed based upon clinical criteria including motor and vocal tics. We hypothesized that differences in exon expression and splicing might be useful for pathophysiology and diagnosis. To demonstrate exon expression and alternatively spliced gene differences in blood of individuals with TS compared to healthy controls (HC), RNA was isolated from the blood of 26 un-medicated TS subjects and 23 HC. Each sample was run on Affymetrix Human Exon 1.0 ST (HuExon) arrays and on 3' biased U133 Plus 2.0 (HuU133) arrays. To investigate the differentially expressed exons and transcripts, analyses of covariance (ANCOVA) were performed, controlling for age, gender, and batch. Differential alternative splicing patterns between TS and HC were identified using analyses of variance (ANOVA) models in Partek. Three hundred and seventy-six exon probe sets were differentially expressed between TS and HC (raw P |1.2|) that separated TS and HC subjects using hierarchical clustering and Principal Components Analysis. The probe sets predicted TS compared to HC with a >90% sensitivity and specificity using a 10-fold cross-validation. Ninety genes (transcripts) had differential expression of a single exon (raw P < 0.005) and were predicted to be alternatively spliced (raw P < 0.05) in TS compared to HC. These preliminary findings might provide insight into the pathophysiology of TS and potentially provide prognostic and diagnostic biomarkers. However, the findings are tempered by the small sample size and multiple comparisons and require confirmation using PCR or deep RNA sequencing and a much larger patient population. Copyright © 2010 Wiley-Liss, Inc.

  12. The plethora of PMCA isoforms: Alternative splicing and differential expression. (United States)

    Krebs, Joachim


    In this review the four different genes of the mammalian plasma membrane calcium ATPase (PMCA) and their spliced isoforms are discussed with respect to their tissue distribution, their differences during development and their importance for regulating Ca²⁺ homeostasis under different conditions. This article is part of a Special Issue entitled: 13th European Symposium on Calcium. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Conserved and species-specific alternative splicing in mammalian genomes

    Directory of Open Access Journals (Sweden)

    Favorov Alexander V


    Full Text Available Abstract Background Alternative splicing has been shown to be one of the major evolutionary mechanisms for protein diversification and proteome expansion, since a considerable fraction of alternative splicing events appears to be species- or lineage-specific. However, most studies were restricted to the analysis of cassette exons in pairs of genomes and did not analyze functionality of the alternative variants. Results We analyzed conservation of human alternative splice sites and cassette exons in the mouse and dog genomes. Alternative exons, especially minor-isofom ones, were shown to be less conserved than constitutive exons. Frame-shifting alternatives in the protein-coding regions are less conserved than frame-preserving ones. Similarly, the conservation of alternative sites is highest for evenly used alternatives, and higher when the distance between the sites is divisible by three. The rate of alternative-exon and site loss in mouse is slightly higher than in dog, consistent with faster evolution of the former. The evolutionary dynamics of alternative sites was shown to be consistent with the model of random activation of cryptic sites. Conclusion Consistent with other studies, our results show that minor cassette exons are less conserved than major-alternative and constitutive exons. However, our study provides evidence that this is caused not only by exon birth, but also lineage-specific loss of alternative exons and sites, and it depends on exon functionality.

  14. Alternative Splicing of G9a Regulates Neuronal Differentiation

    Directory of Open Access Journals (Sweden)

    Ana Fiszbein


    Full Text Available Chromatin modifications are critical for the establishment and maintenance of differentiation programs. G9a, the enzyme responsible for histone H3 lysine 9 dimethylation in mammalian euchromatin, exists as two isoforms with differential inclusion of exon 10 (E10 through alternative splicing. We find that the G9a methyltransferase is required for differentiation of the mouse neuronal cell line N2a and that E10 inclusion increases during neuronal differentiation of cultured cells, as well as in the developing mouse brain. Although E10 inclusion greatly stimulates overall H3K9me2 levels, it does not affect G9a catalytic activity. Instead, E10 increases G9a nuclear localization. We show that the G9a E10+ isoform is necessary for neuron differentiation and regulates the alternative splicing pattern of its own pre-mRNA, enhancing E10 inclusion. Overall, our findings indicate that by regulating its own alternative splicing, G9a promotes neuron differentiation and creates a positive feedback loop that reinforces cellular commitment to differentiation.

  15. VEGF Spliced Variants: Possible Role of Anti-Angiogenesis Therapy

    Directory of Open Access Journals (Sweden)

    Caroline Hilmi


    Full Text Available Angiogenesis has been targeted in retinopathies, psoriasis, and a variety of cancers (colon, breast, lung, and kidney. Among these tumour types, clear cell renal cell carcinomas (RCCs are the most vascularized tumours due to mutations of the von Hippel Lindau gene resulting in HIF-1 alpha stabilisation and overexpression of Vascular Endothelial Growth Factor (VEGF. Surgical nephrectomy remains the most efficient curative treatment for patients with noninvasive disease, while VEGF targeting has resulted in varying degrees of success for treating metastatic disease. VEGF pre-mRNA undergoes alternative splicing generating pro-angiogenic isoforms. However, the recent identification of novel splice variants of VEGF with anti-angiogenic properties has provided some insight for the lack of current treatment efficacy. Here we discuss an explanation for the relapse to anti-angiogenesis treatment as being due to either an initial or acquired resistance to the therapy. We also discuss targeting angiogenesis via SR (serine/arginine-rich proteins implicated in VEGF splicing.

  16. Diverse splicing patterns of exonized Alu elements in human tissues.

    Directory of Open Access Journals (Sweden)

    Lan Lin


    Full Text Available Exonization of Alu elements is a major mechanism for birth of new exons in primate genomes. Prior analyses of expressed sequence tags show that almost all Alu-derived exons are alternatively spliced, and the vast majority of these exons have low transcript inclusion levels. In this work, we provide genomic and experimental evidence for diverse splicing patterns of exonized Alu elements in human tissues. Using Exon array data of 330 Alu-derived exons in 11 human tissues and detailed RT-PCR analyses of 38 exons, we show that some Alu-derived exons are constitutively spliced in a broad range of human tissues, and some display strong tissue-specific switch in their transcript inclusion levels. Most of such exons are derived from ancient Alu elements in the genome. In SEPN1, mutations of which are linked to a form of congenital muscular dystrophy, the muscle-specific inclusion of an Alu-derived exon may be important for regulating SEPN1 activity in muscle. Realtime qPCR analysis of this SEPN1 exon in macaque and chimpanzee tissues indicates human-specific increase in its transcript inclusion level and muscle specificity after the divergence of humans and chimpanzees. Our results imply that some Alu exonization events may have acquired adaptive benefits during the evolution of primate transcriptomes.

  17. Changes in RNA Splicing in Developing Soybean (Glycine max Embryos

    Directory of Open Access Journals (Sweden)

    Delasa Aghamirzaie


    Full Text Available Developing soybean seeds accumulate oils, proteins, and carbohydrates that are used as oxidizable substrates providing metabolic precursors and energy during seed germination. The accumulation of these storage compounds in developing seeds is highly regulated at multiple levels, including at transcriptional and post-transcriptional regulation. RNA sequencing was used to provide comprehensive information about transcriptional and post-transcriptional events that take place in developing soybean embryos. Bioinformatics analyses lead to the identification of different classes of alternatively spliced isoforms and corresponding changes in their levels on a global scale during soybean embryo development. Alternative splicing was associated with transcripts involved in various metabolic and developmental processes, including central carbon and nitrogen metabolism, induction of maturation and dormancy, and splicing itself. Detailed examination of selected RNA isoforms revealed alterations in individual domains that could result in changes in subcellular localization of the resulting proteins, protein-protein and enzyme-substrate interactions, and regulation of protein activities. Different isoforms may play an important role in regulating developmental and metabolic processes occurring at different stages in developing oilseed embryos.

  18. The Decision Calculus of Terrorist Leaders

    Directory of Open Access Journals (Sweden)

    J. Tyson Chatagnier


    Full Text Available This article contributes to the literature on terrorist group decision-making by introducing a new procedure, Applied Decision Analysis, in an attempt to understand how leaders of terrorist organizations make decisions. We examine twenty-three decisions taken by leaders of three terrorist organizations: Al-Qaeda, Hamas, and Hizballah. We also demonstrate the use of the Applied Decision Analysis procedure to uncover the "Decision DNA" or “decision code” of leaders of such organizations. After reviewing the results and insights derived from this analysis, we conclude with implications for policies to counter terrorism.

  19. Saddam Hussein: Portrait of an Arab Leader (United States)


    AD-A240 117 SADDAM HUSSEIN . PORTRAIT OF AN ARAB LEADER A thesis presented to the Faculty of the U.S. Army Command and General Staff College in...Hussein: Protrait of an Arab Leader 6. AUTHOR(S) Maj Ray T. Bradley, USAF 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION...89) j.] SADDAM HUSSEIN PORTRAIT OF AN ARAB LEADER A thesis presented to the Faculty of the U.S. Army Command and GenprIl qtaff College in parti.i

  20. Internationalization in schools - perspectives of school leaders

    DEFF Research Database (Denmark)

    Egekvist, Ulla Egidiussen; Lyngdorf, Niels Erik; Du, Xiangyun


    This paper explores how internationalization ideas in primary and lower secondary schools can be developed through the acquisition of international experience abroad by leaders. The study was inspired by existing literature on internationalization and leadership, and theories of experiential...... learning and reflection. Empirically, qualitative material was derived from a study of nineteen Danish school leaders participating in an eight-day delegation visit to China. This study shows that international experience for leaders can be used to develop ideas for internationalization at the school level...

  1. Neutral atom traps of radioactives

    International Nuclear Information System (INIS)

    Behr, J.A.


    Neutral atoms trapped with modern laser cooling techniques offer the promise of improving several broad classes of experiments with radioactive isotopes. In nuclear β decay, neutrino spectroscopy from beta-recoil coincidences, along with highly polarized samples, enable experiments to search for non-Standard Model interactions, test whether parity symmetry is maximally violated, and search for new sources of time reversal violation. Ongoing efforts at TRIUMF, Los Alamos and Berkeley will be highlighted. The traps also offer bright sources for Doppler-free spectroscopy, particularly in high-Z atoms where precision measurements could measure the strength of weak neutral nucleon-nucleon and electron-nucleon interactions. Physics with francium atoms has been vigorously pursued at Stony Brook. Several facilities plan work with radioactive atom traps; concrete plans and efforts at KVI Groningen and Legnaro will be among those summarized. Contributions to the multidisciplinary field of trace analysis will be left up to other presenters

  2. Neutral atom traps of radioactives

    CERN Document Server

    Behr, J A


    Neutral atoms trapped with modern laser cooling techniques offer the promise of improving several broad classes of experiments with radioactive isotopes. In nuclear beta decay, neutrino spectroscopy from beta-recoil coincidences, along with highly polarized samples, enable experiments to search for non-Standard Model interactions, test whether parity symmetry is maximally violated, and search for new sources of time reversal violation. Ongoing efforts at TRIUMF, Los Alamos and Berkeley will be highlighted. The traps also offer bright sources for Doppler-free spectroscopy, particularly in high-Z atoms where precision measurements could measure the strength of weak neutral nucleon-nucleon and electron-nucleon interactions. Physics with francium atoms has been vigorously pursued at Stony Brook. Several facilities plan work with radioactive atom traps; concrete plans and efforts at KVI Groningen and Legnaro will be among those summarized. Contributions to the multidisciplinary field of trace analysis will be left...

  3. High-spin nuclear traps

    International Nuclear Information System (INIS)

    Walker, P.; Dracoulis, G.


    The reaction pathways in stars, where all the heavy elements in the Universe were formed, are inextricably linked with isomers that live long enough to capture a neutron or proton before they decay. These isomers usually have excitation energies below 0.1 MeV. It is also possible to find highly excited isomers, with several MeV of excitation energy, that are trapped because of their large angular momentum (or spin). But attempts to understand the long-lived highly excited isomers, sometimes known as ''spin traps'', have been hampered by the difficulty of producing this exotic form of nuclear matter. Now, a new generation of radioactive ion beams promises a revolution in the study of high-spin nuclear traps. (author)

  4. Laser traps for radioactive isotopes

    International Nuclear Information System (INIS)

    Voytas, P.A.; Behr, J.A.; Ghosh, A.; Gwinner, G.; Orozco, L.A.; Simsarian, J.E.; Sprouse, G.D.; Xu, F.


    The techniques of laser cooling and trapping now make it possible to observe large samples of stable atoms in a small volume at low temperature. This capability was recently extended to radioactive isotopes. This opens up new opportunities for the investigation of fundamental symmetries through measurements using radioactive atoms. In this paper we will discuss several fundamental measurements in atomic systems and how the ability to trap radioactive atoms will play an important role in improving the precision of such measurements. Measurements of the effects of the weak interaction are of particular note since they are becoming quite precise. In particular, we will describe in detail the system developed at Stony Brook to trap radioactive alkali atoms and measure weak interaction effects in francium isotopes. (orig.)

  5. Establishing the next generation at work: leader generativity as a moderator of the relationships between leader age, leader-member exchange, and leadership success. (United States)

    Zacher, Hannes; Rosing, Kathrin; Henning, Thomas; Frese, Michael


    In this study, the authors investigated leader generativity as a moderator of the relationships between leader age, leader-member exchange, and three criteria of leadership success (follower perceptions of leader effectiveness, follower satisfaction with leader, and follower extra effort). Data came from 128 university professors paired with one research assistant each. Results showed positive relationships between leader age and leader generativity, and negative relationships between leader age and follower perceptions of leader effectiveness and follower extra effort. Consistent with expectations based on leadership categorization theory, leader generativity moderated the relationships between leader age and all three criteria of leadership success, such that leaders high in generativity were better able to maintain high levels of leadership success at higher ages than leaders low in generativity. Finally, results of mediated moderation analyses showed that leader-member exchange quality mediated these moderating effects. The findings suggest that, in combination, leader age and the age-related construct of generativity importantly influence leadership processes and outcomes. (c) 2011 APA, all rights reserved.

  6. Sound trapping and dredging barriers. (United States)

    Wang, Xu; Wang, Xiaonan; Yu, Wuzhou; Jiang, Zaixiu; Mao, Dongxing


    When sound barriers are installed on both sides of a noise source, degradation in performance is observed. Barriers having negative-phase-gradient surfaces successfully eliminate this drawback by trapping sound energy in between the barriers. In contrast, barriers can also be designed to "dredge" the energy flux out. An extended model considering higher-order diffractions, which resulted from the interplay of the induced surface wave and barrier surface periodicity, is presented. It is found that the sound dredging barriers provide a remarkable enhancement over the trapping ones, and hence have the potential to be widely used in noise control engineering.

  7. A live-trap and trapping technique for fossorial mammals

    African Journals Online (AJOL)

    comer of the door and prevents reopening by sliding into the slit at the top of the door. A hole is drilled through the back of the door housing unit and the door to accommodate an L-shaped wire (bent bicycle spoke) measuring 185 mm along the top of the trap, and a 60 mm portion which extends down into the interior.

  8. Analysis and recognition of 5 ' UTR intron splice sites in human pre-mRNA

    DEFF Research Database (Denmark)

    Eden, E.; Brunak, Søren


    Prediction of splice sites in non-coding regions of genes is one of the most challenging aspects of gene structure recognition. We perform a rigorous analysis of such splice sites embedded in human 5' untranslated regions (UTRs), and investigate correlations between this class of splice sites...... and other features found in the adjacent exons and introns. By restricting the training of neural network algorithms to 'pure' UTRs (not extending partially into protein coding regions), we for the first time investigate the predictive power of the splicing signal proper, in contrast to conventional splice...... in the synaptic weights of the neural networks trained to identify UTR donor sites. Conventional splice site prediction methods perform poorly in UTRs because the reading frame pattern is absent. The NetUTR method presented here performs 2-.3-fold better compared with NetGene2 and GenScan in 5' UTRs. We also...

  9. Characterization of TTN Novex Splicing Variants across Species and the Role of RBM20 in Novex-Specific Exon Splicing

    Directory of Open Access Journals (Sweden)

    Zhilong Chen


    Full Text Available Titin (TTN is a major disease-causing gene in cardiac muscle. Titin (TTN contains 363 exons in human encoding various sizes of TTN protein due to alternative splicing regulated mainly by RNA binding motif 20 (RBM20. Three isoforms of TTN protein are produced by mutually exclusive exons 45 (Novex 1, 46 (Novex 2, and 48 (Novex 3. Alternatively splicing in Novex isoforms across species and whether Novex isoforms are associated with heart disease remains completely unknown. Cross-species exon comparison with the mVISTA online tool revealed that exon 45 is more highly conserved across all species than exons 46 and 48. Importantly, a conserved region between exons 47 and 48 across species was revealed for the first time. Reverse transcript polymerase chain reaction (RT-PCR and DNA sequencing confirmed a new exon named as 48′ in Novex 3. In addition, with primer pairs for Novex 1, a new truncated form preserving introns 44 and 45 was discovered. We discovered that Novex 2 is not expressed in the pig, mouse, and rat with Novex 2 primer pairs. Unexpectedly, three truncated forms were identified. One TTN variant with intron 46 retention is mainly expressed in the human and frog heart, another variant with co-expression of exons 45 and 46 exists predominantly in chicken and frog heart, and a third with retention of introns 45 and 46 is mainly expressed in pig, mouse, rat, and chicken. Using Rbm20 knockout rat heart, we revealed that RBM20 is not a splicing regulator of Novex variants. Furthermore, the expression levels of Novex variants in human hearts with cardiomyopathies suggested that Novexes 2 and 3 could be associated with dilated cardiomyopathy (DCM and/or arrhythmogenic right ventricular cardiomyopathy (ARVC. Taken together, our study reveals that splicing diversity of Novex exons across species and Novex variants might play a role in cardiomyopathy.

  10. Ion trap architectures and new directions (United States)

    Siverns, James D.; Quraishi, Qudsia


    Trapped ion technology has seen advances in performance, robustness and versatility over the last decade. With increasing numbers of trapped ion groups worldwide, a myriad of trap architectures are currently in use. Applications of trapped ions include: quantum simulation, computing and networking, time standards and fundamental studies in quantum dynamics. Design of such traps is driven by these various research aims, but some universally desirable properties have lead to the development of ion trap foundries. Additionally, the excellent control achievable with trapped ions and the ability to do photonic readout has allowed progress on quantum networking using entanglement between remotely situated ion-based nodes. Here, we present a selection of trap architectures currently in use by the community and present their most salient characteristics, identifying features particularly suited for quantum networking. We also discuss our own in-house research efforts aimed at long-distance trapped ion networking.

  11. In search of global leaders. (United States)

    Green, Stephen; Hassan, Fred; Immelt, Jeffrey; Marks, Michael; Meiland, Daniel


    For all the talk about global organizations and executives, there's no definitive answer to the question of what we really mean by "global." A presence in multiple countries? Cultural adaptability? A multilingual top team? We asked four CEOs and the head of an international recruiting agency--HSBC's Stephen Green, Schering-Plough's Fred Hassan, GE's Jeffrey-lmmelt, Flextronics's Michael Marks, and Egon Zehnder's Daniel Meiland--to tell us what they think. They share some common ground. They all agree, for example, that the shift from a local to a global marketplace is irreversible and gaining momentum. "We're losing sight of the reality of globalization. But we should pay attention, because national barriers are quickly coming down", Daniel Meiland says. "If you look ahead five or ten years, the people with the top jobs in large corporations ... will be those who have lived in several cultures and who can converse in at least two languages." But the CEOs also disagree on many issues--on the importance of overseas assignments, for instance, and on the degree to which you need to adhere to local cultural norms. Some believe strongly that the global leader should, as a prerequisite to the job, live and work in other countries. As Stephen Green put it, "If you look at the executives currently running [HSBC's] largest businesses, all of them have worked in more than one, and nearly all in more than two, major country markets." Others downplay the importance of overseas assignments. "Putting people in foreign settings doesn't automatically imbue new attitudes, and it is attitudes rather than experiences that make a culture global," says Fred Hassan. The executives' essays capture views that are as diverse and multidimensional as the companies they lead.

  12. Identification of genome-wide non-canonical spliced regions and analysis of biological functions for spliced sequences using Read-Split-Fly. (United States)

    Bai, Yongsheng; Kinne, Jeff; Ding, Lizhong; Rath, Ethan C; Cox, Aaron; Naidu, Siva Dharman


    It is generally thought that most canonical or non-canonical splicing events involving U2- and U12 spliceosomes occur within nuclear pre-mRNAs. However, the question of whether at least some U12-type splicing occurs in the cytoplasm is still unclear. In recent years next-generation sequencing technologies have revolutionized the field. The "Read-Split-Walk" (RSW) and "Read-Split-Run" (RSR) methods were developed to identify genome-wide non-canonical spliced regions including special events occurring in cytoplasm. As the significant amount of genome/transcriptome data such as, Encyclopedia of DNA Elements (ENCODE) project, have been generated, we have advanced a newer more memory-efficient version of the algorithm, "Read-Split-Fly" (RSF), which can detect non-canonical spliced regions with higher sensitivity and improved speed. The RSF algorithm also outputs the spliced sequences for further downstream biological function analysis. We used open access ENCODE project RNA-Seq data to search spliced intron sequences against the U12-type spliced intron sequence database to examine whether some events could occur as potential signatures of U12-type splicing. The check was performed by searching spliced sequences against 5'ss and 3'ss sequences from the well-known orthologous U12-type spliceosomal intron database U12DB. Preliminary results of searching 70 ENCODE samples indicated that the presence of 5'ss with U12-type signature is more frequent than U2-type and prevalent in non-canonical junctions reported by RSF. The selected spliced sequences have also been further studied using miRBase to elucidate their functionality. Preliminary results from 70 samples of ENCODE datasets show that several miRNAs are prevalent in studied ENCODE samples. Two of these are associated with many diseases as suggested in the literature. Specifically, hsa-miR-1273 and hsa-miR-548 are associated with many diseases and cancers. Our RSF pipeline is able to detect many possible junctions

  13. Sequence Analysis of In Vivo-Expressed HIV-1 Spliced RNAs Reveals the Usage of New and Unusual Splice Sites by Viruses of Different Subtypes. (United States)

    Vega, Yolanda; Delgado, Elena; de la Barrera, Jorge; Carrera, Cristina; Zaballos, Ángel; Cuesta, Isabel; Mariño, Ana; Ocampo, Antonio; Miralles, Celia; Pérez-Castro, Sonia; Álvarez, Hortensia; López-Miragaya, Isabel; García-Bodas, Elena; Díez-Fuertes, Francisco; Thomson, Michael M


    HIV-1 RNAs are generated through a complex splicing mechanism, resulting in a great diversity of transcripts, which are classified in three major categories: unspliced, singly spliced (SS), and doubly spliced (DS). Knowledge on HIV-1 RNA splicing in vivo and by non-subtype B viruses is scarce. Here we analyze HIV-1 RNA splice site usage in CD4+CD25+ lymphocytes from HIV-1-infected individuals through pyrosequencing. HIV-1 DS and SS RNAs were amplified by RT-PCR in 19 and 12 samples, respectively. 13,108 sequences from HIV-1 spliced RNAs, derived from viruses of five subtypes (A, B, C, F, G), were identified. In four samples, three of non-B subtypes, five 3' splice sites (3'ss) mapping to unreported positions in the HIV-1 genome were identified. Two, designated A4i and A4j, were used in 22% and 25% of rev RNAs in two viruses of subtypes B and A, respectively. Given their close proximity (one or two nucleotides) to A4c and A4d, respectively, they could be viewed as variants of these sites. Three 3'ss, designated A7g, A7h, and A7i, located 20, 32, and 18 nucleotides downstream of A7, respectively, were identified in a subtype C (A7g, A7h) and a subtype G (A7i) viruses, each in around 2% of nef RNAs. The new splice sites or variants of splice sites were associated with the usual sequence features of 3'ss. Usage of unusual 3'ss A4d, A4e, A5a, A7a, and A7b was also detected. A4f, previously identified in two subtype C viruses, was preferentially used by rev RNAs of a subtype C virus. These results highlight the great diversity of in vivo splice site usage by HIV-1 RNAs. The fact that four of five newly identified splice sites or variants of splice sites were detected in non-subtype B viruses allows anticipating an even greater diversity of HIV-1 splice site usage than currently known.

  14. Barriers to Achieving Mentally Agile Junior Leaders

    National Research Council Canada - National Science Library

    Blocker, Marlon D


    ... that concept into clear, simple language to subordinates. How is it possible that the Army is still seeking the agile leaders it requires after our most senior leadership identified their need over eight years ago...

  15. Developing educational leaders: A partnership between two ...

    African Journals Online (AJOL)

    Developing educational leaders: A partnership between two universities to bring about system-wide change. ... towards improved learner performance. Keywords: educational leadership; intervention; leadership development; partnership; principal; school district; systemic change; systems theory; system-wide change ...

  16. An Undergraduate Foundation for Strategic Leaders

    National Research Council Canada - National Science Library

    Bedey, David


    .... Development of strategic leaders is a long-term process that also includes education and training in branch schools, command and staff colleges, and senior service colleges, as well as experience...

  17. Gender differences in Assessments of Party Leaders

    DEFF Research Database (Denmark)

    Kosiara-Pedersen, Karina; Hansen, Kasper Møller


    Is there a relationship between party leader gender and voters' assessments? Yes, according to theses on gender identity and stereotyping. A voter survey during the 2011 Danish general election allows for a comprehensive analysis of a less likely case with four male and four female party leaders...... of gender does not increase with age, actually, the opposite is the case among men since younger male voters have smaller sympathy for female party leaders. Furthermore, there is no support for the expectation that voters with more education or with higher levels of political interest and knowledge are more...... positive towards party leaders of their own gender than voters with less education. Also, the relationship between gender and voters’ assessments is not stronger prior to the election campaign than immediately after the election. Hence, in sum, gender identity does not seem to require a higher level...

  18. Yelavarthy Nayudamma: Scientist, Leader, and Mentor Extraordinary

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 10. Yelavarthy Nayudamma: Scientist, Leader, and Mentor Extraordinary. J Raghava Rao T Ramasami. General Article Volume 19 Issue 10 October 2014 pp 887-899 ...

  19. LEADER jõudis Eestisse / Harda Roosna

    Index Scriptorium Estoniae

    Roosna, Harda, 1956-


    EL-i maaelu toetusprogrammi LEADER+ rakendamist on katsetatud Põlva-, Valga-, Pärnu- ja Võrumaal. Hiiumaal arutletakse programmi rakendamiseks vajaliku tegevusgrupi moodustamise üle märtsis. Lisad: Ajalugu; Näited

  20. Interprofessional Care and Role of Team Leaders. (United States)

    Kaini, B K


    Interprofessional care is an essential part of the health service delivery system. It helps to achieve improved care and to deliver the optimal and desired health outcomes by working together, sharing and learning skills. Health care organisation is a collective sum of many leaders and followers. Successful delivery of interprofessional care relies on the contribution of interprofessional care team leaders and health care professionals from all groups. The role of the interprofessional care team leader is vital to ensuring continuity and consistency of care and to mobilise and motivate health care professionals for the effective delivery of health services. Medical professionals usually lead interprofessional care teams. Interprofessional care leaders require various skills and competencies for the successful delivery of interprofessional care.

  1. LTG Timothy J. Maude: Leader of Change

    National Research Council Canada - National Science Library

    Semeraro, Karen


    .... He was a leader of extraordinary vision, keen technical competency, and superb interpersonal skills all of which were directly shaped by a military career that included almost every key developmental...

  2. Activation of Antitumorigenic Stat3beta in Breast Cancer by Splicing Redirection (United States)


    the dual role of these proteins can be exploited by splicing re-direction approaches to manipulate their expression, in order to simultaneously...55 Wang, Z. et al. (2012) Manipulation of PK-M mutually exclusive alternative splicing by antisense oligonucleotides. Open Biol 2 (10), 120133 antisense-mediated shift of Bcl-x pre-mRNA splicing and antineoplastic agents. J Biol Chem 277 (51), 49374-49382 64 Bauman, J.A. et al. (2010

  3. Antagonistic factors control the unproductive splicing of SC35 terminal intron


    Dreumont, Natacha; Hardy, Sara; Behm-Ansmant, Isabelle; Kister, Liliane; Branlant, Christiane; St?venin, James; Bourgeois, Cyril F.


    Alternative splicing is regulated in part by variations in the relative concentrations of a variety of factors, including serine/arginine-rich (SR) proteins. The SR protein SC35 self-regulates its expression by stimulating unproductive splicing events in the 3? untranslated region of its own pre-mRNA. Using various minigene constructs containing the terminal retained intron and flanking exons, we identified in the highly conserved last exon a number of exonic splicing enhancer elements respon...

  4. Clinical significance of intronic variants in BRAF inhibitor resistant melanomas with altered BRAF transcript splicing


    Pupo, Gulietta M.; Boyd, Suzanah C.; Fung, Carina; Carlino, Matteo S.; Menzies, Alexander M.; Pedersen, Bernadette; Johansson, Peter; Hayward, Nicholas K.; Kefford, Richard F.; Scolyer, Richard A.; Long, Georgina V.; Rizos, Helen


    Alternate BRAF splicing is the most common mechanism of acquired resistance to BRAF inhibitor treatment in melanoma. Recently, alternate BRAF exon 4?8 splicing was shown to involve an intronic mutation, located 51 nucleotides upstream of BRAF exon 9 within a predicted splicing branch point. This intronic mutation was identified in a single cell line but has not been examined in vivo. Herein we demonstrate that in three melanomas biopsied from patients with acquired resistance to BRAF inhibito...

  5. Investigation of tissue-specific human orthologous alternative splice events in pig

    DEFF Research Database (Denmark)

    Hillig, Ann-Britt Nygaard; Jørgensen, Claus Bøttcher; Salicio, Susanna Cirera


    Alternative splicing of pre-mRNA can contribute to differences between tissues or cells either by regulating gene expression or creating proteins with various functions encoded by one gene. The number of investigated alternative splice events in pig has so far been limited. In this study we have ...... in preservation of open reading frame are indicative of a functional significance of the splice variants of the gene....

  6. Leaders as Corporate Responsibility Spokesperson: How Leaders Explain Liabilites Via Corporate Web Sites?

    Directory of Open Access Journals (Sweden)

    Burcu Öksüz


    Full Text Available The aim of this paper is to reveal the corporate social responsibility (CSR understandings of corporations from the leaders’ perspective and discuss how leaders define and explain CSR practices their organizations executed as spokesperson via social media channels of their organizations.  In this context, a content analysis aiming to display the ideas of Turkey’s top 250 corporations’ leaders (CEO, chairman of the board, general manager designated by Istanbul Chamber of Industry in 2013. The leader messages about different dimensions of CSR and CSR practices that are partaking in corporate web sites were examined. According to the results of the analysis, it is found that the leaders act as responsible leaders, and also the spokesperson of their corporations. In addition it is found out that responsible leaders included multiplexed information on different dimensions and various practices of CSR in their social media messages.

  7. Developing Senior Leaders for the Reserve Components (United States)


    For more information on the Forces and Resources Policy Center, see or contact the director (contact information is provided on the web page ). ...some combination of experiences, education, and personal development. Each has an extensive concept of develop- ment—how they define it, what ...policy. First, in what ways can the develop- ment of RC senior leaders be improved? Second, in what ways can reserve component leader development

  8. Implicit leadership theories : think leader, think effective?


    Schyns, B.; Schilling, J.


    In general, although research into leadership acknowledges negative aspects of leadership, research into implicit leadership theories lags behind in this respect. Most implicit leadership theories research implies that the image of a leader in general reflects an effective leader. However, recent results in leadership research as well as headlines and reports in the popular press cast doubt on this assumption. This article reports a qualitative study, focusing on general implicit leadership t...

  9. Understanding leader representations: Beyond implicit leadership theory


    Knee, Robert Everett


    The purpose of the present study was to establish evidence for the suggested integration of the theories of connectionism and leadership. Recent theoretical writings in the field of leadership have suggested that the dynamic representations generated by the connectionist perspective is an appropriate approach to understanding how we perceive leaders. Similarly, implicit leadership theory (ILT) explains that our cognitive understandings of leaders are based on a cognitive structure that we u...

  10. Interprofessional Care and Role of Team Leaders


    Bachchu Kailash Kaini


    Interprofessional care is an essential part of the health service delivery system. It helps to achieve improved care and to deliver the optimal and desired health outcomes by working together, sharing and learning skills. Health care organisation is a collective sum of many leaders and followers. Successful delivery of interprofessional care relies on the contribution of interprofessional care team leaders and health care professionals from all groups. The role of the interprofessional care t...

  11. Microfabricated linear Paul-Straubel ion trap (United States)

    Mangan, Michael A [Albuquerque, NM; Blain, Matthew G [Albuquerque, NM; Tigges, Chris P [Albuquerque, NM; Linker, Kevin L [Albuquerque, NM


    An array of microfabricated linear Paul-Straubel ion traps can be used for mass spectrometric applications. Each ion trap comprises two parallel inner RF electrodes and two parallel outer DC control electrodes symmetric about a central trap axis and suspended over an opening in a substrate. Neighboring ion traps in the array can share a common outer DC control electrode. The ions confined transversely by an RF quadrupole electric field potential well on the ion trap axis. The array can trap a wide array of ions.

  12. Splice of photonic crystal fibres by use of double phase-conjugate mirror (United States)

    Nakayama, Yusuke; Okamoto, Atsushi; Takayama, Yoshihisa; Hayano, Yutaka


    We present a novel splicing method for photonic crystal fibres (PCFs) with a double phase-conjugate mirror (DPCM). The DPCM is an optical device with photorefractive crystal (PRC) which generates phase-conjugate beams easily. In this report, we experimentally measure the splice losses of the DPCM for transverse PCF offset. We numerically estimate the splice losses in the case that butt coupled PCFs without DPCM. Comparing the experimental and numerical values of the splice loss of PCFs, we discuss the tolerance of the DPCM for the PCF displacement. Also, we discuss the causes of loss inside the DPCM module.

  13. Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

    Directory of Open Access Journals (Sweden)

    Michael Seiler


    Full Text Available Summary: Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA, and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like, or hotspot mutation profile (oncogene-like. Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis. : Seiler et al. report that 119 splicing factor genes carry putative driver mutations over 33 tumor types in TCGA. The most common mutations appear to be mutually exclusive and are associated with lineage-independent altered splicing. Samples with these mutations show deregulation of cell-autonomous pathways and immune infiltration. Keywords: splicing, SF3B1, U2AF1, SRSF2, RBM10, FUBP1, cancer, mutation

  14. Quantification of pre-mRNA escape rate and synergy in splicing. (United States)

    Bonde, Marie Mi; Voegeli, Sylvia; Baudrimont, Antoine; Séraphin, Bertrand; Becskei, Attila


    Splicing reactions generally combine high speed with accuracy. However, some of the pre-mRNAs escape the nucleus with a retained intron. Intron retention can control gene expression and increase proteome diversity. We calculated the escape rate for the yeast PTC7 intron and pre-mRNA. This prediction was facilitated by the observation that splicing is a linear process and by deriving simple algebraic expressions from a model of co- and post-transcriptional splicing and RNA surveillance that determines the rate of the nonsense-mediated decay (NMD) of the pre-mRNAs with the retained intron. The escape rate was consistent with the observed threshold of splicing rate below which the mature mRNA level declined. When an mRNA contains multiple introns, the outcome of splicing becomes more difficult to predict since not only the escape rate of the pre-mRNA has to be considered, but also the possibility that the splicing of each intron is influenced by the others. We showed that the two adjacent introns in the SUS1 mRNA are spliced cooperatively, but this does not counteract the escape of the partially spliced mRNA. These findings will help to infer promoter activity and to predict the behavior of and to control splicing regulatory networks. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. ulfasQTL: an ultra-fast method of composite splicing QTL analysis. (United States)

    Yang, Qian; Hu, Yue; Li, Jun; Zhang, Xuegong


    Alternative splicing plays important roles in many regulatory processes and diseases in human. Many genetic variants contribute to phenotypic differences in gene expression and splicing that determine variations in human traits. Detecting genetic variants that affect splicing phenotypes is essential for understanding the functional impact of genetic variations on alternative splicing. For many situations, the key phenotype is the relative splicing ratios of alternative isoforms rather than the expression values of individual isoforms. Splicing quantitative trait loci (sQTL) analysis methods have been proposed for detecting associations of genetic variants with the vectors of isoform splicing ratios of genes. We call this task as composite sQTL analysis. Existing methods are computationally intensive and cannot scale up for whole genome analysis. We developed an ultra-fast method named ulfasQTL for this task based on a previous method sQTLseekeR. It transforms tests of splicing ratios of multiple genes to a matrix form for efficient computation, and therefore can be applied for sQTL analysis at whole-genome scales at the speed thousands times faster than the existing method. We tested ulfasQTL on the data from the GEUVADIS project and compared it with an existing method. ulfasQTL is a very efficient tool for composite splicing QTL analysis and can be applied on whole-genome analysis with acceptable time.

  16. The proper splicing of RNAi factors is critical for pericentric heterochromatin assembly in fission yeast.

    Directory of Open Access Journals (Sweden)

    Scott P Kallgren

    Full Text Available Heterochromatin preferentially assembles at repetitive DNA elements, playing roles in transcriptional silencing, recombination suppression, and chromosome segregation. The RNAi machinery is required for heterochromatin assembly in a diverse range of organisms. In fission yeast, RNA splicing factors are also required for pericentric heterochromatin assembly, and a prevailing model is that splicing factors provide a platform for siRNA generation independently of their splicing activity. Here, by screening the fission yeast deletion library, we discovered four novel splicing factors that are required for pericentric heterochromatin assembly. Sequencing total cellular RNAs from the strongest of these mutants, cwf14Δ, showed intron retention in mRNAs of several RNAi factors. Moreover, introducing cDNA versions of RNAi factors significantly restored pericentric heterochromatin in splicing mutants. We also found that mutations of splicing factors resulted in defective telomeric heterochromatin assembly and mis-splicing the mRNA of shelterin component Tpz1, and that replacement of tpz1+ with its cDNA partially rescued heterochromatin defects at telomeres in splicing mutants. Thus, proper splicing of RNAi and shelterin factors contributes to heterochromatin assembly at pericentric regions and telomeres.

  17. Trans-Splicing Improvement by the Combined Application of Antisense Strategies

    Directory of Open Access Journals (Sweden)

    Ulrich Koller


    Full Text Available Spliceosome-mediated RNA trans-splicing has become an emergent tool for the repair of mutated pre-mRNAs in the treatment of genetic diseases. RNA trans-splicing molecules (RTMs are designed to induce a specific trans-splicing reaction via a binding domain for a respective target pre-mRNA region. A previously established reporter-based screening system allows us to analyze the impact of various factors on the RTM trans-splicing efficiency in vitro. Using this system, we are further able to investigate the potential of antisense RNAs (AS RNAs, presuming to improve the trans-splicing efficiency of a selected RTM, specific for intron 102 of COL7A1. Mutations in the COL7A1 gene underlie the dystrophic subtype of the skin blistering disease epidermolysis bullosa (DEB. We have shown that co-transfections of the RTM and a selected AS RNA, interfering with competitive splicing elements on a COL7A1-minigene (COL7A1-MG, lead to a significant increase of the RNA trans-splicing efficiency. Thereby, accurate trans-splicing between the RTM and the COL7A1-MG is represented by the restoration of full-length green fluorescent protein GFP on mRNA and protein level. This mechanism can be crucial for the improvement of an RTM-mediated correction, especially in cases where a high trans-splicing efficiency is required.

  18. Non-sequential and multi-step splicing of the dystrophin transcript. (United States)

    Gazzoli, Isabella; Pulyakhina, Irina; Verwey, Nisha E; Ariyurek, Yavuz; Laros, Jeroen F J; 't Hoen, Peter A C; Aartsma-Rus, Annemieke


    The dystrophin protein encoding DMD gene is the longest human gene. The 2.2 Mb long human dystrophin transcript takes 16 hours to be transcribed and is co-transcriptionally spliced. It contains long introns (24 over 10kb long, 5 over 100kb long) and the heterogeneity in intron size makes it an ideal transcript to study different aspects of the human splicing process. Splicing is a complex process and much is unknown regarding the splicing of long introns in human genes. Here, we used ultra-deep transcript sequencing to characterize splicing of the dystrophin transcripts in 3 different human skeletal muscle cell lines, and explored the order of intron removal and multi-step splicing. Coverage and read pair analyses showed that around 40% of the introns were not always removed sequentially. Additionally, for the first time, we report that non-consecutive intron removal resulted in 3 or more joined exons which are flanked by unspliced introns and we defined these joined exons as an exon block. Lastly, computational and experimental data revealed that, for the majority of dystrophin introns, multistep splicing events are used to splice out a single intron. Overall, our data show for the first time in a human transcript, that multi-step intron removal is a general feature of mRNA splicing.

  19. Indeterminacy, sunspots, and development traps

    Czech Academy of Sciences Publication Activity Database

    Slobodyan, Sergey


    Roč. 29, 1-2 (2005), s. 159-185 ISSN 0165-1889 Institutional research plan: CEZ:AV0Z70850503 Keywords : indeterminacy * development trap * stochastic stability Subject RIV: AH - Economics Impact factor: 0.691, year: 2005

  20. Efficiency of antlion trap construction. (United States)

    Fertin, Arnold; Casas, Jérôme


    Assessing the architectural optimality of animal constructions is in most cases extremely difficult, but is feasible for antlion larvae, which dig simple pits in sand to catch ants. Slope angle, conicity and the distance between the head and the trap bottom, known as off-centring, were measured using a precise scanning device. Complete attack sequences in the same pits were then quantified, with predation cost related to the number of behavioural items before capture. Off-centring leads to a loss of architectural efficiency that is compensated by complex attack behaviour. Off-centring happened in half of the cases and corresponded to post-construction movements. In the absence of off-centring, the trap is perfectly conical and the angle is significantly smaller than the crater angle, a physical constant of sand that defines the steepest possible slope. Antlions produce efficient traps, with slopes steep enough to guide preys to their mouths without any attack, and shallow enough to avoid the likelihood of avalanches typical of crater angles. The reasons for the paucity of simplest and most efficient traps such as theses in the animal kingdom are discussed.

  1. Quantum computing with trapped ions

    International Nuclear Information System (INIS)

    Haeffner, H.; Roos, C.F.; Blatt, R.


    Quantum computers hold the promise of solving certain computational tasks much more efficiently than classical computers. We review recent experimental advances towards a quantum computer with trapped ions. In particular, various implementations of qubits, quantum gates and some key experiments are discussed. Furthermore, we review some implementations of quantum algorithms such as a deterministic teleportation of quantum information and an error correction scheme

  2. Efficiency of subaquatic light traps

    Czech Academy of Sciences Publication Activity Database

    Ditrich, Tomáš; Čihák, P.


    Roč. 38, č. 3 (2017), s. 171-184 ISSN 0165-0424 R&D Projects: GA ČR(CZ) GA14-29857S Institutional support: RVO:60077344 Keywords : Heteroptera * Diptera * light trap Subject RIV: EH - Ecology, Behaviour OBOR OECD: Ecology Impact factor: 0.524, year: 2016

  3. Quantum Games in ion traps

    International Nuclear Information System (INIS)

    Buluta, Iulia Maria; Fujiwara, Shingo; Hasegawa, Shuichi


    We propose a general, scalable framework for implementing two-choices-multiplayer Quantum Games in ion traps. In particular, we discuss two famous examples: the Quantum Prisoners' Dilemma and the Quantum Minority Game. An analysis of decoherence due to intensity fluctuations in the applied laser fields is also provided

  4. The rise of trapped populations

    Directory of Open Access Journals (Sweden)

    April T Humble


    Full Text Available As border security increases and borders become less permeable, cross-border migration is becoming increasingly difficult, selective and dangerous. Growing numbers of people are becoming trapped in their own countries or in transit countries, or being forced to roam border areas, unable to access legal protection or basic social necessities.

  5. Quantum Games in ion traps

    Energy Technology Data Exchange (ETDEWEB)

    Buluta, Iulia Maria [Department of Quantum Engineering and Systems Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)]. E-mail:; Fujiwara, Shingo [Department of Quantum Engineering and Systems Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)]. E-mail:; Hasegawa, Shuichi [Department of Quantum Engineering and Systems Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)]. E-mail:


    We propose a general, scalable framework for implementing two-choices-multiplayer Quantum Games in ion traps. In particular, we discuss two famous examples: the Quantum Prisoners' Dilemma and the Quantum Minority Game. An analysis of decoherence due to intensity fluctuations in the applied laser fields is also provided.

  6. Leader narcissism and follower outcomes: The counterbalancing effect of leader humility. (United States)

    Owens, Bradley P; Wallace, Angela S; Walker, Angela S; Waldman, David A


    [Correction Notice: An Erratum for this article was reported in Vol 100(4) of Journal of Applied Psychology (see record 2015-29666-001). The last name of the second author was misspelled in the Online First version of the article. All versions of this article have been corrected.] In response to recent calls to theorize and examine how multiple leader characteristics may work together in their effects, the current research examines how leader narcissism and humility interact to predict perceived leader effectiveness and follower (i.e., direct-report) job engagement and performance. Although an examination of leaders who are narcissistic yet humble may seem oxymoronic and even paradoxical, researchers have suggested that seemingly contradictory personal attributes may exist simultaneously and may actually work together to produce positive outcomes. Results from survey data from followers and leaders working for a large health insurance organization showed that the interaction of leader narcissism and leader humility is associated with perceptions of leader effectiveness, follower job engagement, and subjective and objective follower job performance. Together, these results suggest that narcissistic leaders can have positive effects on followers when their narcissism is tempered by humility. (c) 2015 APA, all rights reserved).

  7. Two novel splicing mutations in the SLC45A2 gene cause Oculocutaneous Albinism Type IV by unmasking cryptic splice sites. (United States)

    Straniero, Letizia; Rimoldi, Valeria; Soldà, Giulia; Mauri, Lucia; Manfredini, Emanuela; Andreucci, Elena; Bargiacchi, Sara; Penco, Silvana; Gesu, Giovanni P; Del Longo, Alessandra; Piozzi, Elena; Asselta, Rosanna; Primignani, Paola


    Oculocutaneous albinism (OCA) is characterized by hypopigmentation of the skin, hair and eye, and by ophthalmologic abnormalities caused by a deficiency in melanin biosynthesis. OCA type IV (OCA4) is one of the four commonly recognized forms of albinism, and is determined by mutation in the SLC45A2 gene. Here, we investigated the genetic basis of OCA4 in an Italian child. The mutational screening of the SLC45A2 gene identified two novel potentially pathogenic splicing mutations: a synonymous transition (c.888G>A) involving the last nucleotide of exon 3 and a single-nucleotide insertion (c.1156+2dupT) within the consensus sequence of the donor splice site of intron 5. As computer-assisted analysis for mutant splice-site prediction was not conclusive, we investigated the effects on pre-mRNA splicing of these two variants by using an in vitro minigene approach. Production of mutant transcripts in HeLa cells demonstrated that both mutations cause the almost complete abolishment of the physiologic donor splice site, with the concomitant unmasking of cryptic donor splice sites. To our knowledge, this work represents the first in-depth molecular characterization of splicing defects in a OCA4 patient.

  8. Targeted RNA-Seq profiling of splicing pattern in the DMD gene: exons are mostly constitutively spliced in human skeletal muscle. (United States)

    Bougé, Anne-Laure; Murauer, Eva; Beyne, Emmanuelle; Miro, Julie; Varilh, Jessica; Taulan, Magali; Koenig, Michel; Claustres, Mireille; Tuffery-Giraud, Sylvie


    We have analysed the splicing pattern of the human Duchenne Muscular Dystrophy (DMD) NB transcript in normal skeletal muscle. To achieve depth of coverage required for the analysis of this lowly expressed gene in muscle, we designed a targeted RNA-Seq procedure that combines amplification of the full-length 11.3 kb DMD cDNA sequence and 454 sequencing technology. A high and uniform coverage of the cDNA sequence was obtained that allowed to draw up a reliable inventory of the physiological alternative splicing events in the muscular DMD transcript. In contrast to previous assumptions, we evidenced that most of the 79 DMD exons are constitutively spliced in skeletal muscle. Only a limited number of 12 alternative splicing events were identified, all present at a very low level. These include previously known exon skipping events but also newly described pseudoexon inclusions and alternative 3' splice sites, of which one is the first functional NAGNAG splice site reported in the DMD gene. This study provides the first RNA-Seq-based reference of DMD splicing pattern in skeletal muscle and reports on an experimental procedure well suited to detect condition-specific differences in this low abundance transcript that may prove useful for diagnostic, research or RNA-based therapeutic applications.

  9. Developmental regulation of tau splicing is disrupted in stem cell-derived neurons from frontotemporal dementia patients with the 10 + 16 splice-site mutation in MAPT. (United States)

    Sposito, Teresa; Preza, Elisavet; Mahoney, Colin J; Setó-Salvia, Núria; Ryan, Natalie S; Morris, Huw R; Arber, Charles; Devine, Michael J; Houlden, Henry; Warner, Thomas T; Bushell, Trevor J; Zagnoni, Michele; Kunath, Tilo; Livesey, Frederick J; Fox, Nick C; Rossor, Martin N; Hardy, John; Wray, Selina


    The alternative splicing of the tau gene, MAPT, generates six protein isoforms in the adult human central nervous system (CNS). Tau splicing is developmentally regulated and dysregulated in disease. Mutations in MAPT that alter tau splicing cause frontotemporal dementia (FTD) with tau pathology, providing evidence for a causal link between altered tau splicing and disease. The use of induced pluripotent stem cell (iPSC)-derived neurons has revolutionized the way we model neurological disease in vitro. However, as most tau mutations are located within or around the alternatively spliced exon 10, it is important that iPSC-neurons splice tau appropriately in order to be used as disease models. To address this issue, we analyzed the expression and splicing of tau in iPSC-derived cortical neurons from control patients and FTD patients with the 10 + 16 intronic mutation in MAPT. We show that control neurons only express the fetal tau isoform (0N3R), even at extended time points of 100 days in vitro. Neurons from FTD patients with the 10 + 16 mutation in MAPT express both 0N3R and 0N4R tau isoforms, demonstrating that this mutation overrides the developmental regulation of exon 10 inclusion in our in vitro model. Further, at extended time points of 365 days in vitro, we observe a switch in tau splicing to include six tau isoforms as seen in the adult human CNS. Our results demonstrate the importance of neuronal maturity for use in in vitro modeling and provide a system that will be important for understanding the functional consequences of altered tau splicing. © The Author 2015. Published by Oxford University Press.

  10. 29 CFR 780.331 - Crew leaders and labor contractors. (United States)


    ... 29 Labor 3 2010-07-01 2010-07-01 false Crew leaders and labor contractors. 780.331 Section 780.331... 13(a)(6) Statutory Provisions § 780.331 Crew leaders and labor contractors. (a) Whether a crew leader... contractor. A crew leader who merely assembles a crew and brings them to the farm to be supervised and paid...

  11. 20 CFR 404.1010 - Farm crew leader as employer. (United States)


    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Farm crew leader as employer. 404.1010....1010 Farm crew leader as employer. A farm crew leader furnishes workers to do agricultural labor for another person, usually a farm operator. If the crew leader pays the workers (the money can be the crew...

  12. Leader Communication Style: Effects on Members of Small Groups. (United States)

    Barlow, Sally; And Others


    Determined effects of different leader verbal styles on group members. Results indicated leader verbal style is a factor influencing communication style of members and that it affects members' perceptions of leader orientation; however, it does not affect members' satisfaction with leaders, nor the self-concept of group members. (Author/RC)

  13. Scaling ion traps for quantum computing

    CSIR Research Space (South Africa)

    Uys, H


    Full Text Available The design, fabrication and preliminary testing of a chipscale, multi-zone, surface electrode ion trap is reported. The modular design and fabrication techniques used are anticipated to advance scalability of ion trap quantum computing architectures...

  14. Proteomic analysis of Entamoeba histolytica in vivo assembled pre-mRNA splicing complexes. (United States)

    Valdés, Jesús; Nozaki, Tomoyoshi; Sato, Emi; Chiba, Yoko; Nakada-Tsukui, Kumiko; Villegas-Sepúlveda, Nicolás; Winkler, Robert; Azuara-Liceaga, Elisa; Mendoza-Figueroa, María Saraí; Watanabe, Natsuki; Santos, Herbert J; Saito-Nakano, Yumiko; Galindo-Rosales, José Manuel


    The genome of the human intestinal parasite Entamoeba histolytica contains nearly 3000 introns and bioinformatic predictions indicate that major and minor spliceosomes occur in Entamoeba. However, except for the U2-, U4-, U5- and U6 snRNAs, no other splicing factor has been cloned and characterized. Here, we HA-tagged cloned the snRNP component U1A and assessed its expression and nuclear localization. Because the snRNP-free U1A form interacts with polyadenylate-binding protein, HA-U1A immunoprecipitates could identify early and late splicing complexes. Avoiding Entamoeba's endonucleases and ensuring the precipitation of RNA-binding proteins, parasite cultures were UV cross-linked prior to nuclear fraction immunoprecipitations with HA antibodies, and precipitates were subjected to tandem mass spectrometry (MS/MS) analyses. To discriminate their nuclear roles (chromatin-, co-transcriptional-, splicing-related), MS/MS analyses were carried out with proteins eluted with MS2-GST-sepharose from nuclear extracts of an MS2 aptamer-tagged Rabx13 intron amoeba transformant. Thus, we probed thirty-six Entamoeba proteins corresponding to 32 cognate splicing-specific factors, including 13 DExH/D helicases required for all stages of splicing, and 12 different splicing-related helicases were identified also. Furthermore 50 additional proteins, possibly involved in co-transcriptional processes were identified, revealing the complexity of co-transcriptional splicing in Entamoeba. Some of these later factors were not previously found in splicing complex analyses. Numerous facts about the splicing of the nearly 3000 introns of the Entamoeba genome have not been unraveled, particularly the splicing factors and their activities. Considering that many of such introns are located in metabolic genes, the knowledge of the splicing cues has the potential to be used to attack or control the parasite. We have found numerous new splicing-related factors which could have therapeutic benefit. We

  15. Stokes Trap: Multiplexed particle trapping and manipulation using fluidics (United States)

    Shenoy, Anish; Schroeder, Charles

    We report the development of the Stokes Trap, which is a multiplexed microfluidic trap for control over an arbitrary number of small particles in a microfluidic device. Our work involves the design and implementation of ``smart'' flow-based devices by coupling feedback control with microfluidics, thereby enabling new routes for the fluidic-directed assembly of particles. Here, we discuss the development of a new method to achieve multiplexed microfluidic trapping of an arbitrary number of particles using the sole action of fluid flow. In particular, we use a Hele-Shaw microfluidic cell to generate hydrodynamic forces on particles in a viscous-dominated flow defined by the microdevice geometry and imposed peripheral flow rates. This platform allows for a high degree of flow control over individual particles and can be used for manufacturing novel particles for fundamental studies, using fluidic-directed assembly. From a broader perspective, our work provides a solid framework for guiding the design of next-generation, automated on-chip assays.

  16. The Use of Camera Traps in Wildlife


    Yasin Uçarlı; Bülent Sağlam


    Camera traps are increasingly used in the abundance and density estimates of wildlife species. Camera traps are very good alternative for direct observation in case, particularly, steep terrain, dense vegetation covered areas or nocturnal species. The main reason for the use of camera traps is eliminated that the economic, personnel and time loss in a continuous manner at the same time in different points. Camera traps, motion and heat sensitive, can take a photo or video according to the mod...

  17. Sympathetic Cooling of Trapped Cd+ Isotopes


    Blinov, B. B.; Deslauriers, L.; Lee, P.; Madsen, M. J.; Miller, R.; Monroe, C.


    We sympathetically cool a trapped 112Cd+ ion by directly Doppler-cooling a 114Cd+ ion in the same trap. This is the first demonstration of optically addressing a single trapped ion being sympathetically cooled by a different species ion. Notably, the experiment uses a single laser source, and does not require strong focusing. This paves the way toward reducing decoherence in an ion trap quantum computer based on Cd+ isotopes.

  18. Characterization of a splicing mutation in group A xeroderma pigmentosum

    International Nuclear Information System (INIS)

    Satokata, Ichiro; Tanaka, Kiyoji; Miura, Naoyuki; Miyamoto, Iwai; Okada, Yoshio; Satoh, Yoshiaki; Kondo, Seiji


    The molecular basis of group A xeroderma pigmentosum (WP) was investigated by comparison of the nucleotide sequences of multiple clones of the XP group A complementing gene (XPAC) from a patient with group A XP with that of a normal gene. The clones showed a G → C substitution at the 3' splice acceptor site of intron 3, which altered the obligatory AG acceptor dinucleotide to AC. Nucleotide sequencing of cDNAs amplified by the polymerase chain reaction revealed that this single base substitution abolishes the canonical 3' splice site, thus creating two abnormally spliced mRNA forms. The larger form is identical with normal mRNA except for a dinucleotide deletion at the 5' end of exon 4. This deletion results in a frameshift with premature translation termination in exon 4. The smaller form has a deletion of the entire exon 3 and the dinucleotide at the 5' end of exon 4. The result of a transfection study provided additional evidence that this single base substitution is the disease-causing mutation. This single base substitution creates a new cleavage site for the restriction nuclease AlwNI. Analysis of AlwNI restriction fragment length polymorphism showed a high frequency of this mutation in Japanese patients with group A XP: 16 of 21 unrelated Japanese patients were homozygous and 4 were heterozygous for this mutation. However, 11 Caucasians and 2 Blacks with group A XP did not have this mutant allele. The polymorphic AlwNI restriction fragments are concluded to be useful for diagnosis of group A XP in Japanese subjects, including prenatal cases and carriers

  19. Performance of Grouted Splice Sleeve Connector under Tensile Load

    Directory of Open Access Journals (Sweden)

    A. Alias


    Full Text Available The grouted splice sleeve connector system takes advantage of the bond-slip resistance of the grout and the mechanical gripping of reinforcement bars to provide resistance to tensile force. In this system, grout acts as a load-transferring medium and bonding material between the bars and sleeve. This study adopted the end-to-end rebars connection method to investigate the effect of development length and sleeve diameter on the bonding performance of the sleeve connector. The end-to-end method refers to the condition where reinforcement bars are inserted into the sleeve from both ends and meet at the centre before grout is filled. Eight specimens of grouted splice sleeve connector were tested under tensile load to determine their performance. The sleeve connector was designed using 5 mm thick circular hollow section (CHS steel pipe and consisted of one external and two internal sleeves. The tensile test results show that connectors with a smaller external and internal sleeve diameter appear to provide better bonding performance. Three types of failure were observed in this research, which are bar fracture (outside the sleeve, bar pullout, and internal sleeve pullout. With reference to these failure types, the development length of 200 mm is the optimum value due to its bar fracture type, which indicates that the tensile capacity of the connector is higher than the reinforcement bar. It is found that the performance of the grouted splice sleeve connector is influenced by the development length of the reinforcement bar and the diameter of the sleeve.

  20. Periostin shows increased evolutionary plasticity in its alternatively spliced region

    Directory of Open Access Journals (Sweden)

    Hoersch Sebastian


    Full Text Available Abstract Background Periostin (POSTN is a secreted extracellular matrix protein of poorly defined function that has been related to bone and heart development as well as to cancer. In human and mouse, it is known to undergo alternative splicing in its C-terminal region, which is devoid of known protein domains. Differential expression of periostin, sometimes of specific splicing isoforms, is observed in a broad range of human cancers, including breast, pancreatic, and colon cancer. Here, we combine genomic and transcriptomic sequence data from vertebrate organisms to study the evolution of periostin and particularly of its C-terminal region. Results We found that the C-terminal part of periostin is markedly more variable among vertebrates than the rest of periostin in terms of exon count, length, and splicing pattern, which we interpret as a consequence of neofunctionalization after the split between periostin and its paralog transforming growth factor, beta-induced (TGFBI. We also defined periostin's sequential 13-amino acid repeat units - well conserved in teleost fish, but more obscure in higher vertebrates - whose secondary structure is predicted to be consecutive beta strands. We suggest that these beta strands may mediate binding interactions with other proteins through an extended beta-zipper in a manner similar to the way repeat units in bacterial cell wall proteins have been reported to bind human fibronectin. Conclusions Our results, obtained with the help of the increasingly large collection of complete vertebrate genomes, document the evolutionary plasticity of periostin's C-terminal region, and for the first time suggest a basis for its functional role.

  1. Recurrent Hyperparathyroidism Due to a Novel CDC73 Splice Mutation. (United States)

    Hattangady, Namita Ganesh; Wilson, Tremika Le-Shan; Miller, Barbra Sue; Lerario, Antonio Marcondes; Giordano, Thomas James; Choksi, Palak; Else, Tobias


    The recognition of hereditary causes of primary hyperparathyroidism (pHPT) is important because clinical care and surveillance differ significantly between sporadic and hereditary pHPT. In addition, the increasing number of genetic tests poses a challenge to classify mutations as benign or pathogenic. Functional work-up of variants remains a mainstay to provide evidence for pathogenicity. We describe a 52-year-old male patient with recurrent pHPT since age 35 years. Despite several neck surgeries with complete parathyroidectomy, he experienced persistent pHPT, necessitating repeated surgery for a forearm autotransplant, which finally resulted in unmeasurable parathyroid hormone (PTH) levels. Genetic testing revealed a new CDC73 variant (c.238-8G>A [IVS2-8G>A]), initially classified as a variant of uncertain significance. Parathyroid tissue from the initial surgeries showed loss of heterozygosity. Using an RT-PCR approach, we show that the mutation leads to the use of a cryptic splice site in peripheral mononuclear cells. In addition, a minigene approach confirms the use of the cryptic splice site in a heterologous cell system. The novel c.238-8G>A CDC73 variant activates a cryptic splice site, and the functional data provided justify the classification as a likely pathogenic variant. Our results underscore the importance of functional work-up for variant classification in the absence of other available data, such as presence in disease-specific databases, other syndromic clinical findings, or family history. In addition, the presented case exemplifies the importance to consider a hereditary condition in young patients with pHPT, particularly those with multi-gland involvement. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  2. Resilient Women Educational Leaders in Turbulent Times: Applying the Leader Resilience Profile® to Assess Women's Leadership Strengths (United States)

    Reed, Diane E.; Blaine, Bruce


    Women leaders across the world confront a common challenge: extremely turbulent times that challenge even the most skillful leaders. The paper begins with a brief overview of the meaning of leader resilience and describes the resilience cycle that all leaders experience when adversity strikes. Five phases of the resilience cycle discussed are:…

  3. A Critical Analysis of Attribute Development Programs for Army Leaders (United States)


    intellectual curiosity, and creativity . Experience is where all the training and education are put into practice.66 Leader development is the...Train leaders in the art and science of mission command. 5. Train to develop adaptive leaders. 6. Train leaders to think critically and creatively ...demonstrate depth of content, knowledge, and teaching ability. Overall, CSF2 successfully utilizes all delivery domains and leader development

  4. Dynamic array of dark optical traps

    DEFF Research Database (Denmark)

    Daria, V.R.; Rodrigo, P.J.; Glückstad, J.


    A dynamic array of dark optical traps is generated for simultaneous trapping and arbitrary manipulation of multiple low-index microstructures. The dynamic intensity patterns forming the dark optical trap arrays are generated using a nearly loss-less phase-to-intensity conversion of a phase-encode...

  5. 50 CFR 31.16 - Trapping program. (United States)


    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Trapping program. 31.16 Section 31.16 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE... Disposal § 31.16 Trapping program. Except as hereafter noted, persons trapping animals on wildlife refuge...

  6. An Open Standard for Camera Trap Data

    NARCIS (Netherlands)

    Forrester, Tavis; O'Brien, Tim; Fegraus, Eric; Jansen, P.A.; Palmer, Jonathan; Kays, Roland; Ahumada, Jorge; Stern, Beth; McShea, William


    Camera traps that capture photos of animals are a valuable tool for monitoring biodiversity. The use of camera traps is rapidly increasing and there is an urgent need for standardization to facilitate data management, reporting and data sharing. Here we offer the Camera Trap Metadata Standard as an

  7. The Aarhus Ion Micro-Trap Project

    DEFF Research Database (Denmark)

    Miroshnychenko, Yevhen; Nielsen, Otto; Poulsen, Gregers

    and installed in an ultra high vacuum chamber, which includes an ablation oven for all-optical loading of the trap [2]. The next steps on the project are to demonstrate the operation of the micro-trap and the cooling of ions using fiber delivered light. [1] D. Grant, Development of Micro-Scale Ion traps, Master...

  8. Biased trapping issue on weighted hierarchical networks

    Indian Academy of Sciences (India)

    Using a method based on generating functions, we determine explicitly the mean first-passage time (MFPT) for the trapping issue. Let parameter (0 < < 1) be the weight factor. We show that the efficiency of the trapping process depends on the parameter a; the smaller the value of a, the more efficient is the trapping ...

  9. Revealing trap depth distributions in persistent phosphors

    NARCIS (Netherlands)

    Van den Eeckhout, K.; Bos, A.J.J.; Poelman, D.; Smet, P.F.


    Persistent luminescence or afterglow is caused by a gradual release of charge carriers from trapping centers. The energy needed to release these charge carriers is determined by the trap depths. Knowledge of these trap depths is therefore crucial in the understanding of the persistent luminescence

  10. Leadership and Leader Developmental Self-Efficacy: Their Role in Enhancing Leader Development Efforts. (United States)

    Murphy, Susan Elaine; Johnson, Stefanie K


    This chapter describes the role of two types of self-efficacy-leader self-efficacy and leader developmental efficacy-for enhancing leadership development. Practical implications for designing and developing leadership programs that take into account these two types of self-efficacy are discussed. © 2016 Wiley Periodicals, Inc., A Wiley Company.

  11. On ethically solvent leaders : The role of pride and moral identity in predicting ethical leader behavior

    NARCIS (Netherlands)

    Sanders, Stacey; Wisse, Barbara; Van Yperen, Nico W.; Rus, Diana


    The popular media has repeatedly pointed to pride as one of the key factors motivating leaders to behave unethically. However, given the devastating consequences that leader unethical behavior may have, a more scientific account of the role of pride is warranted. The present study differentiates

  12. A Comparison of Student Leader and Non Leader Attitudes Toward Legalizing Marihuana (United States)

    Bittner, John R.; Cash, William B.


    The data tends to imply that campus leaders have attitudes on the issue of marihuana legalization which conform to the norms of a major midwestern university sampling. Drug education programs might include student leaders with local credibility and who may possess attitudes very similar to their peers. (Author/BY)

  13. Twenty-Two Hispanic Leaders Discuss Poverty: Results from the Hispanic Leaders Study. (United States)

    Quiroz, Julia Teresa

    This study reports twenty-two Hispanic leaders' responses to interviews assessing their perspectives on the nature, prevalence, and causes of poverty among Hispanics. This report contains six parts. Part 1 is an introduction. Part 2 presents the methodology used in the study. Part 3 gives the leaders' demographic and educational backgrounds. Part…

  14. The Impact of Educational Change on School Leaders: Experiences of Pakistani School Leaders (United States)

    Razzaq, Jamila; Forde, Christine


    The Pakistani education system, like many other countries across the world, is going through a phase of concerted change in the first decade of the 21st century and school leaders are expected to play a crucial role in the management of this change programme. This article considers the impact of educational change on a group of school leaders who…

  15. Leaders' Personal Wisdom and Leader-Member Exchange Quality : The Role of Individualized Consideration

    NARCIS (Netherlands)

    Zacher, Hannes; Pearce, Liane K.; Rooney, David; McKenna, Bernard

    Business scholars have recently proposed that the virtue of personal wisdom may predict leadership behaviors and the quality of leader-follower relationships. This study investigated relationships among leaders' personal wisdom-defined as the integration of advanced cognitive, reflective, and

  16. IGF1 mRNA splicing variants in Liaoning cashmere goat: identification, characterization, and transcriptional patterns in skin and visceral organs. (United States)

    Bai, Wen L; Yin, Rong H; Yin, Rong L; Wang, Jiao J; Jiang, Wu Q; Luo, Guang B; Zhao, Zhi H


    Insulin-like growth factor I (IGF1) is a member of the insulin superfamily. It performs important roles in the proliferation and differentiation of skin cell and control of hair cycles and is thought to be a potential candidate gene for goat cashmere traits. In this work, we isolated and characterized three kinds of IGF1 mRNA splicing variants from the liver of Liaoning Cashmere goat, and the expression characterization of the IGF1 mRNA splicing variants were investigated in skin and other tissues of Liaoning cashmere goat. The sequencing results indicated that the classes 1w, 1, and 2 of IGF1 cDNAs in Liaoning cashmere goat, each included an open reading frame encoding the IGF1 precursor protein. The deduced amino acid sequences of the three IGF1 precursor proteins differed only in their NH2-terminal leader peptides. Through removal of the signal peptide and extension peptide, the three IGF1 mRNA splicing variants (classes 1w, 1, and 2) resulted in the same mature IGF1 protein in Liaoning cashmere goat. In skin tissue of Liaoning cashmere goat, class 1 and class 2 were detected in all stages of hair follicle cycling, and they had the highest transcription level at anagen, and then early anagen; whereas at telogen both classes 1 and 2 had the lowest expression in mRNA level, but the class 1 appears to be relatively more abundant than class 2 in skin tissue of Liaoning cashmere goat. However, the class 1w transcript was not detected in the skin tissues. Three classes of IGF1 mRNA were transcribed in a variety of tissues, including heart, brain, spleen, lung, kidney, liver, and skeletal muscle, but class 1 IGF1 mRNA was more abundant than classes 1w and 2 in the investigated tissues.

  17. Leaders in social networks, the Delicious case. (United States)

    Lü, Linyuan; Zhang, Yi-Cheng; Yeung, Chi Ho; Zhou, Tao


    Finding pertinent information is not limited to search engines. Online communities can amplify the influence of a small number of power users for the benefit of all other users. Users' information foraging in depth and breadth can be greatly enhanced by choosing suitable leaders. For instance in, users subscribe to leaders' collection which lead to a deeper and wider reach not achievable with search engines. To consolidate such collective search, it is essential to utilize the leadership topology and identify influential users. Google's PageRank, as a successful search algorithm in the World Wide Web, turns out to be less effective in networks of people. We thus devise an adaptive and parameter-free algorithm, the LeaderRank, to quantify user influence. We show that LeaderRank outperforms PageRank in terms of ranking effectiveness, as well as robustness against manipulations and noisy data. These results suggest that leaders who are aware of their clout may reinforce the development of social networks, and thus the power of collective search.

  18. Leaders in social networks, the Delicious case.

    Directory of Open Access Journals (Sweden)

    Linyuan Lü

    Full Text Available Finding pertinent information is not limited to search engines. Online communities can amplify the influence of a small number of power users for the benefit of all other users. Users' information foraging in depth and breadth can be greatly enhanced by choosing suitable leaders. For instance in, users subscribe to leaders' collection which lead to a deeper and wider reach not achievable with search engines. To consolidate such collective search, it is essential to utilize the leadership topology and identify influential users. Google's PageRank, as a successful search algorithm in the World Wide Web, turns out to be less effective in networks of people. We thus devise an adaptive and parameter-free algorithm, the LeaderRank, to quantify user influence. We show that LeaderRank outperforms PageRank in terms of ranking effectiveness, as well as robustness against manipulations and noisy data. These results suggest that leaders who are aware of their clout may reinforce the development of social networks, and thus the power of collective search.

  19. Leader affective presence and innovation in teams. (United States)

    Madrid, Hector P; Totterdell, Peter; Niven, Karen; Barros, Eduardo


    Affective presence is a novel personality construct that describes the tendency of individuals to make their interaction partners feel similarly positive or negative. We adopt this construct, together with the input-process-output model of teamwork, to understand how team leaders influence team interaction and innovation performance. In 2 multisource studies, based on 350 individuals working in 87 teams of 2 public organizations and 734 individuals working in 69 teams of a private organization, we tested and supported hypotheses that team leader positive affective presence was positively related to team information sharing, whereas team leader negative affective presence was negatively related to the same team process. In turn, team information sharing was positively related to team innovation, mediating the effects of leader affective presence on this team output. The results indicate the value of adopting an interpersonal individual differences approach to understanding how affect-related characteristics of leaders influence interaction processes and complex performance in teams. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  20. Microscale ion trap mass spectrometer (United States)

    Ramsey, J. Michael; Witten, William B.; Kornienko, Oleg


    An ion trap for mass spectrometric chemical analysis of ions is delineated. The ion trap includes a central electrode having an aperture; a pair of insulators, each having an aperture; a pair of end cap electrodes, each having an aperture; a first electronic signal source coupled to the central electrode; a second electronic signal source coupled to the end cap electrodes. The central electrode, insulators, and end cap electrodes are united in a sandwich construction where their respective apertures are coaxially aligned and symmetric about an axis to form a partially enclosed cavity having an effective radius r.sub.0 and an effective length 2z.sub.0, wherein r.sub.0 and/or z.sub.0 are less than 1.0 mm, and a ratio z.sub.0 /r.sub.0 is greater than 0.83.

  1. Centrifugal trapping in the magnetotail

    Directory of Open Access Journals (Sweden)

    D. C. Delcourt


    Full Text Available Particles leaving the neutral sheet in the distant magnetotail at times display adiabatic trajectory sequences characterized by an inflection toward the equator and subsequent mirroring in its vicinity. We demonstrate that this low-latitude mirroring results primarily from a centrifugal deceleration due to the fast direction-changing E×B drift. This effect which we refer to as "centrifugal trapping" appears both in guiding centre and full particle treatments. It thus does not directly relate to nonadiabatic motion. However, pitch angle scattering due to nonadiabatic neutral sheet interaction does play a role in reducing the parallel speed of the particles. We show that centrifugal trapping is an important mechanism for the confinement of the slowest (typically below the equatorial E×B drift speed plasma sheet populations to the midplane vicinity.

  2. Leaders who create change and those who manage it. How leaders limit success. (United States)

    Bruhn, John G


    There is no formula for either leading or managing change. Every organization and leader is unique. Leading change, however, is more art than science. Managing change is more science than art. Leading change is not simply a matter of a leader's style or personality; it is a leader's philosophy of how to generate and mobilize the total resources of an organization to enable it to be its best. Managing change, on the other hand, is focused on maintaining stability in an organization and containing the effects of unwanted and unexpected change. Leaders set the limits of success in their organizations by how they manage change. The different approaches of 2 leaders who have created change to correct problems in our health care delivery system are discussed.

  3. The Epithelial Sodium Channel α subunit (α ENaC alternatively spliced form "b" in Dahl rats: What's next?

    Directory of Open Access Journals (Sweden)

    Shehata Marlene F


    Full Text Available Abstract Background The amiloride-sensitive Epithelial Sodium Channel (ENaC is critical in maintaining Na+ balance, extracellular fluid volume and long term blood pressure control. ENaC is composed of three main subunits α, β, & γ. While α ENaC is critical for channel functionality, β & γ ENaC maximize channel function. To date, there are four alternatively spliced forms of the α subunit of ENaC (α ENaC-a, -b, -c, & -d that have been published in rats, in addition to the major α ENaC transcript. While α ENaC-a, -c & -d transcripts are low abundance transcripts compared to full-length α ENaC, α ENaC-b is a higher abundance and salt-sensitive transcript compared to full-length α ENaC. Presentation of the hypothesis α ENaC-b protein, which is preferentially produced in Dahl R rats, to a greater extent on high salt diet, exerts a dominant negative effect on full-length α ENaC subunit by physically binding to and trapping full-length α ENaC subunit in the endoplasmic reticulum, and finally accelerating full-length α ENaC proteolytic degradation in a dose-dependent manner. Testing the hypothesis 1 To examine the mRNA and protein abundance of α ENaC-b relative to α ENaC full-length in kidney, lung, and taste tissues of Dahl rats. 2 To compare the expression (mRNA and protein of α ENaC-b in kidneys of Dahl S and R rats on regular and high salt diet. 3 To examine the putative binding of α ENaC-b proteins to full-length α ENaC in vitro and to determine the impact of such binding on full-length α ENaC expression in vitro. Implications of the hypothesis Our studies will be the first to demonstrate the over-expression of salt-sensitive α ENaC-b spliced form in kidney tissues of Dahl R rats at the expense of full-length α ENaC. The current proposal will provide highly novel insights into the putative mechanisms leading to ENaC hypoactivity in high-salt-fed Dahl R rats. Finally, findings from the present proposal will uncover a new

  4. Poverty Traps and Climate Change


    Tol, Richard S. J.


    PUBLISHED We use a demo-economic model to examine the question of whether climate change could widen or deepen poverty traps. The model includes two crucial mechanisms. Parents are risk averse when deciding how many children to have; fertility is high when infant survival is low. High fertility spreads scarce household resources thin, resulting in children being poorly educated. At the macro level, technological progress is slow because of decreasing returns to scale in agriculture. With h...

  5. Unusual intron conservation near tissue-regulated exons found by splicing microarrays.

    Directory of Open Access Journals (Sweden)

    Charles W Sugnet


    Full Text Available Alternative splicing contributes to both gene regulation and protein diversity. To discover broad relationships between regulation of alternative splicing and sequence conservation, we applied a systems approach, using oligonucleotide microarrays designed to capture splicing information across the mouse genome. In a set of 22 adult tissues, we observe differential expression of RNA containing at least two alternative splice junctions for about 40% of the 6,216 alternative events we could detect. Statistical comparisons identify 171 cassette exons whose inclusion or skipping is different in brain relative to other tissues and another 28 exons whose splicing is different in muscle. A subset of these exons is associated with unusual blocks of intron sequence whose conservation in vertebrates rivals that of protein-coding exons. By focusing on sets of exons with similar regulatory patterns, we have identified new sequence motifs implicated in brain and muscle splicing regulation. Of note is a motif that is strikingly similar to the branchpoint consensus but is located downstream of the 5' splice site of exons included in muscle. Analysis of three paralogous membrane-associated guanylate kinase genes reveals that each contains a paralogous tissue-regulated exon with a similar tissue inclusion pattern. While the intron sequences flanking these exons remain highly conserved among mammalian orthologs, the paralogous flanking intron sequences have diverged considerably, suggesting unusually complex evolution of the regulation of alternative splicing in multigene families.

  6. Identification of a novel function of CX-4945 as a splicing regulator.

    Directory of Open Access Journals (Sweden)

    Hyeongki Kim

    Full Text Available Alternative splicing is a nearly ubiquitous versatile process that controls gene expression and creates numerous protein isoforms with different functions from a single gene. The significance of alternative splicing has been confirmed by the increasing number of human diseases that are caused by misregulation of splicing events. Very few compounds, however, have been reported to act as inhibitors of alternative splicing, and their potential clinical use needs to be evaluated. Here, we report that CX-4945, a previously well-characterized inhibitor of casein kinase 2 (CK2 and a molecule currently in clinical trials (Phase II for cancer treatment, regulates splicing in mammalian cells in a CK2-independent manner. Transcriptome-wide analysis using exon array also showed a widespread alteration in alternative splicing of numerous genes. We found that CX-4945 potently inhibits the Cdc2-like kinases (Clks in vitro and in turn, leads to suppression of the phosphorylation of serine/arginine-rich (SR proteins in mammalian cells. Surprisingly, the overall efficacy of CX-4945 on Clks (IC50 = 3-90 nM was stronger than that of TG-003, the strongest inhibitor reported to date. Of the Clks, Clk2 was most strongly inhibited by CX-4945 in an ATP-competitive manner. Our research revealed an unexpected activity of the drug candidate CX-4945 as a potent splicing modulator and also suggested a potential application for therapy of diseases caused by abnormal splicing.

  7. Functional diversity of human protein kinase splice variants marks significant expansion of human kinome

    Directory of Open Access Journals (Sweden)

    Anamika Krishanpal


    Full Text Available Abstract Background Protein kinases are involved in diverse spectrum of cellular processes. Availability of draft version of the human genomic data in the year 2001 enabled recognition of repertoire of protein kinases. However, over the years the human genomic data is being refined and the current release of human genomic data has helped us to recognize a larger repertoire of over 900 human protein kinases represented mainly by splice variants. Results Many of these identified protein kinases are alternatively spliced products. Interestingly, some of the human kinase splice variants appear to be significantly diverged in terms of their functional properties as represented by incorporation or absence of one or more domains. Many sets of protein kinase splice variants have substantially different domain organization and in a few sets of splice variants kinase domains belong to different subfamilies of kinases suggesting potential participation in different signal transduction pathways. Conclusions Addition or deletion of a domain between splice variants of multi-domain kinases appears to be a means of generating differences in the functional features of otherwise similar kinases. It is intriguing that marked sequence diversity within the catalytic regions of some of the splice variant kinases result in kinases belonging to different subfamilies. These human kinase splice variants with different functions might contribute to diversity of eukaryotic cellular signaling.

  8. Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, Enrique, E-mail: [Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Nicolas Cabrera, 1 Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Castello, Alfredo; Carrasco, Luis; Izquierdo, Jose M. [Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Nicolas Cabrera, 1 Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain)


    Highlights: {yields} Novel role for poliovirus 2A protease as splicing modulator. {yields} Poliovirus 2A protease inhibits the alternative splicing of pre-mRNAs. {yields} Poliovirus 2A protease blocks the second catalytic step of splicing. -- Abstract: Viruses have developed multiple strategies to interfere with the gene expression of host cells at different stages to ensure their own survival. Here we report a new role for poliovirus 2A{sup pro} modulating the alternative splicing of pre-mRNAs. Expression of 2A{sup pro} potently inhibits splicing of reporter genes in HeLa cells. Low amounts of 2A{sup pro} abrogate Fas exon 6 skipping, whereas higher levels of protease fully abolish Fas and FGFR2 splicing. In vitro splicing of MINX mRNA using nuclear extracts is also strongly inhibited by 2A{sup pro}, leading to accumulation of the first exon and the lariat product containing the unspliced second exon. These findings reveal that the mechanism of action of 2A{sup pro} on splicing is to selectively block the second catalytic step.

  9. Alternative splicing in colon, bladder, and prostate cancer identified by exon-array analysis

    DEFF Research Database (Denmark)

    Thorsen, Kasper; Sørensen, Karina D.; Brems-Eskildsen, Anne Sofie


    , PIK4CB, TPM1, and VCL). The validated tumor-specific splicing alterations were highly consistent, enabling clear separation of normal and cancer samples and in some cases even of different tumor stages. A subset of the tumor-specific splicing alterations (ACTN1, CALD1, and VCL) was found in all three...

  10. Reprogramming the Dynamin 2 mRNA by Spliceosome-mediated RNA Trans-splicing

    Directory of Open Access Journals (Sweden)

    Delphine Trochet


    Full Text Available Dynamin 2 (DNM2 is a large GTPase, ubiquitously expressed, involved in membrane trafficking and regulation of actin and microtubule cytoskeletons. DNM2 mutations cause autosomal dominant centronuclear myopathy which is a rare congenital myopathy characterized by skeletal muscle weakness and histopathological features including nuclear centralization in absence of regeneration. No curative treatment is currently available for the DNM2-related autosomal dominant centronuclear myopathy. In order to develop therapeutic strategy, we evaluated here the potential of Spliceosome-Mediated RNA Trans-splicing technology to reprogram the Dnm2-mRNA in vitro and in vivo in mice. We show that classical 3′-trans-splicing strategy cannot be considered as accurate therapeutic strategy regarding toxicity of the pre-trans-splicing molecules leading to low rate of trans-splicing in vivo. Thus, we tested alternative strategies devoted to prevent this toxicity and enhance frequency of trans-splicing events. We succeeded to overcome the toxicity through a 5′-trans-splicing strategy which also allows detection of trans-splicing events at mRNA and protein levels in vitro and in vivo. These results suggest that the Spliceosome-Mediated RNA Trans-splicing strategy may be used to reprogram mutated Dnm2-mRNA but highlight the potential toxicity linked to the molecular tools which have to be carefully investigated during preclinical development.

  11. Features of 5'-splice-site efficiency derived from disease-causing mutations and comparative genomics

    DEFF Research Database (Denmark)

    Roca, Xavier; Olson, Andrew J; Rao, Atmakuri R


    Many human diseases, including Fanconi anemia, hemophilia B, neurofibromatosis, and phenylketonuria, can be caused by 5'-splice-site (5'ss) mutations that are not predicted to disrupt splicing, according to position weight matrices. By using comparative genomics, we identify pairwise dependencies...

  12. Conservation and sex-specific splicing of the doublesex gene in the ...

    Indian Academy of Sciences (India)

    Genetic control of sex determination in insects has been best characterized in Drosophila melanogaster, where the master gene Sxl codes for RNA that is sex specifically spliced to produce a functional protein only in females. SXL regulates the sex-specific splicing of transformer (tra) RNA which, in turn, regulates the ...

  13. Differential dynamics of splicing factor SC35 during the cell cycle

    Indian Academy of Sciences (India)


    We analysed the dynamics of the splicing factor SC35 in interphase and mitotic cells. In HeLa cells expressing green fluorescent protein (GFP)-SC35, this was localized ... Cell cycle dynamics; FRAP analysis; mitotic interchromatin granules; splicing factor SC35 .... for 1 h at room temperature for single labelling experiments.

  14. Splicing-Mediated Autoregulation Modulates Rpl22p Expression in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Jason Gabunilas


    Full Text Available In Saccharomyces cerevisiae, splicing is critical for expression of ribosomal protein genes (RPGs, which are among the most highly expressed genes and are tightly regulated according to growth and environmental conditions. However, knowledge of the precise mechanisms by which RPG pre-mRNA splicing is regulated on a gene-by-gene basis is lacking. Here we show that Rpl22p has an extraribosomal role in the inhibition of splicing of the RPL22B pre-mRNA transcript. A stem loop secondary structure within the intron is necessary for pre-mRNA binding by Rpl22p in vivo and splicing inhibition in vivo and in vitro and can rescue splicing inhibition in vitro when added in trans to splicing reactions. Splicing inhibition by Rpl22p may be partly attributed to the reduction of co-transcriptional U1 snRNP recruitment to the pre-mRNA at the RPL22B locus. We further demonstrate that the inhibition of RPL22B pre-mRNA splicing contributes to the down-regulation of mature transcript during specific stress conditions, and provide evidence hinting at a regulatory role for this mechanism in conditions of suppressed ribosome biogenesis. These results demonstrate an autoregulatory mechanism that fine-tunes the expression of the Rpl22 protein and by extension Rpl22p paralog composition according to the cellular demands for ribosome biogenesis.

  15. Splicing-Mediated Autoregulation Modulates Rpl22p Expression in Saccharomyces cerevisiae. (United States)

    Gabunilas, Jason; Chanfreau, Guillaume


    In Saccharomyces cerevisiae, splicing is critical for expression of ribosomal protein genes (RPGs), which are among the most highly expressed genes and are tightly regulated according to growth and environmental conditions. However, knowledge of the precise mechanisms by which RPG pre-mRNA splicing is regulated on a gene-by-gene basis is lacking. Here we show that Rpl22p has an extraribosomal role in the inhibition of splicing of the RPL22B pre-mRNA transcript. A stem loop secondary structure within the intron is necessary for pre-mRNA binding by Rpl22p in vivo and splicing inhibition in vivo and in vitro and can rescue splicing inhibition in vitro when added in trans to splicing reactions. Splicing inhibition by Rpl22p may be partly attributed to the reduction of co-transcriptional U1 snRNP recruitment to the pre-mRNA at the RPL22B locus. We further demonstrate that the inhibition of RPL22B pre-mRNA splicing contributes to the down-regulation of mature transcript during specific stress conditions, and provide evidence hinting at a regulatory role for this mechanism in conditions of suppressed ribosome biogenesis. These results demonstrate an autoregulatory mechanism that fine-tunes the expression of the Rpl22 protein and by extension Rpl22p paralog composition according to the cellular demands for ribosome biogenesis.

  16. Effect of tension lap splice on the behavior of high strength concrete (HSC beams

    Directory of Open Access Journals (Sweden)

    Ahmed El-Azab


    Full Text Available In the recent years, many research efforts have been carried out on the bond strength between normal strength concrete (NSC and reinforcing bars spliced in tension zones in beams. Many codes gave a minimum splice length for tension and compression reinforcement as a factor of the bar diameter depending on many parameters such as concrete strength, steel yield stress, shape of bar end, shape of bar surface and also bar location. Also, codes gave another restriction about the percentage of total reinforcement to be spliced at the same time. Comparatively limited attention has been directed toward the bond between high strength concrete (HSC and reinforcing bars spliced in tension zones in beams. HSC has high modulus of elasticity, high density and long-term durability. This research presents an experimental study on the bond between high strength concrete (HSC and reinforcing bars spliced in tension zones in beams. It reports the influence of several parameters on bond in splices. The parameters covered are casting position, splice length as a factor of bar diameter, bar diameter and reinforcement ratio. The research involved tests on sixteen simply-supported beams of 1800 mm span, 200 mm width and 400 mm thickness made of HSC. In each beam, the total tensile steel bars were spliced in the constant moment zone. Crack pattern, crack propagation, cracking load, failure load and mi span deflection were recorded and analyzed to study the mentioned parameters effect.

  17. Measurement of Resistance and Strength of Conductor Splices in the MICE Coupling Magnets

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Feng Yu; Pan, Heng; Wu, Hong; Lui, X. K.; Li, E.; Dietderich, Dan; Higley, Hugh; Tam, D. G.; Trillaud, Fredric; Wang, Li; Green, M.A.


    The superconducting magnets for the Muon Ionization Cooling Experiment [1] (MICE) use a copper based Nb-Ti conductor with un-insulated dimensions of 0.95 by 1.60 mm. There may be as many as twelve splices in one MICE superconducting coupling coil. These splices are to be wound in the coil. The conductor splices produce Joule heating, which may cause the magnet to quench. A technique of making conductor splices was developed by ICST. Two types of 1-meter long of soldered lap-joints have been tested. Side-by-side splices and up-down one splices were studied theoretically and experimentally using two types of soft solder made of eutectic tin-lead solder and tin-silver solder. The resistances of the splices made by ICST were tested at LBNL at liquid helium temperatures over a range of magnetic fields up to 5 T. The breaking strength of 250 mm long splices was also measured at room temperature and liquid nitrogen temperature.

  18. Intrasplicing coordinates alternative first exons with alternative splicing in the protein 4.1R gene

    Energy Technology Data Exchange (ETDEWEB)

    Conboy, John G.; Parra, Marilyn K.; Tan, Jeff S.; Mohandas, Narla; Conboy, John G.


    In the protein 4.1R gene, alternative first exons splice differentially to alternative 3' splice sites far downstream in exon 2'/2 (E2'/2). We describe a novel intrasplicing mechanism by which exon 1A (E1A) splices exclusively to the distal E2'/2 acceptor via two nested splicing reactions regulated by novel properties of exon 1B (E1B). E1B behaves as an exon in the first step, using its consensus 5' donor to splice to the proximal E2'/2 acceptor. A long region of downstream intron is excised, juxtaposing E1B with E2'/2 to generate a new composite acceptor containing the E1B branchpoint/pyrimidine tract and E2 distal 3' AG-dinucleotide. Next, the upstream E1A splices over E1B to this distal acceptor, excising the remaining intron plus E1B and E2' to form mature E1A/E2 product. We mapped branch points for both intrasplicing reactions and demonstrated that mutation of the E1B 5' splice site or branchpoint abrogates intrasplicing. In the 4.1R gene, intrasplicing ultimately determines N-terminal protein structure and function. More generally, intrasplicing represents a new mechanism whereby alternative promoters can be coordinated with downstream alternative splicing.

  19. Tissue-specific alternative splicing and expression of ATP1B2 gene

    African Journals Online (AJOL)



    May 15, 2012 ... provide some useful information for further studies into the function of the bovine ATP1B2 gene. Alternative splicing (AS) is recognized as the major contributor to protein diversity from limited gene pool. ATP1B2-AS2 was the splice of intron retention found from ATP1B2 in liver, kidney, muscle and.

  20. Effect of splice-site polymorphisms of the TMPRSS4, NPHP4 and ...

    Indian Academy of Sciences (India)


    structural changes in mRNA transcripts as a result of splice-site polymorphisms implies that they may be of biological significance in certain pathological conditions. ..... show the genomic structures of the normal (diagram “a”) and abnormal (diagram “b” and “c”) splicing forms. Inserted and deleted sequences are indicated ...

  1. Leader power and leader self-serving behavior: The role of effective leadership beliefs and performance information


    Rus, Diana; Van Knippenberg, Daan; Wisse, Barbara


    International audience; In this research we investigated the role played by leader power in determining leader self-serving behavior. Based on an integration of insights from research on the determinants of leader behavior and the power-approach theory, we hypothesized that with higher leader power leader self-serving behavior is determined more by internal states like effective leadership beliefs and less by external cues like performance information. We found support for this prediction acr...

  2. When is a leader considered as a good leader? Perceived impact on teammates’ confidence and social acceptance as key ingredients


    Fransen, Katrien; Vanbeselaere, Norbert; De Cuyper, Bert; Vande Broek, Gert; Boen, Filip


    Effective leadership is perceived as a key factor for optimal team functioning. The present study aimed to identify the characteristics of athlete leaders with respect to four different leadership roles (i.e., task leader, motivational leader, social leader, and external leader), while recognizing the surrounding team context. Furthermore, we aimed to identify the most decisive characteristics for a player’s perceived leadership quality on each of these leadership roles. An on-line survey was...

  3. Leader empowering behavior : how do trust and leader-subordinate congruence in personal need for structure influence a leader's motivation to empower?


    Hauger, Camilla; Randen, Siri


    An important part of understanding leader empowering behavior is to establish its determinants. By understanding its determinants, leaders can become aware of what may influence their behavior, both unconsciously and consciously. This study therefore explores leader empowering behavior in relation to such assumed determinants in order to test if they have an impact on exercising leader empowering behavior. Our chosen determinants for this study are related to empowerment in ...

  4. Self-splicing of a group IIC intron: 5? exon recognition and alternative 5? splicing events implicate the stem?loop motif of a transcriptional terminator


    Toor, Navtej; Robart, Aaron R.; Christianson, Joshua; Zimmerly, Steven


    Bacterial IIC introns are a newly recognized subclass of group II introns whose ribozyme properties have not been characterized in detail. IIC introns are typically located downstream of transcriptional terminator motifs (inverted repeat followed by T's) or other inverted repeats in bacterial genomes. Here we have characterized the self-splicing activity of a IIC intron, B.h.I1, from Bacillus halodurans. B.h.I1 self-splices in vitro through hydrolysis to produce linear intron, but interesting...

  5. cis-Acting and trans-acting modulation of equine infectious anemia virus alternative RNA splicing

    International Nuclear Information System (INIS)

    Liao, Huey-Jane; Baker, Carl C.; Princler, Gerald L.; Derse, David


    Equine infectious anemia virus (EIAV), a lentivirus distantly related to HIV-1, encodes regulatory proteins, EIAV Tat (ETat) and Rev (ERev), from a four-exon mRNA. Exon 3 of the tat/rev mRNA contains a 30-nucleotide purine-rich element (PRE) which binds both ERev and SF2/ASF, a member of the SR family of RNA splicing factors. To better understand the role of this element in the regulation of EIAV pre-mRNA splicing, we quantified the effects of mutation or deletion of the PRE on exon 3 splicing in vitro and on alternative splicing in vivo. We also determined the branch point elements upstream of exons 3 and 4. In vitro splicing of exon 3 to exon 4 was not affected by mutation of the PRE, and addition of purified SR proteins enhanced splicing independently of the PRE. In vitro splicing of exon 2 to exon 3 was dependent on the PRE; under conditions of excess SR proteins, either the PRE or the 5' splice site of exon 3 was sufficient to activate splicing. We applied isoform-specific primers in real-time RT-PCR reactions to quantitatively analyze alternative splicing in cells transfected with rev-minus EIAV provirus constructs. In the context of provirus with wild-type exon 3, greater than 80% of the viral mRNAs were multiply spliced, and of these, less than 1% excluded exon 3. Deletion of the PRE resulted in a decrease in the relative amount of multiply spliced mRNA to about 40% of the total and approximately 39% of the viral mRNA excluded exon 3. Ectopic expression of ERev caused a decrease in the relative amount of multiply spliced mRNA to approximately 50% of the total and increased mRNAs that excluded exon 3 to about 4%. Over-expression of SF2/ASF in cells transfected with wild-type provirus constructs inhibited splicing but did not significantly alter exon 3 skipping

  6. Positron trapping at dislocations in metals

    International Nuclear Information System (INIS)

    Bergersen, B.; McMullen, T.


    The trapping rate of positrons at dislocations in metals, and its temperature dependence, are calculated. Two different trapping processes, with the excess energy absorbed in either electron-hole pair formation or by phonon creation, are considered and the former is found to be the most important. An extension of the theory to include depletion of the positron density around the dislocations in a diffusion approximation is included. The trapping is found to be transition limited if the temperature is low or the trap potential shallow. At room temperature diffusion is important for deep traps. (author)

  7. Nonadiabatic transitions in electrostatically trapped ammonia molecules

    International Nuclear Information System (INIS)

    Kirste, Moritz; Schnell, Melanie; Meijer, Gerard; Sartakov, Boris G.


    Nonadiabatic transitions are known to be major loss channels for atoms in magnetic traps but have thus far not been experimentally reported upon for trapped molecules. We have observed and quantified losses due to nonadiabatic transitions for three isotopologues of ammonia in electrostatic traps by comparing the trapping times in traps with a zero and a nonzero electric field at the center. Nonadiabatic transitions are seen to dominate the overall loss rate even for the present samples that are at relatively high temperatures of 30 mK. It is anticipated that losses due to nonadiabatic transitions in electric fields are omnipresent in ongoing experiments on cold molecules.

  8. How to be a good academic leader. (United States)

    Detsky, Allan S


    Individuals who take on leadership positions in academic health science centers help facilitate the mission of those institutions. However, they are often chosen on the basis of success in the core activities in research, education and patient care rather than on the basis of demonstrated leadership and management skills. Indeed, most academic leaders in the past have "learned on the job." This commentary provides practical advice on how to be an effective leader on the basis of the author's experiences as a Division Head and Chief of Medicine. It covers six themes (vision, managerial style, knowledge, people skills, organizational orientation and personal development) and offers 21 specific suggestions, one for each year of the author's leadership. It is hoped that this experience-derived advice will help future leaders in academic medicine.

  9. The Quality Of Leader/Employee Relationship

    Directory of Open Access Journals (Sweden)

    F. J. Carstens


    Full Text Available This study set out to investigate what role the quality of the relationship between business leaders and their employees played in the performance of their business. The study compared the business performance of forty-five area managers in one of the major listed banks in South Africa with their specific leader/employee relationship profiles. The research approach was quantitative and of a correlational nature. The results indicate that although certain elements within the relationship between business leaders and employees indeed have an influence on business performance this alone was not a sufficient condition. The study suggested that the dimensions relating to vision, trust, accountability and decision- making have the strongest influence on business performance. Further research in this area is suggested.

  10. Characterizing leader sequences of CRISPR loci

    DEFF Research Database (Denmark)

    Alkhnbashi, Omer; Shah, Shiraz Ali; Garrett, Roger Antony


    The CRISPR-Cas system is an adaptive immune system in many archaea and bacteria, which provides resistance against invading genetic elements. The first phase of CRISPR-Cas immunity is called adaptation, in which small DNA fragments are excised from genetic elements and are inserted into a CRISPR...... array generally adjacent to its so called leader sequence at one end of the array. It has been shown that transcription initiation and adaptation signals of the CRISPR array are located within the leader. However, apart from promoters, there is very little knowledge of sequence or structural motifs...... sequences by focusing on the consensus repeat of the adjacent CRISPR array and weak upstream conservation signals. We applied our tool to the analysis of a comprehensive genomic database and identified several characteristic properties of leader sequences specific to archaea and bacteria, ranging from...

  11. The Role of Alternative Splicing in the Control of Immune Homeostasis and Cellular Differentiation. (United States)

    Yabas, Mehmet; Elliott, Hannah; Hoyne, Gerard F


    Alternative splicing of pre-mRNA helps to enhance the genetic diversity within mammalian cells by increasing the number of protein isoforms that can be generated from one gene product. This provides a great deal of flexibility to the host cell to alter protein function, but when dysregulation in splicing occurs this can have important impact on health and disease. Alternative splicing is widely used in the mammalian immune system to control the development and function of antigen specific lymphocytes. In this review we will examine the splicing of pre-mRNAs yielding key proteins in the immune system that regulate apoptosis, lymphocyte differentiation, activation and homeostasis, and discuss how defects in splicing can contribute to diseases. We will describe how disruption to trans-acting factors, such as heterogeneous nuclear ribonucleoproteins (hnRNPs), can impact on cell survival and differentiation in the immune system.

  12. Towards a Consolidation of LHC Superconducting Splices for 7 TeV Operation

    CERN Document Server

    Bertinelli, F; Fessia, P; Garion, C; Mathot, S; Perin, A; Scheuerlein, C; Sgobba, S; ten Kat, H; Tock, J P; Verweij, A; Willering, G


    Following the analysis of the September 2008 LHC incident, the assembly process and the quality assurance of the main 13 kA interconnection splices were improved, with new measurement and diagnostics methods introduced. During the 2008-2009 shutdown ~5% of these 10 000 splices were newly assembled with these improvements implemented, but essentially maintaining the original design. It is known today that a limiting factor towards 7 TeV operation is the normal conducting resistance of ~15% of the original main 13 kA interconnection splices, associated to the electrical continuity of the copper stabiliser. A “Splices Task Force” has been set up at CERN to evaluate the need for, develop and test design improvements and prepare the implementation of a consolidation campaign. Important issues of splice design, process choice, resources and time requirements are considered.

  13. An experimental investigation on contact compression lap splice in circular columns

    Directory of Open Access Journals (Sweden)

    Hamed S. Askar


    The objective of the present investigation is to study the influence of splice length, volume of transverse reinforcement and end bearing condition on the behavior of compression lap splice. The conducted investigation included experimental tests of nine circular columns under uniaxial compression loads. All spliced bars were in contact with each other and with constant concrete cover. Based on the experimental investigation and test results, concluding remarks have been drawn, based on which a design simplified equation for splice length in compression has been developed. A correlation between the experimental and calculated results of the author specimens and other results available in literature, showed a good agreement. Also, the formulas adapted by different codes for predicting the compression lap splice length have been checked with the proposed equation.

  14. Fractional Differential Texture Descriptors Based on the Machado Entropy for Image Splicing Detection

    Directory of Open Access Journals (Sweden)

    Rabha W. Ibrahim


    Full Text Available Image splicing is a common operation in image forgery. Different techniques of image splicing detection have been utilized to regain people’s trust. This study introduces a texture enhancement technique involving the use of fractional differential masks based on the Machado entropy. The masks slide over the tampered image, and each pixel of the tampered image is convolved with the fractional mask weight window on eight directions. Consequently, the fractional differential texture descriptors are extracted using the gray-level co-occurrence matrix for image splicing detection. The support vector machine is used as a classifier that distinguishes between authentic and spliced images. Results prove that the achieved improvements of the proposed algorithm are compatible with other splicing detection methods.

  15. Controlled synthesis of target strings in a class of splicing systems. (United States)

    Chen, Peter C Y


    This article presents an approach for synthesizing target strings in a class of computational models of DNA recombination. The computational models are formalized as splicing systems in the context of formal languages. Given a splicing system (of a restricted type) and a target string to be synthesized, we construct (i) a rule-embedded splicing automaton that recognizes languages containing strings embedded with symbols representing splicing rules, and (ii) an automaton that implicitly recognizes the target string. By manipulating these two automata, we extract all rule sequences that lead to the production of the target string (if that string belongs to the splicing language). An algorithm for synthesizing a certain type of target strings based on such rule sequences is presented.

  16. Genetic variations and alternative splicing. The Glioma associated oncogene 1, GLI1.

    Directory of Open Access Journals (Sweden)

    Peter eZaphiropoulos


    Full Text Available Alternative splicing is a post-transcriptional regulatory process that is attaining stronger recognition as a modulator of gene expression. Alternative splicing occurs when the primary RNA transcript is differentially processed into more than one mature RNAs. This is the result of a variable definition/inclusion of the exons, the sequences that are excised from the primary RNA to form the mature RNAs. Consequently, RNA expression can generate a collection of differentially spliced RNAs, which may distinctly influence subsequent biological events, such as protein synthesis or other biomolecular interactions. Still the mechanisms that control exon definition and exon inclusion are not fully clarified. This mini-review highlights advances in this field as well as the impact of single nucleotide polymorphisms in affecting splicing decisions. The Glioma associated oncogene 1, GLI1, is taken as an example in addressing the role of nucleotide substitutions for splicing regulation.

  17. Coding potential of the products of alternative splicing in human.

    KAUST Repository

    Leoni, Guido


    BACKGROUND: Analysis of the human genome has revealed that as much as an order of magnitude more of the genomic sequence is transcribed than accounted for by the predicted and characterized genes. A number of these transcripts are alternatively spliced forms of known protein coding genes; however, it is becoming clear that many of them do not necessarily correspond to a functional protein. RESULTS: In this study we analyze alternative splicing isoforms of human gene products that are unambiguously identified by mass spectrometry and compare their properties with those of isoforms of the same genes for which no peptide was found in publicly available mass spectrometry datasets. We analyze them in detail for the presence of uninterrupted functional domains, active sites as well as the plausibility of their predicted structure. We report how well each of these strategies and their combination can correctly identify translated isoforms and derive a lower limit for their specificity, that is, their ability to correctly identify non-translated products. CONCLUSIONS: The most effective strategy for correctly identifying translated products relies on the conservation of active sites, but it can only be applied to a small fraction of isoforms, while a reasonably high coverage, sensitivity and specificity can be achieved by analyzing the presence of non-truncated functional domains. Combining the latter with an assessment of the plausibility of the modeled structure of the isoform increases both coverage and specificity with a moderate cost in terms of sensitivity.

  18. Comparative cross-species alternative splicing in plants. (United States)

    Ner-Gaon, Hadas; Leviatan, Noam; Rubin, Eitan; Fluhr, Robert


    Alternative splicing (AS) can add significantly to genome complexity. Plants are thought to exhibit less AS than animals. An algorithm, based on expressed sequence tag (EST) pairs gapped alignment, was developed that takes advantage of the relatively small intron and exon size in plants and directly compares pairs of ESTs to search for AS. EST pairs gapped alignment was first evaluated in Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa), and tomato (Solanum lycopersicum) for which annotated genome sequence is available and was shown to accurately predict splicing events. The method was then applied to 11 plant species that include 17 cultivars for which enough ESTs are available. The results show a large, 3.7-fold difference in AS rates between plant species with Arabidopsis and rice in the lower range and lettuce (Lactuca sativa) and sorghum (Sorghum bicolor) in the upper range. Hence, compared to higher animals, plants show a much greater degree of variety in their AS rates and in some plant species the rates of animal and plant AS are comparable although the distribution of AS types may differ. In eudicots but not monocots, a correlation between genome size and AS rates was detected, implying that in eudicots the mechanisms that lead to larger genomes are a driving force for the evolution of AS.

  19. The five messages leaders must manage. (United States)

    Hamm, John


    If you want to know why so many organizations sink into chaos, look no further than their leaders' mouths. Over and over, leaders present grand, overarching-yet fuzzy-notions of where they think the company is going. They assume everyone shares their definitions of"vision;" "accountability," and "results". The result is often sloppy behavior and misalignment that can cost a company dearly. Effective communication is a leader's most critical tool for doing the essential job of leadership: inspiring the organization to take responsibility for creating a better future. Five topics wield extraordinary influence within a company: organizational structure and hierarchy, financial results, the leader's sense of his or her job, time management, and corporate culture. Properly defined, disseminated, and controlled, these topics give the leader opportunities for increased accountability and substantially better performance. For example, one CEO always keeps communications about hierarchy admirably brief and to the point. When he realized he needed to realign internal resources, he told the staff: "I'm changing the structure of resources so that we can execute more effectively." After unveiling a new organization chart, he said, "It's 10:45. You have until noon to be annoyed, should that be your reaction. At noon, pizza will be served. At one o'clock, we go to work in our new positions." The most effective leaders ask themselves, "What needs to happen today to get where we want to go? What vague belief or notion can I clarify or debunk?" A CEO who communicates precisely to ten direct reports, each of whom communicates with equal precision to 40 other employees, aligns the organization's commitment and energy with a well-understood vision of the firm's real goals and opportunities.

  20. Intrinsic electron trapping in amorphous oxide (United States)

    Strand, Jack; Kaviani, Moloud; Afanas’ev, Valeri V.; Lisoni, Judit G.; Shluger, Alexander L.


    We demonstrate that electron trapping at intrinsic precursor sites is endemic in non-glass-forming amorphous oxide films. The energy distributions of trapped electron states in ultra-pure prototype amorphous (a)-HfO2 insulator obtained from exhaustive photo-depopulation experiments demonstrate electron states in the energy range of 2–3 eV below the oxide conduction band. These energy distributions are compared to the results of density functional calculations of a-HfO2 models of realistic density. The experimental results can be explained by the presence of intrinsic charge trapping sites formed by under-coordinated Hf cations and elongated Hf–O bonds in a-HfO2. These charge trapping states can capture up to two electrons, forming polarons and bi-polarons. The corresponding trapping sites are different from the dangling-bond type defects responsible for trapping in glass-forming oxides, such as SiO2, in that the traps are formed without bonds being broken. Furthermore, introduction of hydrogen causes formation of somewhat energetically deeper electron traps when a proton is immobilized next to the trapped electron bi-polaron. The proposed novel mechanism of intrinsic charge trapping in a-HfO2 represents a new paradigm for charge trapping in a broad class of non-glass-forming amorphous insulators.

  1. Algae commensal community in Genlisea traps

    Directory of Open Access Journals (Sweden)

    Konrad Wołowski


    Full Text Available The community of algae occurring in Genlisea traps and on the external traps surface in laboratory conditions were studied. A total of 29 taxa were found inside the traps, with abundant diatoms, green algae (Chlamydophyceae and four morphotypes of chrysophytes stomatocysts. One morphotype is described as new for science. There are two ways of algae getting into Genlisea traps. The majority of those recorded inside the traps, are mobile; swimming freely by flagella or moving exuding mucilage like diatoms being ablate to colonize the traps themselves. Another possibility is transport of algae by invertebrates such as mites and crustaceans. In any case algae in the Genlisea traps come from the surrounding environment. Two dominant groups of algae (Chladymonas div. and diatoms in the trap environment, show ability to hydrolyze phosphomonoseters. We suggest that algae in carnivorous plant traps can compete with plant (host for organic phosphate (phosphomonoseters. From the spectrum and ecological requirements of algal species found in the traps, environment inside the traps seems to be acidic. However, further studies are needed to test the relations between algae and carnivorous plants both in laboratory conditions and in the natural environment. All the reported taxa are described briefly and documented with 74 LM and SEM micrographs.

  2. Trapping Dust to Form Planets (United States)

    Kohler, Susanna


    Growing a planet from a dust grain is hard work! A new study explores how vortices in protoplanetary disks can assist this process.When Dust Growth FailsTop: ALMA image of the protoplanetary disk of V1247 Orionis, with different emission components labeled. Bottom: Synthetic image constructed from the best-fit model. [Kraus et al. 2017]Gradual accretion onto a seed particle seems like a reasonable way to grow a planet from a grain of dust; after all, planetary embryos orbit within dusty protoplanetary disks, which provides them with plenty of fuel to accrete so they can grow. Theres a challenge to this picture, though: the radial drift problem.The radial drift problem acknowledges that, as growing dust grains orbit within the disk, the drag force on them continues to grow as well. For large enough dust grains perhaps around 1 millimeter the drag force will cause the grains orbits to decay, and the particles drift into the star before they are able to grow into planetesimals and planets.A Close-Up Look with ALMASo how do we overcome the radial drift problem in order to form planets? A commonly proposed mechanism is dust trapping, in which long-lived vortices in the disk trap the dust particles, preventing them from falling inwards. This allows the particles to persist for millions of years long enough to grow beyond the radial drift barrier.Observationally, these dust-trapping vortices should have signatures: we would expect to see, at millimeter wavelengths, specific bright, asymmetric structures where the trapping occurs in protoplanetary disks. Such disk structures have been difficult to spot with past instrumentation, but the Atacama Large Millimeter/submillimeter Array (ALMA) has made some new observations of the disk V1247 Orionis that might be just what were looking for.Schematic of the authors model for the disk of V1247 Orionis. [Kraus et al. 2017]Trapped in a Vortex?ALMAs observations of V1247 Orionis are reported by a team of scientists led by Stefan

  3. The emergence of alternative 3' and 5' splice site exons from constitutive exons.

    Directory of Open Access Journals (Sweden)

    Eli Koren


    Full Text Available Alternative 3' and 5' splice site (ss events constitute a significant part of all alternative splicing events. These events were also found to be related to several aberrant splicing diseases. However, only few of the characteristics that distinguish these events from alternative cassette exons are known currently. In this study, we compared the characteristics of constitutive exons, alternative cassette exons, and alternative 3'ss and 5'ss exons. The results revealed that alternative 3'ss and 5'ss exons are an intermediate state between constitutive and alternative cassette exons, where the constitutive side resembles constitutive exons, and the alternative side resembles alternative cassette exons. The results also show that alternative 3'ss and 5'ss exons exhibit low levels of symmetry (frame-preserving, similar to constitutive exons, whereas the sequence between the two alternative splice sites shows high symmetry levels, similar to alternative cassette exons. In addition, flanking intronic conservation analysis revealed that exons whose alternative splice sites are at least nine nucleotides apart show a high conservation level, indicating intronic participation in the regulation of their splicing, whereas exons whose alternative splice sites are fewer than nine nucleotides apart show a low conservation level. Further examination of these exons, spanning seven vertebrate species, suggests an evolutionary model in which the alternative state is a derivative of an ancestral constitutive exon, where a mutation inside the exon or along the flanking intron resulted in the creation of a new splice site that competes with the original one, leading to alternative splice site selection. This model was validated experimentally on four exons, showing that they indeed originated from constitutive exons that acquired a new competing splice site during evolution.

  4. Splice Expression Variation Analysis (SEVA) for Inter-tumor Heterogeneity of Gene Isoform Usage in Cancer. (United States)

    Afsari, Bahman; Guo, Theresa; Considine, Michael; Florea, Liliana; Kagohara, Luciane T; Stein-O'Brien, Genevieve L; Kelley, Dylan; Flam, Emily; Zambo, Kristina D; Ha, Patrick K; Geman, Donald; Ochs, Michael F; Califano, Joseph A; Gaykalova, Daria A; Favorov, Alexander V; Fertig, Elana J


    Current bioinformatics methods to detect changes in gene isoform usage in distinct phenotypes compare the relative expected isoform usage in phenotypes. These statistics model differences in isoform usage in normal tissues, which have stable regulation of gene splicing. Pathological conditions, such as cancer, can have broken regulation of splicing that increases the heterogeneity of the expression of splice variants. Inferring events with such differential heterogeneity in gene isoform usage requires new statistical approaches. We introduce Splice Expression Variability Analysis (SEVA) to model increased heterogeneity of splice variant usage between conditions (e.g., tumor and normal samples). SEVA uses a rank-based multivariate statistic that compares the variability of junction expression profiles within one condition to the variability within another. Simulated data show that SEVA is unique in modeling heterogeneity of gene isoform usage, and benchmark SEVA's performance against EBSeq, DiffSplice, and rMATS that model differential isoform usage instead of heterogeneity. We confirm the accuracy of SEVA in identifying known splice variants in head and neck cancer and perform cross-study validation of novel splice variants. A novel comparison of splice variant heterogeneity between subtypes of head and neck cancer demonstrated unanticipated similarity between the heterogeneity of gene isoform usage in HPV-positive and HPV-negative subtypes and anticipated increased heterogeneity among HPV-negative samples with mutations in genes that regulate the splice variant machinery. These results show that SEVA accurately models differential heterogeneity of gene isoform usage from RNA-seq data. SEVA is implemented in the R/Bioconductor package GSReg., Supplementary data are available at Bioinformatics online. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please email:

  5. Translational profiling of B cells infected with the Epstein-Barr virus reveals 5' leader ribosome recruitment through upstream open reading frames. (United States)

    Bencun, Maja; Klinke, Olaf; Hotz-Wagenblatt, Agnes; Klaus, Severina; Tsai, Ming-Han; Poirey, Remy; Delecluse, Henri-Jacques


    The Epstein-Barr virus (EBV) genome encodes several hundred transcripts. We have used ribosome profiling to characterize viral translation in infected cells and map new translation initiation sites. We show here that EBV transcripts are translated with highly variable efficiency, owing to variable transcription and translation rates, variable ribosome recruitment to the leader region and coverage by monosomes versus polysomes. Some transcripts were hardly translated, others mainly carried monosomes, showed ribosome accumulation in leader regions and most likely represent non-coding RNAs. A similar process was visible for a subset of lytic genes including the key transactivators BZLF1 and BRLF1 in cells infected with weakly replicating EBV strains. This suggests that ribosome trapping, particularly in the leader region, represents a new checkpoint for the repression of lytic replication. We could identify 25 upstream open reading frames (uORFs) located upstream of coding transcripts that displayed 5' leader ribosome trapping, six of which were located in the leader region shared by many latent transcripts. These uORFs repressed viral translation and are likely to play an important role in the regulation of EBV translation.

  6. Leaders' mental health at work: Empirical, methodological, and policy directions. (United States)

    Barling, Julian; Cloutier, Anika


    While employees' mental health is the focus of considerable attention from researchers, the public, and policymakers, leaders' mental health has almost escaped attention. We start by considering several reasons for this, followed by discussions of the effects of leaders' mental health on their own leadership behaviors, the emotional toll of high-quality leadership, and interventions to enhance leaders' mental health. We offer 8 possible directions for future research on leaders' mental health. Finally, we discuss methodological obstacles encountered when investigating leaders' mental health, and policy dilemmas raised by leaders' mental health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  7. Alternative splicing and nonsense-mediated decay of circadian clock genes under environmental stress conditions in Arabidopsis. (United States)

    Kwon, Young-Ju; Park, Mi-Jeong; Kim, Sang-Gyu; Baldwin, Ian T; Park, Chung-Mo


    The circadian clock enables living organisms to anticipate recurring daily and seasonal fluctuations in their growth habitats and synchronize their biology to the environmental cycle. The plant circadian clock consists of multiple transcription-translation feedback loops that are entrained by environmental signals, such as light and temperature. In recent years, alternative splicing emerges as an important molecular mechanism that modulates the clock function in plants. Several clock genes are known to undergo alternative splicing in response to changes in environmental conditions, suggesting that the clock function is intimately associated with environmental responses via the alternative splicing of the clock genes. However, the alternative splicing events of the clock genes have not been studied at the molecular level. We systematically examined whether major clock genes undergo alternative splicing under various environmental conditions in Arabidopsis. We also investigated the fates of the RNA splice variants of the clock genes. It was found that the clock genes, including EARLY FLOWERING 3 (ELF3) and ZEITLUPE (ZTL) that have not been studied in terms of alternative splicing, undergo extensive alternative splicing through diverse modes of splicing events, such as intron retention, exon skipping, and selection of alternative 5' splice site. Their alternative splicing patterns were differentially influenced by changes in photoperiod, temperature extremes, and salt stress. Notably, the RNA splice variants of TIMING OF CAB EXPRESSION 1 (TOC1) and ELF3 were degraded through the nonsense-mediated decay (NMD) pathway, whereas those of other clock genes were insensitive to NMD. Taken together, our observations demonstrate that the major clock genes examined undergo extensive alternative splicing under various environmental conditions, suggesting that alternative splicing is a molecular scheme that underlies the linkage between the clock and environmental stress

  8. High-speed video observations of a natural negative stepped leader and subsequent dart-stepped leader (United States)

    Petersen, Danyal A.; Beasley, William H.


    present new high-speed video observations of a natural negative stepped leader and a subsequent negative dart-stepped leader. Observations were made at a distance of 770 m using a high-speed video camera at 10,000 frames per second, a microwave-frequency radio receiver, a broadband electric field antenna, and an avalanche photodiode array. Lightning leader breakdown was observed in detail for both the negative stepped leader and the subsequent dart-stepped leader. During the negative stepped leader breakdown, detailed images were captured of the discharge structures near the leader tips. These structures bear a remarkable resemblance to the corona streamer zone and space leader discharges that have been observed in laboratory-generated negative stepped leaders. During the dart-stepped leader breakdown, no corona streamer zone was observed outside of the decaying return stroke channel, but small luminous structures that are suggestive of space leaders were observed just ahead of the main dart leader tip. Two distinct low-luminosity zones were observed just ahead of the dart leader tip, suggestive of two distinct breakdown regimes. A multipath junction was observed in the main channel to ground following the first return stroke but was not observed following the second return stroke. Finally, microwave-frequency radio emissions for both leader types and their return strokes were recorded, and their time domain behavior is compared and discussed.

  9. The putative Leishmania telomerase RNA (LeishTER undergoes trans-splicing and contains a conserved template sequence.

    Directory of Open Access Journals (Sweden)

    Elton J R Vasconcelos

    Full Text Available Telomerase RNAs (TERs are highly divergent between species, varying in size and sequence composition. Here, we identify a candidate for the telomerase RNA component of Leishmania genus, which includes species that cause leishmaniasis, a neglected tropical disease. Merging a thorough computational screening combined with RNA-seq evidence, we mapped a non-coding RNA gene localized in a syntenic locus on chromosome 25 of five Leishmania species that shares partial synteny with both Trypanosoma brucei TER locus and a putative TER candidate-containing locus of Crithidia fasciculata. Using target-driven molecular biology approaches, we detected a ∼2,100 nt transcript (LeishTER that contains a 5' spliced leader (SL cap, a putative 3' polyA tail and a predicted C/D box snoRNA domain. LeishTER is expressed at similar levels in the logarithmic and stationary growth phases of promastigote forms. A 5'SL capped LeishTER co-immunoprecipitated and co-localized with the telomerase protein component (TERT in a cell cycle-dependent manner. Prediction of its secondary structure strongly suggests the existence of a bona fide single-stranded template sequence and a conserved C[U/C]GUCA motif-containing helix II, representing the template boundary element. This study paves the way for further investigations on the biogenesis of parasite TERT ribonucleoproteins (RNPs and its role in parasite telomere biology.

  10. Discriminating between antihydrogen and mirror-trapped antiprotons in a minimum-B trap

    CERN Document Server

    Amole, C; Ashkezari, M D; Baquero-Ruiz, M; Bertsche, W; Butler, E; Cesar, C L; Chapman, S; Charlton, M; Deller, A; Eriksson, S; Fajans, J; Friesen, T; Fujiwara, M C; Gill, D R; Gutierrez, A; Hangst, J S; Hardy, W N; Hayden, M E; Humphries, A J; Hydomako, R; Kurchaninov, L; Jonsell, S; Madsen, N; Menary, S; Nolan, P; Olchanski, K; Olin, A; Povilus, A; Pusa, P; Robicheaux, F; Sarid, E; Silveira, D M; So, C; Storey, J W; Thompson, R I; van der Werf, D P; Wurtele, J S


    Recently, antihydrogen atoms were trapped at CERN in a magnetic minimum (minimum-B) trap formed by superconducting octupole and mirror magnet coils. The trapped antiatoms were detected by rapidly turning off these magnets, thereby eliminating the magnetic minimum and releasing any antiatoms contained in the trap. Once released, these antiatoms quickly hit the trap wall, whereupon the positrons and antiprotons in the antiatoms annihilated. The antiproton annihilations produce easily detected signals; we used these signals to prove that we trapped antihydrogen. However, our technique could be confounded by mirror-trapped antiprotons, which would produce seemingly-identical annihilation signals upon hitting the trap wall. In this paper, we discuss possible sources of mirror-trapped antiprotons and show that antihydrogen and antiprotons can be readily distinguished, often with the aid of applied electric fields, by analyzing the annihilation locations and times. We further discuss the general properties of antipr...

  11. Portable Pbars, traps that travel

    International Nuclear Information System (INIS)

    Howe, S.D.; Hynes, M.V.; Picklesimer, A.


    The advent of antiproton research utilizing relatively small scale storage devices for very large numbers of these particles opens the possibility of transporting these devices to a research site removed from the accelerator center that produced the antiprotons. Such a portable source of antiprotons could open many new areas of research and make antiprotons available to a new research community. At present antiprotons are available at energies down to 1 MeV. From a portable source these particles can be made available at energies ranging from several tens of kilovolts down to a few millielectron volts. These low energies are in the domain of interest to the atomic and condensed matter physicist. In addition such a source can be used as an injector for an accelerator which could increase the energy domain even further. Moreover, the availability of such a source at a university will open research with antiprotons to a broader range of students than possible at a centralized research facility. This report focuses on the use of ion traps, in particular cylindrical traps, for the antiproton storage device. These devices store the charged antiprotons in a combination of electric and magnet fields. At high enough density and low enough temperature the charged cloud will be susceptible to plasma instabilities. Present day ion trap work is just starting to explore this domain. Our assessment of feasibility is based on what could be done with present day technology and what future technology could achieve. We conclude our report with a radiation safety study that shows that about 10 11 antiprotons can be transported safely, however the federal guidelines for this transport must be reviewed in detail. More antiprotons than this will require special transportation arrangements. 28 refs., 8 figs

  12. The composite insect trap: an innovative combination trap for biologically diverse sampling.

    Directory of Open Access Journals (Sweden)

    Laura Russo

    Full Text Available Documentation of insect diversity is an important component of the study of biodiversity, community dynamics, and global change. Accurate identification of insects usually requires catching individuals for close inspection. However, because insects are so diverse, most trapping methods are specifically tailored to a particular taxonomic group. For scientists interested in the broadest possible spectrum of insect taxa, whether for long term monitoring of an ecosystem or for a species inventory, the use of several different trapping methods is usually necessary. We describe a novel composite method for capturing a diverse spectrum of insect taxa. The Composite Insect Trap incorporates elements from four different existing trapping methods: the cone trap, malaise trap, pan trap, and flight intercept trap. It is affordable, resistant, easy to assemble and disassemble, and collects a wide variety of insect taxa. Here we describe the design, construction, and effectiveness of the Composite Insect Trap tested during a study of insect diversity. The trap catches a broad array of insects and can eliminate the need to use multiple trap types in biodiversity studies. We propose that the Composite Insect Trap is a useful addition to the trapping methods currently available to ecologists and will be extremely effective for monitoring community level dynamics, biodiversity assessment, and conservation and restoration work. In addition, the Composite Insect Trap will be of use to other insect specialists, such as taxonomists, that are interested in describing the insect taxa in a given area.

  13. Educating Preservice Media Specialists: Developing School Leaders. (United States)

    Vansickle, Sharon


    This study was conducted to determine how preservice media specialists perceive leadership responsibilities and certain tasks associated with the school library media profession. Results indicate that many viewed themselves as support personnel rather than school leaders, thus establishing the need to include leadership development courses in…

  14. Choosing a public-spirited leader

    DEFF Research Database (Denmark)

    Markussen, Thomas; Tyran, Jean-robert


    In this experiment, voters select a leader who can either act in the public interest, i.e. make efficient and equitable policy choices, or act in a corrupt way, i.e. use public funds for private gain. Voters can observe candidates⿿ pro-social behavior and their score in a cognitive ability test...

  15. Strategies for Teacher and School Leader Improvement

    Directory of Open Access Journals (Sweden)

    Colin Everett


    Full Text Available Book review of Supervision and Evaluation for Learning and Growth: Strategies for Teacher and School Leader Improvement. By Daniel R. Tomal, Robert K. Wilhite, Barbara J. Phillips, Paul A. Sims, and Nancy P. Gibson. Lanham, MD: Rowman and Littlefield, 2015.

  16. Identity talk of aspirational ethical leaders

    NARCIS (Netherlands)

    Koning, J.B.M.; Waistell, J.


    This study investigates how business leaders dynamically narrate their aspirational ethical leadership identities. In doing so, it furthers understanding of ethical leadership as a process situated in time and place. The analysis focuses on the discursive strategies used to narrate identity and

  17. The Emergent Power of Teacher Leaders (United States)

    Safir, Shane


    "Coming from complexity science, the term emergence describes the dynamic and unpredictable ways through which change unfolds in organizations," writes Shane Safir in this article about how teacher leaders can transform a school's climate and culture. Using Berkeley High School in California as an example, Safir explains how successful…

  18. Industry Leader Perceptions of Workplace Safety (United States)

    Dunlap, Erik Scott


    This study investigated the perceptions of workplace safety held by industry leaders who were near completion of a Master of Business Administration (MBA) degree. This was a qualitative study that utilized interpretivism as the theoretical framework. The study sought to answer four research questions. (1) How do participants conceptualize…

  19. Lived Experience of University Continuing Education Leaders (United States)

    Landry, Janice


    This article is based on a study that explored the professional lives of eight leaders of continuing education in Canadian universities, with a focus on their administrative role, to provide a deeper understanding of how they live within their practice (lived experience). A practical listing of 56 horizons of experience was identified, useful as…

  20. A Framing Primer for Community College Leaders (United States)

    Nausieda, Ryan


    The purpose of this article is to be a tool for community college leaders, as well as campus members, to positively and effectively utilize framing on their campuses. The fictional case of Maggie Pascal at Midwestern Community College illustrates the process of framing the change of a new partnership with Wind Energy Corporation to internal…

  1. Leaders as Linchpins for Framing Meaning (United States)

    Eddy, Pamela L.


    Community college leaders serve as linchpins for framing meaning on campus. The current pressures on institutions (given declining financial resources, demands for accountability, changing faculty ranks, and societal need for new knowledge) require presidents to juggle multiple priorities while presenting a cohesive message to campus constituents.…

  2. Outreach to Future Hispanic Educational Leaders. (United States)

    Serafin, Ana Gil

    This paper discusses issues related to the recruitment of Hispanic-American educational leaders, focusing on the El Centro de Recursos Educativos outreach center at Northeastern Illinois University in Chicago, which began operation in Fall 1997. It examines the characteristics of successful programs for Hispanic recruitment and retention and the…

  3. David Ben-Gurion: A Creative Leader (United States)

    Rosemarin, Shoshana


    David Ben-Gurion (1886-1973), the first Prime Minister of Israel, is included in Pasternak's (2001) list of the nine most memorable leaders of the twentieth century. All of them are remembered for the reforms they initiated. Roosevelt (USA), Stalin (Russia), Castro (Cuba), and Thatcher (England) focused on social-economical changes, whereas Gandhi…

  4. Strategic Thinking: The Untapped Resource for Leaders. (United States)

    Alfred, Richard L.


    Strategic thinking is an organized, analytical process by which college leaders can assess: (1) existing and potential competitors; (2) sources of competitive advantage; and (3) college capabilities and competitive position. Three outcomes of strategic thinking are: (1) clear institutional strategy and direction; (2) improved institutional…

  5. Lebanese Cherishing a Transformational Educational Leader (United States)

    Mattar, Dorine Maurice


    Purpose: The purpose of this paper is to find out if the characteristics, traits and leadership style of an effective university leader in Lebanon match those of a transformational one. Moreover, it is intended to shed light on the possible transferability of the transformational leadership's success to the Middle-Eastern society where norms and…

  6. The School Leader's Guide to Social Media (United States)

    Williamson, Ronald; Johnston, J. Howard


    Social media has exploded onto American culture--including our schools--giving educators a unique opportunity to shape this phenomenon into a powerful tool for improving educational leadership practices. With real-world examples and practical tips, this essential guide shows school leaders how to address both the potential benefits and common…

  7. Role Perceptions and Satisfaction with Leader Behavior. (United States)

    Creed, Philip J.; Enns, Frederick


    Reports on a study of the levels of personal and job satisfaction experienced by employees in the central office of a large urban school system as they responded to the leader behavior of their immediate superiors. The study tests aspects of propositions put forward in Path-Goal Theory. (Author/IRT)

  8. Constructive consequences of leaders' forcing influence styles

    NARCIS (Netherlands)

    Emans, B.J.M.; Munduate, L; Klaver, E; Van de Vliert, E.

    In contrast to non-forcing influence styles used by leaders, their forcing influence styles are commonly found to be ineffective, evoking sheer resistance, rather than compliance. As a corollary of conglomerate conflict behavior theory, we state that forcing, if combined with non-forcing, may

  9. Developing the Girl as a Leader (United States)

    Hembrow-Beach, Rose


    Single-sex educational environments can create young women who are engaged, active leaders. Girls receive differential treatment in combined-sex education environments. Girls often do not receive the encouragement or instruction to assume leadership. I want to identify the elements of single-sex education that foster female leadership and consider…

  10. Job Satisfaction of Secondary Content Area Leaders (United States)

    Roberts, Christine K.


    Educational researchers have examined both observed and perceived influences of the job satisfaction levels of secondary teachers and post-secondary department chairs. However, researchers have largely ignored a third group of educators: secondary Content Area Leaders (CALs). The overall satisfaction levels and the potentially influencing factors…

  11. Global Issues Confronting Student Affairs Leaders. (United States)

    Barlow, Allen R.


    An Australian student affairs leader summarizes issues discussed at recent international conferences. A significant number of commonalities appear in the information. These issues provide a global perspective on some of the problems and challenges facing student affairs. This international perspective has rarely been described in the literature…

  12. Principals' Collaborative Roles as Leaders for Learning (United States)

    Kitchen, Margaret; Gray, Susan; Jeurissen, Maree


    This article draws on data from three multicultural New Zealand primary schools to reconceptualize principals' roles as leaders for learning. In doing so, the writers build on Sinnema and Robinson's (2012) article on goal setting in principal evaluation. Sinnema and Robinson found that even principals hand-picked for their experience fell short on…

  13. The Future of Instructional Teacher Leader Roles (United States)

    Mangin, Melinda M.; Stoelinga, Sara Ray


    In response to increased performance expectations, schools and districts are turning to nonsupervisory, school-based, instructional teacher leader roles to help improve teachers' instruction and enhance student learning. Increased opportunities to learn about teacher leadership may facilitate the implementation and institutionalization of…

  14. Promoting leaders in labour research | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)


    Promoting leaders in labour research. July 30, 2015. Image. Education is essential to future opportunities. In several Asian countries with large youth bulges, investments in training will be needed to equip the next generation for work in more skill intensive sectors. IDRC. INSIGHT | INCLUSIVE GROWTH. Despite the ...

  15. Is the Army Developing Strategic Leaders? (United States)


    earn an MMAS. Completing the MMAS process required many late nights, weekends, and holidays spent in front of a computer or in the library, so I am...5,000,000 people in 5,000 talks and seminars throughout the US, Canada , and 55 other countries worldwide. As a keynote speaker and seminar leader, he

  16. Resilient Women Leaders: A Qualitative Investigation (United States)

    Baldwin, Julia; Maldonado, Nancy L.; Lacey, Candace H.; Efinger, Joan


    This qualitative study investigated perceptions of resilient, transformational, successful women leaders regarding their own resiliency and leadership. The ten participants provided information during semi-structured, open-ended, audio taped interviews which were transcribed, hand coded, and then analyzed with QSR N6 software. Findings indicated…

  17. Solar Trap for Banana Drying Method

    Directory of Open Access Journals (Sweden)

    Musa S.


    Full Text Available Food drying methods nowadays are mostly in high use of electricity and fuel which lead to high operational cost. This has resulted in a waste of energy and money due to the use of modern tools requires significant costs for implementation. Meanwhile, the traditional food drying process only uses sun rays in their process, where the process is far more efficient than the modern drying method. In this study, the test was conducted to determine the trapped solar heat energy requirements for the process of drying foods such as agricultural products, particularly bananas. The solar trap test by using solar trap container was carried out include determining the thermal energy requirement for drying, preparing equipment (solar trap container to trap solar energy, handling and drying tests on samples of bananas. The percentage amount of water removal and energy required for the drying process was found to be 48% and 134 J. The results of this study can determine that solar trap drying method is easier, quicker and more effective than the usual method of drying because it use natural solar energy. Several proposals have been suggested for improvement for future study, such as controlling the solar trap air in the container, replacing the trap solar wall with a darker color, examining the floors slope so that more solar traps collected and installing a small hose on the base of the container so that the water evaporated in the solar trap may exit through the route.

  18. Trapping leidenfrost drops with crenelations. (United States)

    Dupeux, Guillaume; Le Merrer, Marie; Clanet, Christophe; Quéré, David


    Drops placed on very hot solids levitate on a cushion of their own vapor, as discovered by Leidenfrost. This confers to these drops a remarkable mobility, which makes problematic their control and manipulation. Here we show how crenelated surfaces can be used to increase the friction of Leidenfrost drops by a factor on the order of 100, making them decelerate and be trapped on centimetric distances instead of the usual metric ones. We measure and characterize the friction force as a function of the design of the crenelations.

  19. Bose condensation in (random traps

    Directory of Open Access Journals (Sweden)

    V.A. Zagrebnov


    Full Text Available We study a non-interacting (perfect Bose-gas in random external potentials (traps. It is shown that a generalized Bose-Einstein condensation in the random eigenstates manifests if and only if the same occurs in the one-particle kinetic-energy eigenstates, which corresponds to the generalized condensation of the free Bose-gas. Moreover, we prove that the amounts of both condensate densities are equal. This statement is relevant for justification of the Bogoliubov approximation} in the theory of disordered boson systems.

  20. Opinion leaders and changes over time: a survey. (United States)

    Doumit, Gaby; Wright, Frances C; Graham, Ian D; Smith, Andrew; Grimshaw, Jeremy


    Opinion leaders represent one way to disseminate new knowledge and influence the practice behaviors of physicians. This study explored the stability of opinion leaders over time, whether opinion leaders were polymorphic (i.e., influencing multiple practice areas) or monomorphic (i.e., influencing one practice area), and reach of opinion leaders in their local network. We surveyed surgeons and pathologists in Ontario to identify opinion leaders for colorectal cancer in 2003 and 2005 and to identify opinion leaders for breast cancer in 2005. We explored whether opinion leaders for colorectal cancer identified in 2003 were re-identified in 2005. We examined whether opinion leaders were considered polymorphic (nominated in 2005 as opinion leaders for both colorectal and breast cancer) or monomorphic (nominated in 2005 for only one condition). Social-network mapping was used to identify the number of local colleagues identifying opinion leaders. Response rates for surgeons were 41% (2003) and 40% (2005); response rates for pathologists were 42% (2003) and 37% (2005). Four (25%) of the surgical opinion leaders identified in 2003 for colorectal cancer were re-identified in 2005. No pathology opinion leaders for colorectal cancer were identified in both 2003 and 2005. Only 29% of surgical opinion leaders and 17% of pathology opinion leaders identified in the 2005 survey were considered influential for both colorectal cancer and breast cancer. Social-network mapping revealed that only a limited number of general surgeons (12%) or pathologists (7%) were connected to the social networks of identified opinion leaders. Opinion leaders identified in this study were not stable over a two-year time period and generally appear to be monomorphic, with clearly demarcated areas of expertise and limited spheres of influence. These findings may limit the practicability of routinely using opinion leaders to influence practice.

  1. Characteristics of successful aviation leaders of Oklahoma (United States)

    Kutz, Mary N. Hill

    Scope and method of study. The purpose of the study was to examine the personal traits, skills, practices, behaviors, background, academic, and career success patterns of selected aviation leaders in Oklahoma. A purposive sample of 18 leaders who had achieved a top-ranked position of aviation leadership in an organization or a position of influence in the community was selected for interview. The leaders chosen for interview came from a variety of aviation organizations including government, academia, military, corporate aviation, and air carrier leadership as well as community leadership (specifically those aviation personnel who were engaged in a political or civic leadership role). Findings and conclusions. This study identified no common career choices, educational, family, or other background factors exclusively responsible for leadership success of all of the participants. Some of the more significant findings were that a high percentage of the leaders held undergraduate and advanced degrees; however, success had been achieved by some who had little or no college education. Aviation technical experience was not a prerequisite for aviation leadership success in that a significant number of the participants held no airman rating and some had entered positions of aviation leadership from non-aviation related careers. All had received some positive learning experience from their family background even those backgrounds which were less than desirable. All of the participants had been involved in volunteer civic or humanitarian leadership roles, and all had received numerous honors. The most frequently identified value expressed by the leaders was honesty; the predominant management style was participative with a strong backup style for directing, the most important skills were communication and listening skills, and the most frequently mentioned characteristics of success were honesty, credibility, vision, high standards, love for aviation and fiscal

  2. Athletic Training Clinical Instructors as Situational Leaders. (United States)

    Meyer, Linda Platt


    OBJECTIVE: To present Situational Leadership as a model that can be implemented by clinical instructors during clinical education. Effective leadership occurs when the leadership style is matched with the observed followers' characteristics. Effective leaders anticipate and assess change and adapt quickly and grow with the change, all while leading followers to do the same. As athletic training students' levels of readiness change, clinical instructors also need to transform their leadership styles and strategies to match the students' ever-changing observed needs in different situations. DATA SOURCES: CINAHL (1982-2002), MEDLINE (1990-2001), SPORT Discus (1949-2002), ERIC (1966-2002), and Internet Web sites were searched. Search terms included leadership, situational leadership, clinical instructors and leadership, teachers as leaders, and clinical education. DATA SYNTHESIS: Situational Leadership is presented as a leadership model to be used by clinical instructors while teaching and supervising athletic training students in the clinical setting. This model can be implemented to improve the clinical-education process. Situational leaders, eg, clinical instructors, must have the flexibility and range of skills to vary their leadership styles to match the challenges that occur while teaching athletic training students. CONCLUSIONS/RECOMMENDATIONS: This leadership style causes the leader to carry a substantial responsibility to lead while giving power away. Communication is one of the most important leadership skills to develop to become an effective leader. It is imperative for the future of the profession that certified athletic trainers continue to develop effective leadership skills to address the changing times in education and expectations of the athletic training profession.

  3. Alternative splicing of the maize Ac transposase transcript in transgenic sugar beet (Beta vulgaris L.). (United States)

    Lisson, Ralph; Hellert, Jan; Ringleb, Malte; Machens, Fabian; Kraus, Josef; Hehl, Reinhard


    The maize Activator/Dissociation (Ac/Ds) transposable element system was introduced into sugar beet. The autonomous Ac and non-autonomous Ds element excise from the T-DNA vector and integrate at novel positions in the sugar beet genome. Ac and Ds excisions generate footprints in the donor T-DNA that support the hairpin model for transposon excision. Two complete integration events into genomic sugar beet DNA were obtained by IPCR. Integration of Ac leads to an eight bp duplication, while integration of Ds in a homologue of a sugar beet flowering locus gene did not induce a duplication. The molecular structure of the target site indicates Ds integration into a double strand break. Analyses of transposase transcription using RT-PCR revealed low amounts of alternatively spliced mRNAs. The fourth intron of the transposase was found to be partially misspliced. Four different splice products were identified. In addition, the second and third exon were found to harbour two and three novel introns, respectively. These utilize each the same splice donor but several alternative splice acceptor sites. Using the SplicePredictor online tool, one of the two introns within exon two is predicted to be efficiently spliced in maize. Most interestingly, splicing of this intron together with the four major introns of Ac would generate a transposase that lacks the DNA binding domain and two of its three nuclear localization signals, but still harbours the dimerization domain.

  4. Misregulation of Alternative Splicing in a Mouse Model of Rett Syndrome.

    Directory of Open Access Journals (Sweden)

    Ronghui Li


    Full Text Available Mutations in the human MECP2 gene cause Rett syndrome (RTT, a severe neurodevelopmental disorder that predominantly affects girls. Despite decades of work, the molecular function of MeCP2 is not fully understood. Here we report a systematic identification of MeCP2-interacting proteins in the mouse brain. In addition to transcription regulators, we found that MeCP2 physically interacts with several modulators of RNA splicing, including LEDGF and DHX9. These interactions are disrupted by RTT causing mutations, suggesting that they may play a role in RTT pathogenesis. Consistent with the idea, deep RNA sequencing revealed misregulation of hundreds of splicing events in the cortex of Mecp2 knockout mice. To reveal the functional consequence of altered RNA splicing due to the loss of MeCP2, we focused on the regulation of the splicing of the flip/flop exon of Gria2 and other AMPAR genes. We found a significant splicing shift in the flip/flop exon toward the flop inclusion, leading to a faster decay in the AMPAR gated current and altered synaptic transmission. In summary, our study identified direct physical interaction between MeCP2 and splicing factors, a novel MeCP2 target gene, and established functional connection between a specific RNA splicing change and synaptic phenotypes in RTT mice. These results not only help our understanding of the molecular function of MeCP2, but also reveal potential drug targets for future therapies.

  5. TBX3 regulates splicing in vivo: a novel molecular mechanism for Ulnar-mammary syndrome.

    Directory of Open Access Journals (Sweden)

    Pavan Kumar P


    Full Text Available TBX3 is a member of the T-box family of transcription factors with critical roles in development, oncogenesis, cell fate, and tissue homeostasis. TBX3 mutations in humans cause complex congenital malformations and Ulnar-mammary syndrome. Previous investigations into TBX3 function focused on its activity as a transcriptional repressor. We used an unbiased proteomic approach to identify TBX3 interacting proteins in vivo and discovered that TBX3 interacts with multiple mRNA splicing factors and RNA metabolic proteins. We discovered that TBX3 regulates alternative splicing in vivo and can promote or inhibit splicing depending on context and transcript. TBX3 associates with alternatively spliced mRNAs and binds RNA directly. TBX3 binds RNAs containing TBX binding motifs, and these motifs are required for regulation of splicing. Our study reveals that TBX3 mutations seen in humans with UMS disrupt its splicing regulatory function. The pleiotropic effects of TBX3 mutations in humans and mice likely result from disrupting at least two molecular functions of this protein: transcriptional regulation and pre-mRNA splicing.

  6. TBX3 regulates splicing in vivo: a novel molecular mechanism for Ulnar-mammary syndrome. (United States)

    Kumar P, Pavan; Franklin, Sarah; Emechebe, Uchenna; Hu, Hao; Moore, Barry; Lehman, Chris; Yandell, Mark; Moon, Anne M


    TBX3 is a member of the T-box family of transcription factors with critical roles in development, oncogenesis, cell fate, and tissue homeostasis. TBX3 mutations in humans cause complex congenital malformations and Ulnar-mammary syndrome. Previous investigations into TBX3 function focused on its activity as a transcriptional repressor. We used an unbiased proteomic approach to identify TBX3 interacting proteins in vivo and discovered that TBX3 interacts with multiple mRNA splicing factors and RNA metabolic proteins. We discovered that TBX3 regulates alternative splicing in vivo and can promote or inhibit splicing depending on context and transcript. TBX3 associates with alternatively spliced mRNAs and binds RNA directly. TBX3 binds RNAs containing TBX binding motifs, and these motifs are required for regulation of splicing. Our study reveals that TBX3 mutations seen in humans with UMS disrupt its splicing regulatory function. The pleiotropic effects of TBX3 mutations in humans and mice likely result from disrupting at least two molecular functions of this protein: transcriptional regulation and pre-mRNA splicing.

  7. The Musashi 1 Controls the Splicing of Photoreceptor-Specific Exons in the Vertebrate Retina (United States)

    Murphy, Daniel; Carstens, Russ


    Alternative pre-mRNA splicing expands the coding capacity of eukaryotic genomes, potentially enabling a limited number of genes to govern the development of complex anatomical structures. Alternative splicing is particularly prevalent in the vertebrate nervous system, where it is required for neuronal development and function. Here, we show that photoreceptor cells, a type of sensory neuron, express a characteristic splicing program that affects a broad set of transcripts and is initiated prior to the development of the light sensing outer segments. Surprisingly, photoreceptors lack prototypical neuronal splicing factors and their splicing profile is driven to a significant degree by the Musashi 1 (MSI1) protein. A striking feature of the photoreceptor splicing program are exons that display a "switch-like" pattern of high inclusion levels in photoreceptors and near complete exclusion outside of the retina. Several ubiquitously expressed genes that are involved in the biogenesis and function of primary cilia produce highly photoreceptor specific isoforms through use of such “switch-like” exons. Our results suggest a potential role for alternative splicing in the development of photoreceptors and the conversion of their primary cilia to the light sensing outer segments. PMID:27541351

  8. Alternative splicing in the differentiation of human embryonic stem cells into cardiac precursors.

    Directory of Open Access Journals (Sweden)

    Nathan Salomonis


    Full Text Available The role of alternative splicing in self-renewal, pluripotency and tissue lineage specification of human embryonic stem cells (hESCs is largely unknown. To better define these regulatory cues, we modified the H9 hESC line to allow selection of pluripotent hESCs by neomycin resistance and cardiac progenitors by puromycin resistance. Exon-level microarray expression data from undifferentiated hESCs and cardiac and neural precursors were used to identify splice isoforms with cardiac-restricted or common cardiac/neural differentiation expression patterns. Splice events for these groups corresponded to the pathways of cytoskeletal remodeling, RNA splicing, muscle specification, and cell cycle checkpoint control as well as genes with serine/threonine kinase and helicase activity. Using a new program named AltAnalyze (, we identified novel changes in protein domain and microRNA binding site architecture that were predicted to affect protein function and expression. These included an enrichment of splice isoforms that oppose cell-cycle arrest in hESCs and that promote calcium signaling and cardiac development in cardiac precursors. By combining genome-wide predictions of alternative splicing with new functional annotations, our data suggest potential mechanisms that may influence lineage commitment and hESC maintenance at the level of specific splice isoforms and microRNA regulation.

  9. Supplementary Material for: Herboxidiene triggers splicing repression and abiotic stress responses in plants

    KAUST Repository

    Alshareef, Sahar


    Abstract Background Constitutive and alternative splicing of pre-mRNAs from multiexonic genes controls the diversity of the proteome; these precisely regulated processes also fine-tune responses to cues related to growth, development, and stresses. Small-molecule inhibitors that perturb splicing provide invaluable tools for use as chemical probes to uncover the molecular underpinnings of splicing regulation and as potential anticancer compounds. Results Here, we show that herboxidiene (GEX1A) inhibits both constitutive and alternative splicing. Moreover, GEX1A activates genome-wide transcriptional patterns involved in abiotic stress responses in plants. GEX1A treatment -activated ABA-inducible promoters, and led to stomatal closure. Interestingly, GEX1A and pladienolide B (PB) elicited similar cellular changes, including alterations in the patterns of transcription and splicing, suggesting that these compounds might target the same spliceosome complex in plant cells. Conclusions Our study establishes GEX1A as a potent splicing inhibitor in plants that can be used to probe the assembly, dynamics, and molecular functions of the spliceosome and to study the interplay between splicing stress and abiotic stresses, as well as having potential biotechnological applications.

  10. Benefits of CO2 laser heating for high reliability fiber splicing (United States)

    Duke, Douglas M.; Nasir, Usman; Saravanos, Elli


    The use of a CO2 laser as a heat source became commercially available for optical fiber splicing and component fabrication only in recent years. In addition to long-term trouble-free and low-maintenance heat source operation, laser fusion splicing offers unique benefits for fabricating high-power optical components, as well as for splice reliability. When used as the heating method for fiber splicing, the energy of the CO2 laser beam is efficiently absorbed by the outer layer of the glass, and is then conducted inwards. This heating method is well controlled, and results in a smooth and contamination-free glass surface. Other heating methods, such as arc fusion or resistive heating, may leave tungsten, graphite, or metal oxide deposits on the spliced fiber surface. By contrast, with CO2 laser splicing, the lack of surface irregularities and contamination enables remarkable spliced-fiber strength results, with some strength results nearly within the range of coated fiber breaking strength.

  11. LEADER 7 : Cardiovascular risk profiles of US and European participants in the LEADER diabetes trial differ

    NARCIS (Netherlands)

    Rutten, Guy E H M; Tack, Cees J.; Pieber, Thomas R.; Comlekci, Abdurrahman; Ørsted, David Dynnes; Baeres, Florian M M; Marso, Steven P.; Buse, John B.


    Aims: To determine whether US and European participants in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial differ regarding risk factors for cardiovascular mortality and morbidity. Methods: Baseline data, stratified for prior cardiovascular

  12. Take me to my leader: the importance of ethical leadership among formal nurse leaders. (United States)

    Storch, Janet; Schick Makaroff, Kara; Pauly, Bernie; Newton, Lorelei


    Although ethical leadership by formal nurse leaders is critical to enhancing ethical health-care practice, research has shown that many nurses feel unsupported by their leaders. In this article, we consider the limited attention directed toward ethical leadership of formal nurse leaders and how our own research on ethical nurse leadership compares to other research in this field. In searching Nursing Ethics since its inception 20 years ago, we found only a dozen articles that directly addressed this topic. We then reviewed nurses' professional codes of ethics in Canada and found significant retractions of ethical guidelines for formal nurse leaders' ethical responsibilities over the past decade. We began to seek explanations of why this is so and offer some recommendations for the study and enhancement of ethics for formal nurse leadership.

  13. The role of vertical conflict in the relationship between leader self-enhancement and leader performance

    NARCIS (Netherlands)

    van der Kam, Niels A.; Janssen, Onne; van der Vegt, Geert; Stoker, Janka I.

    Although studies have shown that inflated self-perceptions of transformational leadership behavior negatively affect leader performance, insight into the underlying processes explaining this relationship is lacking. The current study addresses this gap by identifying vertical conflict between

  14. A method of predicting changes in human gene splicing induced by genetic variants in context of cis-acting elements

    Directory of Open Access Journals (Sweden)

    Hicks Chindo


    Full Text Available Abstract Background Polymorphic variants and mutations disrupting canonical splicing isoforms are among the leading causes of human hereditary disorders. While there is a substantial evidence of aberrant splicing causing Mendelian diseases, the implication of such events in multi-genic disorders is yet to be well understood. We have developed a new tool (SpliceScan II for predicting the effects of genetic variants on splicing and cis-regulatory elements. The novel Bayesian non-canonical 5'GC splice site (SS sensor used in our tool allows inference on non-canonical exons. Results Our tool performed favorably when compared with the existing methods in the context of genes linked to the Autism Spectrum Disorder (ASD. SpliceScan II was able to predict more aberrant splicing isoforms triggered by the mutations, as documented in DBASS5 and DBASS3 aberrant splicing databases, than other existing methods. Detrimental effects behind some of the polymorphic variations previously associated with Alzheimer's and breast cancer could be explained by changes in predicted splicing patterns. Conclusions We have developed SpliceScan II, an effective and sensitive tool for predicting the detrimental effects of genomic variants on splicing leading to Mendelian and complex hereditary disorders. The method could potentially be used to screen resequenced patient DNA to identify de novo mutations and polymorphic variants that could contribute to a genetic disorder.

  15. Virtual potentials for feedback traps. (United States)

    Jun, Yonggun; Bechhoefer, John


    The recently developed feedback trap can be used to create arbitrary virtual potentials, to explore the dynamics of small particles or large molecules in complex situations. Experimentally, feedback traps introduce several finite time scales: There is a delay between the measurement of a particle's position and the feedback response, the feedback response is applied for a finite update time, and a finite camera exposure integrates motion. We show how to incorporate such timing effects into the description of particle motion. For the test case of a virtual quadratic potential, we give the first accurate description of particle dynamics, calculating the power spectrum and variance of fluctuations as a function of feedback gain, testing against simulations. We show that for small feedback gains, the motion approximates that of a particle in an ordinary harmonic potential. Moreover, if the potential is varied in time, for example by varying its stiffness, the work that is calculated approximates that done in an ordinary changing potential. The quality of the approximation is set by the ratio of the update time of the feedback loop to the relaxation time of motion in the virtual potential.

  16. Alternative RNA Splicing in the Pathogenesis of Liver Disease

    Directory of Open Access Journals (Sweden)

    Nicholas J. G. Webster


    Full Text Available Non-alcoholic fatty liver disease (NAFLD is becoming increasingly prevalent due to the worldwide obesity epidemic and currently affects one-third of adults or about one billion people worldwide. NAFLD is predicted to affect over 50% of the world’s population by the end of the next decade. It is the most common form of liver disease and is associated with increased risk for progression to a more severe form non-alcoholic steatohepatitis, as well as insulin resistance, type 2 diabetes mellitus, cirrhosis, and eventually hepatocellular carcinoma. This review article will focus on the role of alternative splicing in normal liver physiology and dysregulation in liver disease.

  17. Splice variants of porcine PPHLN1 encoding periphilin-1

    DEFF Research Database (Denmark)

    Larsen, Knud Erik; Momeni, Jamal; Farajzadeh, Leila


    splice variants hereof. RT-PCR cloning using oligonucleotide primers derived from in silico sequences resulted in three PPHLN1 transcripts: a full-length mRNA and two transcript variant resulting in shorter proteins. The longest encoded periphilin-1, consisting of 373 amino acids, displays a high......The periphilin-1 protein is encoded by the PPHLN1 gene. Periphilin-1 is found in the cornified cell envelope during the terminal differentiation of keratinocyte at the outer layer of epidermis. In the current study we report on the cloning and characterization of the porcine PPHLN1 cDNA and two...... homology to the human periphilin-1 protein coded by the transcript variant 2 (91%). A shorter transcript variant (PPHLN1Sp1) contains a 1065-codon ORF, which is consistent with that of the authentic PPHLN1, but lacks a region of 57 bp spanning exon 7. Hence, the encoded polypeptide periphilin-1Sp1 consists...

  18. Novel Alternative Splice Variants of Mouse Cdk5rap2.

    Directory of Open Access Journals (Sweden)

    Nadine Kraemer

    Full Text Available Autosomal recessive primary microcephaly (MCPH is a rare neurodevelopmental disorder characterized by a pronounced reduction of brain volume and intellectual disability. A current model for the microcephaly phenotype invokes a stem cell proliferation and differentiation defect, which has moved the disease into the spotlight of stem cell biology and neurodevelopmental science. Homozygous mutations of the Cyclin-dependent kinase-5 regulatory subunit-associated protein 2 gene CDK5RAP2 are one genetic cause of MCPH. To further characterize the pathomechanism underlying MCPH, we generated a conditional Cdk5rap2 LoxP/hCMV Cre mutant mouse. Further analysis, initiated on account of a lack of a microcephaly phenotype in these mutant mice, revealed the presence of previously unknown splice variants of the Cdk5rap2 gene that are at least in part accountable for the lack of microcephaly in the mice.

  19. Splice-Switching Therapy for Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Katharina E. Meijboom


    Full Text Available Spinal muscular atrophy (SMA is a genetic disorder with severity ranging from premature death in infants to restricted motor function in adult life. Despite the genetic cause of this disease being known for over twenty years, only recently has a therapy been approved to treat the most severe form of this disease. Here we discuss the genetic basis of SMA and the subsequent studies that led to the utilization of splice switching oligonucleotides to enhance production of SMN protein, which is absent in patients, through a mechanism of exon inclusion into the mature mRNA. Whilst approval of oligonucleotide-based therapies for SMA should be celebrated, we also discuss some of the limitations of this approach and alternate genetic strategies that are currently underway in clinical trials.


    Directory of Open Access Journals (Sweden)

    Endina Putri Purwandari


    Full Text Available Image splicing is a form of digital image manipulation by combining two or more image into a new image. The application was developed through a passive approach using demosaicking and wavelet transformation method. This research purposed a method to implement the demosaicking and wavelet transform for digital image forgery detection with a passive approach. This research shows that (1 demosaicking can be used as a comparison image in forgery detection; (2 the application of demosaicking and wavelet transformation can improve the quality of the input image (3 demosaicking and wavelet algorithm are able to estimate whether the input image is real or fake image with a passive approach and estimate the manipulation area from the input image.