13,114 research outputs found

    Multiple tandem splicing silencer elements suppress aberrant splicing within the long exon 26 of the human Apolipoprotein B gene.

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    ABSTRACT: BACKGROUND: Apolipoprotein B (APOB) is an integral component of the chylomicron and the atherogenic lipoproteins LDL and Lp(a). Exon 26 of the APOB pre-mRNA is unusually long at 7,572 nt and is constitutively spliced. It is also subject to RNA editing in the intestine, which generates a shortened isoform, APOB48, assembled exclusively into chylomicrons. Due to its length, exon 26 contains multiple pseudo splice sites which are not spliced, but which conform to the degenerate splice site consensus. RESULTS: We demonstrate that these pseudo splice sites are repressed by multiple, tandem splicing silencers distributed along the length of exon 26. The distribution of these elements appears to be heterogeneous, with a greater frequency in the middle 4,800 nt of the exon. CONCLUSION: Repression of these splice sites is key to maintaining the integrity of exon 26 during RNA splicing and therefore the correct expression of both isoforms of APOB

    The problem of open cheating and invigilator compliance in the Lebanese Brevet and Baccalauréat examinations

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    This paper describes a study on examination room cheating during Lebanese Brevet and Baccalauréat examinations with a focus on 'open cheating' - malpractices which are aided and abetted by examination invigilators. Findings suggest that the problem is widespread and is largely attributable to the empathy invigilators feel with candidates. The collectivist ethos which has earlier been applied to collusion among cheating students appears to extend to invigilators during these high-stakes external examinations. It is suggested that behaviour modification strategies through organisational changes to the conduct of the examinations will be more effective than character development strategies in the short term. © 2010 Elsevier Ltd.Alutu Azuka N. G., 2006, Journal of Human Ecology, V20, P295; Bishop J. H., 1999, SWEDISH EC POLICY RE, V6, P349; Bishop JH, 1998, J ECON EDUC, V29, P171, DOI 10.2307-1183407; Bohte J, 2000, PUBLIC ADMIN REV, V60, P173, DOI 10.1111-0033-3352.00075; Cizek G. J., 1999, CHEATING TESTS DO IT; FIN KV, 2004, J EDUC RES, V97, P115; Heyneman S. P., 2004, INT J EDUC DEV, V24, P638; Jacob B. A., 2003, BROOKINGS WHARTON PA, P185; JURDAK M, 2009, SECONDARY SCH EXTERN; KOBIOWU SV, 2005, INT J AFRICAN AFRICA, V4, P39; KUEHN P, 1990, TESOL QUART, V24, P313, DOI 10.2307-3586911; McCabe DL, 2008, RES HIGH EDUC, V49, P451, DOI 10.1007-s11162-008-9092-9; McCabe DL, 2001, ETHICS BEHAV, V11, P219, DOI 10.1207-S15327019EB1103_2; *OFQUAL, 2009, STAT MALPR GCSE LEV; ROBERTSCADY S, 2008, INT J ED INTEGRITY, V4, P60; VLAARDINGERBROE.B, 2008, J VOCATIONAL ED TRAI, V60, P19, DOI 10.1080-13636820701828788; Vlaardingerbroek B, 2007, INT J EDUC DEV, V27, P564, DOI 10.1016-j.ijedudev.2006.09.002; Vlaardingerbroek Barend, 2009, SECONDARY SCH EXTERN; Wiliam D., 1996, CURRICULUM J, V7, P293; WOESSMANN L, 2001, ED MATTERS, P67; 2007, AL NAHAR 0717, P16; 2009, AL NAHAR 0505, P16; 2008, AL NAHAR 0712, P1610

    Live imaging of Drosophila gonad formation reveals roles for Six4 in regulating germline and somatic cell migration

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    Background: Movement of cells, either as amoeboid individuals or in organised groups, is a key feature of organ formation. Both modes of migration occur during Drosophila embryonic gonad development, which therefore provides a paradigm for understanding the contribution of these processes to organ morphogenesis. Gonads of Drosophila are formed from three distinct cell types: primordial germ cells (PGCs), somatic gonadal precursors (SGPs), and in males, male-specific somatic gonadal precursors (msSGPs). These originate in distinct locations and migrate to associate in two intermingled clusters which then compact to form the spherical primitive gonads. PGC movements are well studied, but much less is known of the migratory events and other interactions undergone by their somatic partners. These appear to move in organised groups like, for example, lateral line cells in zebra fish or Drosophila ovarian border cells.Results: We have used time-lapse fluorescence imaging to characterise gonadal cell behaviour in wild type and mutant embryos. We show that the homeodomain transcription factor Six4 is required for the migration of the PGCs and the msSGPs towards the SGPs. We have identified a likely cause of this in the case of PGCs as we have found that Six4 is required for expression of Hmgcr which codes for HMGCoA reductase and is necessary for attraction of PGCs by SGPs. Six4 affects msSGP migration by a different pathway as these move normally in Hmgcr mutant embryos. Additionally, embryos lacking fully functional Six4 show a novel phenotype in which the SGPs, which originate in distinct clusters, fail to coalesce to form unified gonads.Conclusion: Our work establishes the Drosophila gonad as a model system for the analysis of coordinated cell migrations and morphogenesis using live imaging and demonstrates that Six4 is a key regulator of somatic cell function during gonadogenesis. Our data suggest that the initial association of SGP clusters is under distinct control from the movements that drive gonad compaction.</p

    Inhibition effects of resveratrol on DEV <i>in vitro</i><sup>a</sup>.

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    a<p>The inhibition effects on DEV were evaluated by MTT assay.</p>b<p>Inhibition concentration 50% (IC<sub>50</sub>): concentration required to inhibit DEV at 72 h post-infection by 50%.(n = 3).</p>c<p>Cytotoxic concentration 50% (CC<sub>50</sub>) concentration required to reduce cell viability by 50%. (n = 3).</p>d<p>SI: Selectivity index is defined as the radio of CC<sub>50</sub> to IC<sub>50</sub>.</p

    Dev hücreli kemik tümöründe denosumab tedavisinin yeri: Literatürün gözden geçirilmesi

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    Denosumab kemik dev hücreli tümörünü yönetmek için etkili ve kullan l bir ilaçt r. noperable veya metastatik dev hücreli tümörlü hastalar için birinci basamak tedavide alt n standart olarak dü ünülmektedir. Dev hücreli kemik tümöründe denosumab netkinli i prospektifrandomize çal malarda kan tlanm t r. Nörovasküler yap lara yak n büyük dev hücreli tümörde daha fazla morbiditeye yol açaçak rezeksiyona yönelmek yerine denosumab ile neoadjuvan tedavi dev hücreli tümörde intralezyonel cerrahiyi kolayla t rabilir. Farkl sebeplerden dolay tedaviyi b rakt ktan sonra yap lan biyopside psödosarkomatöz de i iklikler görülebilece i unutulmamal d r. Dev hücreli tümörde denosumab tedavisi sonras kal nla m korteks ve subkondral kemik içerisinde tümör hücrelerinin gizlenmesi sonucu lokal tümör rekürrensi görülebilir. Denosumab çenede osteonekroz olu umu ile ili kilendirilmi tir. Bu makalede denosumab tedavisi alan hastalar n sistematik de erlendirilmesi,risk faktörleri, tan -tedavi yararl , tedavi seçeneklerini öngören k lavuzlar sunulmu tur.Denosumab is an effective and usefull drug for managing the giant cell bonetumor. It is considered the gold standard for treatment of the inoperable or metastatic giant cell tumors. Theefficacy of denosumab in giant cell bone tumors has been demonstrated in prospective randomized trials. Neoadjuvant therapy with denosumab may facilitate intralesional surgery in giant cell tumor instead of resection leading to more morbidity in a large giant cell tumor close to the neurovascular structure. It should not be forgotten that pseudosarcomatous changes in biopsies may ocur after denosumab treatment due to different reasons. Giant cell tumor may result in dense cortex after denosumab treatment and local tumor recurrence after concealment of tumor cells within the subchondral bone. Denosumab is associated with jaw osteonecrosis formation. In this article, guidelines for systematic evaluation, risk factors, diagnostic-therapeutic usefullness and treatment options for patients treated with denosumab are presented

    Analyzing sustainability knowledge in the Arab world

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    Building sustainability knowledge on the web is a vital path towards surpassing the barriers that could hinder sustainable development in any country in general. This paper presents the results of examining digital sustainability knowledge in the Arab world. A thorough examination and statistical analysis were performed on sustainable development websites that exist in all Arab countries during a specific period of time. The Global System for Sustainable Development (GSSD) is the knowledge management system used to store the sustainability knowledge in the region. The system is designed to be used by decision makers, scientists, educators and knowledge seekers. The main strength of the system is that it points users to needed knowledge on sustainable development that exists on the web. The search engine is the main driver and speakers of different languages can use it. Results indicate that most of the Arab countries have the same sustainable knowledge profile by showing existing problems and not solutions. Most of the information deals with issues related to wars and conflicts, migration and dislocation, and unmet basic needs, which reflect the political and social situation in many Arab countries. The paper concludes with some recommendations on how to improve sustainability knowledge on the web in the region. © 2010 John Wiley and Sons, Ltd. and ERP Environment.Bagheri A, 2007, SUSTAIN DEV, V15, P83, DOI 10.1002-sd.310; Basiago A. D., 1995, Sustainable Development (Bradford), V3, P109, DOI 10.1002-sd.3460030302; Choucri N, 2007, ALLIANCE GLOB SUSTAI, V11, P1, DOI 10.1007-978-1-4020-6071-7; Economic and Social Commission for Western Asia (ESCWA), 2005, Digital Arabic Content: Opportunities, Priorities and Strategies; Economic and Social Commission for Western Asia (ESCWA), 2005, REG PROF INF SOC W A; Economic and Social Commission for Western Asia (ESCWA), 2005, Statistical Information System ESIS; European Information Technology Observatory (EITO), 2002, About Digital Europe Project; Goldsmith E., 1972, ECOLOGIST, V2, P1; Hull Z, 2008, SUSTAIN DEV, V16, P73, DOI 10.1002-sd.337; Internet World Statistics (IWS), 2007, WORLD INT US POP STA; Johnson S, 2008, Politecnico Di Milano.; Khordagui H, 2004, SUSTAINABLE DEV ARAB; Kirsop B., 2007, ACCESS SCI KNOWLEDGE, P52; Mezher T, 1997, Sustainable Development, V5, P55, DOI 10.1002-(SICI)1099-1719(199708)5:255::AID-SD683.0.CO;2-L; Mezher T, 2002, SUSTAIN DEV, V10, P69, DOI 10.1002-sd.183; Minitab, 2008, More about Minitab Inc; Noamani D, 2008, Building Sustainability Knowledge in the Arab World Using the Global System For Sustainable Development; SMAP, 2008, Private Sector and Sustainable Development; UNDP (United Nations Development Programme), 2007, FIGHT CLIM CHANG HUM; United Nations, 2003, AR HUM DEV REP; United Nations (UN), 2007, The Millennium Development Goals in the Arab Region 2007: a Youth Lens; Upham P, 2000, SUSTAIN DEV, V8, P180, DOI 10.1002-1099-1719(200011)8:4180::AID-SD1433.3.CO;2-I; Warschauer M, 2003, TECHNOLOGY AND SOCIAL INCLUSION - RETHINKING THE DIGITAL DIVIDE, P1; WCED, 1987, OUR COMM FUT REP WOR; World Wildlife Foundation (WWF), 2002, Sustainability at the Speed of Light-Opportunities and Challenges for Tomorrow's Society0

    Estudi del factor de transcripció Cabut en el desenvolupament i la regeneració de Drosophila melanogaster

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    [cat] El procés de regeneració permet als organismes refer parts o teixits del seu cos que han sofert algun dany. Els discs imaginals de Drosophila melanogaster, primordis larvaris de les estructures adultes, tenen capacitat de promoure processos de cicatrització i proliferació, regenerant el teixit i donant lloc a estructures adultes completament normals. Hem estudiat el perfil d’expressió de discs d’ala a 0, 24 i 72h de regeneració. Els resultats obtinguts mostren un enriquiment significatiu de l’expressió de Factors de Transcripció lligats a importants vies de senyalització com Wingless (Wg), Notch (N) i Jun N-terminal Kinasa (JNK). Mitjançant la cerca computacional de motius d’unió d’AP-1 (factor de transcripció de la via de la JNK) en els promotors dels gens amb canvis d’expressió, hem descrit els gens diana d’aquesta la via procés durant la regeneració. Entre aquests gens es troba cabut (cbt), l’expressió del qual augmenta durant les primeres 24h i disminueix a les 72h, recuperant els seus nivells basals. Hem confirmat aquests resultats per qRT-PCR i amb tècniques d’hibridació in situ, demostrant a més, que l’increment de l’expressió de cbt està associat a cèl•lules del blastema. També hem comprovat que l’expressió de cbt augmenta per sobreactivació de la via de la JNK en el disc d’ala, tal i com s’havia vist prèviament en embrió. Mitjançant la tècnica EMSA hem validat la unió in vitro de les proteïnes Jun i DFos (que formen el dímer AP-1) a la seqüència predita en el promotor del gen cbt confirmant la regulació directe de la via de la JNK. L’anàlisi de discs mutants per cbt indica que l’expressió d’aquest gen és necessària per al tancament de la ferida i proliferació durant la regeneració. Cabut (Cbt) és un factor de transcripció Zn finger de la família dels Krüpple like Factors i els seus ortòleg en vertebrats són els gens TGFβ Inducible Early Genes (TIEG). Aquest gen s’ha descrit com a modulador de les vies Dpp i JAK/STAT en el disc d’ala. Una aproximació per descriure les funcions d’un factor de transcripció com Cbt és determinar els seus gens diana. Amb aquest objectiu hem realitzat un ChIP-Seq amb un anticòs contra la proteïna Cbt. Els resultats obtinguts mostren que Cbt es troba localitzat principalment als promotors dels gens. Aquest estudi ha reportat 2060 gens diana de Cbt en el disc d’ala. Les categories funcionals GO associades a aquest grup de gens són: Regulació de la transcripció, cicle cel•lular, desenvolupament dels discs imaginals i desenvolupament neuronal. També hem trobat un enriquiment en gens lligats a vies de senyalització com la JNK, Wg i N. L’anàlisi de les seqüències de les dianes de Cbt i altres estudis publicats apunten els factors Sin3A i GAF com a possibles cofactors de Cbt. Finalment hem analitzat el paper de Cbt en la regulació de la via de N, els resultats obtinguts mostren que Cbt regula positivament la via de N promovent el creixement i la formació del marge Dorso/Ventral del disc d’ala. Per tal d’establir quins factors de transcripció s’uneixen al promotor de cbt i regulen la seva expressió, hem realitzat un cribratge a gran escala utilitzant la tècnica de Yeast-One-Hybrid, que permet descriure la unió de factors de transcripció a una seqüència concreta. Hem obtingut factors de transcripció lligats al desenvolupament neural, a la segmentació i a la resposta immune amb capacitat d’unir-se al promotor de cbt. Aquestes dades no només ens donen informació sobre la regulació de Cbt sinó que també suggereixen la seva implicació en aquests processos. En conjunt el nostre treball mostra que Cbt regula el creixement i l’homeòstasi del disc d’ala durant el desenvolupament. I que quan es produeix un dany en aquest teixit l’expressió de Cbt incrementa, de manera depenent de la via de la JNK, per garantir la restauració del teixit perdut.[eng] Regeneration is the ability to rebuild a body part that has been damaged or amputated. Drosophila imaginal discs are able to undergo wound healing and regenerative growth after ablation. Genome-wide expression profiling of regenerating wing discs at 0, 24 and 72 hours after fragmentation have revealed a significant enrichment of transcription factors and chromatin regulators. To identify JNK target genes among the differentially expressed genes we performed a computational search of AP-1 binding sites in the promoter regions of these gens. Among them we identified cabut (cbt), the Drosophila ortholog of TGFβ Inducible Early Genes (TIEG). During regeneration cbt expression is induced between 0 and 24 and down-regulated between 24 and 72 hours, suggesting a tight and controlled mechanism of regulation. qRT-PCR and in situ hybridization experiments confirmed cbt expression changes and highlighted that cbt upregulation is associated to cells located in the blastema region. Moreover the analysis of regenerated cbt mutant discs demonstrated that cbt upregulation is required for wound healing and growth during regeneration. Cbt is a Zn finger transcription factor related to JNK and Dpp pathways, but few is known about its target genes. In order to identify Cbt target genes in development, we performed a Cbt ChIP-Seq analysis of wing discs from larvae III. This study reveal that Cbt is located mostly in the promoter regions of its target genes. We identified 2060 Cbt target genes which were related to functional categories such imaginal disc development, transcription regulation, neuron development or cell cycle. Furthermore several Cbt target genes were associated to signaling pathways like JNK, Wg or Notch (N). The analysis of cbt targets and previous reports pointed the factors GAF and Sin3A as a possible cofactors of Cbt. Finally, genetic interactions between cbt and N mutants demonstrated that Cbt regulates positively N signaling contributing to growth and Dorso/Ventral wing margin regulation. Although we have demonstrated that JNK is upstream of cbt, there is no much data available about cbt regulation in normal development. To approach this question we performed a high throughput Yeast-One-Hybrid screening that allowed us to defined factors that bind to cbt proximal promoter. The identified factors were related to immune response, neuron development and segmentation. Our results contributed to decipher cbt regulation network and suggested possible new roles for Cbt. In summary Cbt regulates growth and homeoastasis of wing disc during development. However in front of injury cbt is upregulated in a JNK dependent manner to ensure complete regeneration

    Cytochrome oxidase subunit VI of Trypanosoma brucei is imported without a cleaved presequence and is developmentally regulated at both RNA and protein levels

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    Mitochondrial respiration in the African trypanosome undergoes dramatic developmental stage regulation. This requires co-ordinated control of components encoded by both the nuclear genome and the kinetoplast, the unusual mitochondrial genome of these parasites. As a model for understanding the co-ordination of these genomes, we have examined the regulation and mitochondrial import of a nuclear-encoded component of the cytochrome oxidase complex, cytochrome oxidase subunit VI (COXVI). By generating transgenic trypanosomes expressing intact or mutant forms of this protein, we demonstrate that COXVI is not imported using a conventional cleaved presequence and show that sequences at the N-terminus of the protein are necessary for correct mitochondrial sorting. Analyses of endogenous and transgenic COXVI mRNA and protein expression in parasites undergoing developmental stage differentiation demonstrates a temporal order of control involving regulation in the abundance of, first, mRNA and then protein. This represents the first dissection of the regulation and import of a nuclear-encoded protein into the cytochrome oxidase complex in these organisms, which were among the earliest eukaryotes to possess a mitochondrion

    Optimizing the Performance of Electrostrictive Ceramics

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    LCSetter, N Israel Armament Dev Author,Pob 2250,Haifa,Israel Amp74 Times Cited:1 Cited References Count:
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