Letteratura scientifica selezionata sul tema "Super kabuki"

Este trabalho objetiva estudar o gênero kabuki, partindo de um panorama histórico para então comentar algumas performances recentes, como a do ator Kirk Nishikawa Dixon no filme curto “The Lion” e o denominado chôkabuki (que significa, literalmente, “super kabuki”), apresentando Konjaku Hana Kurabe Senbonzakura (“A festa das mil cerejeiras de ontem e de hoje”), com Shidô Nakamura e a vocaloid Hatsune Miku, um dos maiores ícones pop da atualidade no Japão. Discorre-se sobre a adaptabilidade do gênero kabuki e as características que permaneceram em meio a tantas mudanças: o papel do ator e sua relação com o público, o toque velado de transgressão e a inovação constante, corroborando o kabuki como um teatro popular do seu início até a contemporaneidade.

According to Jaqueline Berndt, Thomas LaMarre, and other critics, manga is a highly participatory media form. Narratives with vibrant characters and creative inconsistences in the plotline encourage the reader to recontextualise the text, create new contents and unfold activities which go beyond reading (such as fan art and CosPlay). Recent popularity of manga about Japanese traditional arts – for example, Kabuki – further expanded the potential interaction with manga and other popular media to include (re)discovering traditional Japanese culture. Examples, such as Kabukumon by Tanaka Akio and David Miyahara (Morning 2008-2011), or Kunisaki Izumo no jijō by Hirakawa Aya (Weekly Shōnen Sunday 2010-2014) and a variety of other manga, anime and light novels exemplify this tendency. Consequently, influential franchises, such as Naruto and One Piece boast adaptations as Super Kabuki stage-plays. Furthermore, Jessica Bauwens-Sugimoto observes how thematic and stylistic overreaching in contemporary manga further distort the notions of the gendered genre that lays at the foundation of the manga industry. In this case, Kabuki theatre as a theme employs a variety of gender fluid characters and situations. For this purpose, Kabuki manga utilise cross-genre narrative and stylistic tropes, from overtly parodying borrowed tropes, to homage, and covert inclusions. On the example of Kabuki-manga I will explore a larger trend in manga to employ elements of female genres in male narratives, thus expanding the target readership. My paper explores specific mechanism that facilitates reading manga cross-genre, I also inquire what novel critical potential thematic and stylistic exchange between audiences may entail.

Abstract EVI1 gene is located at 3q26.2 in the MECOM locus and encodes for a zinc-finger transcription factor. Chromosome translocation t(3;3) or inv(3) at 3q26 repositions the enhancer (E) of the tumor suppressor GATA2 to induce EVI1 over-expression, while concomitantly repressing GATA2. EVI1 over-expression promotes self-renewal and blocks differentiation of leukemia stem-progenitor cells (LSCs) and causes therapy refractoriness and inferior overall survival in AML. Previous reports highlighted that targeting BRD4 with BET inhibitor (BETi) is active against AML cells with inv(3)/t(3;3). BETi treatment also represses EVI1 and its targets c-Myc and Bcl-xL. We recently reported that tegavivint (TV) (BC-2059), a disruptor of the nuclear TBL1/R1-β-catenin-TCF7L2 complex represses c-Myc, cyclin D1 and Survivin and inhibits growth and survival of AML LSCs. In present studies, a CRISPR screen in UCSD-AML1 cells (with 3q26 lesion and EVI1 overexpression) with gRNAs targeting epigenetic regulators highlighted BRD4 and p300 as dependencies. Treatment with BETi, e.g., OTX015, dose-dependently induced apoptosis of AML cell lines and patient-derived (PD) AML cells (AML191 and AML194) with inv(3) or t(3;3). OTX015 treatment repressed c-Myc, c-Myb, CDK4, MECOM, and MCL1, while inducing HEXIM1 and cleaved PARP levels. TV treatment also dose-dependently induced apoptosis in AML cell lines and PD AML cells with 3q26.2 lesions, associated with depletion of nuclear β-catenin, EVI1, TCF7L2, c-Myc, c-Myb, RUNX1, CEBPα, c-KIT, BCL2, Bcl-xL and MCL1, but increase in p21, CD11b, BIM and cleaved PARP levels. Hi-ChIP with H3K27Ac antibody demonstrated that TV treatment abolished chromatin loops between MYC and its Es within the super-E. RNA-Seq analysis showed negative enrichment (log2-fold) of gene sets of MYC, E2F and WNT targets, DNA replication/repair and reduction of the 17-gene stemness score. Confocal microscopy showed that TV treatment disrupted co-localization of EVI1 and β-catenin with TBL1, also confirmed by the Proximity Ligation Assay. CyTOF analysis confirmed that TV treatment reduced EVI1, c-Myc, RUNX1, β-catenin, Bcl-xL, BCL2, MCL1 and Ki67 but increased cleaved PARP levels in the phenotypically characterized LSCs (with high expression of CLEC12A, CD123, CD244 and CD99) harboring inv(3) with EVI1 overexpression. Co-treatment with OTX015 and TV or the p300 inhibitor GNE-049 synergistically induced in vitro apoptosis in the AML cell lines and the PD AML cells with 3q26.2 lesions. Notably, in the flank-implanted PDX of AML191 or tail-vein infused PDX of AML242 models in NSG mice, treatment with OTX015 and TV, compared to vehicle control or each drug alone, significantly reduced AML growth and improved survival, without any host toxicity. These findings highlight the promising pre-clinical efficacy of novel BETi-based combinations against AML models harboring 3q26 lesions and EVI1 overexpression. Citation Format: Christine E. Birdwell, Warren C. Fiskus, Tapan M. Kadia, Christopher P. Mill, John A. Davis, Kaberi Das, Stephen Horrigan, Kapil N. Bhalla. Preclinical efficacy of targeting epigenetic mechanisms in AML with 3q26 lesions and EVI1 overexpression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4900.

Abstract In AML with MLL1 rearrangement or MLL1 fusion proteins (FP), the N-terminus of MLL1 becomes fused to over 80 partner proteins resulting in an aberrant leukemic transcriptional program including dysregulated expression of HOXA9, MEIS1, PBX3, FLT3, MEF2C and CDK6. On the other hand, in mutant NPM1 AML cells, wild type MLL1 is the main regulator of HOXA9, MEIS1 and FLT3, promoting self-renewal of myeloid progenitor cells. Menin inhibitors have been developed that disrupt the binding of Menin to MLL1 leading to reduced activity of HOXA9 and MEIS1 and repression of MLL1 or MLL1-FP target genes. Clinical trials have demonstrated that Menin inhibitors (MI) are well-tolerated and clinical remissions have been observed in patients with relapsed/refractory AML harboring MLLr. Unfortunately, most patients either fail to respond or eventually relapse. MI-resistance in AML with MLL1r or mtNPM1 is either due to recently described mutations in the MI-binding domain of Menin or is non-genetic/adaptive, due to dysregulated epigenome/transcriptome/proteome. In the present studies, through repeated shocks with LD90 dosing of MI, followed by drug washout and recovery, we have generated MLL1r (MV4-11-MITR) and mtNPM1 (OCI-AML3-MITR) AML cell lines that are tolerant/resistant (TR) to MI with LD50 values greater than 1 μM. Whole exome sequencing confirmed that these cells were lacking in new driver mutations. We determined that resistance in the MITR cells was not due to presence of hotspot mutations in Menin. ChIP-Seq analysis of H3K27Ac showed that the activities of super enhancers and core transcriptional regulatory circuitry was altered in both MITR cell types. Non-genetic/adaptive resistance to MI also concordantly reduced genome wide ATAC-Seq and RNA-Seq peaks in the OCI-AML3-MITR cells with significant depletion of MEIS1, IGF2BP2, BCL2, and PBX3, with concomitant induction of leukemia stem cell associated CLEC12A and CD244 expressions. A domain-specific CRISPR screen in MV4-11-MITR cells identified several druggable co-dependencies (e.g. EP300 and MOZ) and co-enrichments (SMARCA4, CREBBP and BRD4) with MI, suggesting them as potential mechanisms of non-genetic/adaptive MI resistance. Consistent with these findings, co-treatment with SMARCA2/SMARCA4 (chromatin remodeler ATPases) inhibitor FHD-286 and the BETi OTX015 or the MI SNDX-50469 exerted synergistic lethality in MV4-11-MITR and OCI-AML3-MITR cells as well as in PD MITR AML cells with MLL1r or mtNPM1. Co-treatment with CBP/p300 inhibitor GNE049 or GNE781 was also synergistic with MI in these cells. In vivo treatment with FHD-286 and OTX015 or SNDX-5613 significantly reduced the AML burden in mice bearing OCI-AML3-MITR xenografts. These findings underscore preclinical activity of epigenetically-targeted agent-based combinations and highlight their promise in overcoming MI resistance in AML with MLL1r or mtNPM1. Citation Format: Warren C. Fiskus, Christopher P. Mill, Jessica Piel, Murphy Hentemann, Christine E. Birdwell, Kaberi Das, John A. Davis, Hanxi Hou, Tapan M. Kadia, Naval Daver, Sanam Loghavi, Branko Cuglievan, Courtney D. DiNArdo, Kapil N. Bhalla. Novel combination therapies to overcome non-genetic/adaptive menin inhibitor resistance in AML with MLL1r or mtNPM1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1227.

Digital natives’ generation is inseparable from gadgets, less socializing, lack of creativity and being an individualist. The digital native’s generation wants things that are instant and lack respect for the process. The preoccupation of children with gadgets makes children socially alienated or known as anti-social. Preschool play an important role in the development of the digital native’s generation and in the future can help children use gadgets with parents. As it is known, the digital native’s generation is a kindergarten child. This study aims to determine the role of preschools in helping the use of gadgets in the digital native generation. This study used a descriptive quantitative approach with simple random sampling technique was obtained 25 kindergarten principals in Pekanbaru City. Data was collected in the form of a questionnaire via google form. Data analysis uses percentages and is presented in the tabular form. The results of the study indicate that the role of preschools in the use of gadgets in digital native generation children in Pekanbaru City is included in the low category. Only a few preschools have organized parenting education for parents. There are almost no rules governing children's use of gadgets at home, and few preschools educate children on how to use gadgets properly. It is expected for teachers and preschools to add special programs in the curriculum to provide information about positive gadget use and parenting programs that discuss digital native generation and collaborate with parents to establish rules such as frequency, duration and content of children using gadgets. Keywords: Digital Native, Preschool, Gadgets References: Alia, T., & Irwansyah, I. (2018). Pendampingan orang tua pada anak usia dini dalam penggunaan teknologi digital [parent mentoring of young children in the use of digital technology]. Polyglot: Jurnal Ilmiah, 14(1), 65–78. Allen, K. A., Ryan, T., Gray, D. L., McInerney, D. M., & Waters, L. (2014). Social Media Use and Social Connectedness in Adolescents: The Positives and the Potential Pitfalls. The Australian Educational and Developmental Psychologist, 31(1), 18–31. https://doi.org/10.1017/edp.2014.2 Berlin, A., Törnkvist, L., & Barimani, M. (2016). Content and Presentation of Content in Parental Education Groups in Sweden. The Journal of Perinatal Education, 25(2), 87–96. https://doi.org/10.1891/1058-1243.25.2.87 Chapman, G., & Pellicane, A. (2014). Growing up social: Raising relational kids in a screen-driven world. Moody Publishers. Cho, K.-S., & Lee, J.-M. (2017). Influence of Smartphone Addiction Proneness of Young Children on Problematic Behaviors and Emotional Intelligence. Comput. Hum. Behav., 66(C), 303–311. https://doi.org/10.1016/j.chb.2016.09.063 Coie, J. D., & Dodge, K. A. (1988). Multiple sources of data on social behavior and social status in the school: A cross-age comparison. Child Development, 815–829. Crouch, A. (2017). Tech-Wise Family. Everyday Steps for Putting Technology in Its Proper Place. Baker Books. De Lima, L., & Castronuevo, E. (2016). Perception of parents on children’s use of gadgets. The Bedan Journal of Psychology, II, 26–34. Gani, S. A. (2017). Parenting Digital Natives: Cognitive, Emotional, and Social Developmental Challenges. Guralnick, M. J. (1999). Family and child influences on the peer‐related social competence of young children with developmental delays. Mental Retardation and Developmental Disabilities Research Reviews, 5(1), 21–29. Hosokawa, R., & Katsura, T. (2018). Association between mobile technology use and child adjustment in early elementary school age. PloS One, 13(7), e0199959. Jonathan, L. P., & Andrew, L. F. (2016). Depression in children and adolescents. University of Kansas, Clinical Child Psychology Program. Kabali, H. K., Irigoyen, M. M., Nunez-Davis, R., Budacki, J. G., Mohanty, S. H., Leister, K. P., & Bonner, R. L. (2015). Exposure and Use of Mobile Media Devices by Young Children. PEDIATRICS, 136(6), 1044–1050. https://doi.org/10.1542/peds.2015-2151 Kirschner, P. A., & De Bruyckere, P. (2017). The myths of the digital native and the multitasker. Teaching and Teacher Education, 67, 135–142. https://doi.org/10.1016/j.tate.2017.06.001 Kurniawan, A. R., Chan, F., Sargandi, M., Yolanda, S., Karomah, R., Setianingtyas, W., & Irani, S. (2019). Kebijakan Sekolah Dalam Penggunaan Gadget di Sekolah Dasar [School Policy on the Use of Gadgets in Elementary Schools]. Jurnal Tunas Pendidikan, 2(1), 72–81. Martin, D. J. (2001). Constructing Early Childhood Science. Delmar Thomson Learning, Inc,. Morrongiello, B. A., McArthur, B. A., Goodman, S., & Bell, M. M. (2015). Don’t touch the gadget because it’s hot! Mothers’ and children’s behavior in the presence of a contrived hazard at home: Implications for supervising children. Journal of Pediatric Psychology, 40 1, 85–95. Mueller, S., Remaud, H., & Chabin, Y. (2011). How strong and generalisable is the Generation Y effect? A cross‐cultural study for wine. International Journal of Wine Business Research, 23(2), 125–144. https://doi.org/10.1108/17511061111142990 NAEYC. (2012). Technology and interactive media as tools in early childhood programs serving children from birth through age 8. National Institute for Educational Policy Research. (2014). Zenkoku Gakuryoku Gakusyu Jyokyo Cyosa [Japanese]. Nielsen Company. (2009). Television, Internet, and mobile usage in the U.S.: A2/M2 Three Screen Report. Nielsen Company. Nielsen, M. (2012). Imitation, pretend play, and childhood: Essential elements in the evolution of human culture? Journal of Comparative Psychology, 126(2), 170–181. https://doi.org/10.1037/a0025168 Novianti, R., Febrialismanto, F., Puspitasari, E., & Hukmi, H. (2020). Meningkatkan pengetahuan orang tua dalam mendidik anak di era digital di Kecamatan Koto Gasib Kabupaten Siak Provinsi Riau [Increasing parental knowledge in educating children in the digital era in Koto Gasib Sub-district, Siak Regency, Riau Province]. Riau Journal of Empowerment, 3(3), 183–190. https://doi.org/10.31258/raje.3.3.183-190 Novianti, R., & Garzia, M. (2020). Penggunaan Gadget pada Anak; Tantangan Baru Orang Tua Milenial[Use of Gadgets in Children; Millennial Parents' New Challenge]. Jurnal Obsesi: Jurnal Pendidikan Anak Usia Dini, 4(2), 1000–1010. Pediatrics, A. A. O. (2016). American Academy of Paediatrics announces new recommendations for children’s media use. Advocacy & Policy. Radesky, J. S., & Christakis, D. A. (2016). Increased Screen Time: Implications for Early Childhood Development and Behaviour. Paediatric Clinics of North America, 63(5), 827–839. https://doi.org/10.1016/j.pcl.2016.06.006 Ransdell, S., Kent, B., Gaillard-Kenney, S., & Long, J. (2011). Digital immigrants fare better than digital natives due to social reliance: Digital immigrants and social reliance. British Journal of Educational Technology, 42(6), 931–938. https://doi.org/10.1111/j.1467-8535.2010.01137.x Rideout, V., &. Robb, M. B., & Robb, M. B. (2020). The commonsense census: Media use by kids aged zero to eight. Common Sense Media. Scott, F. L. (2021). Family mediation of preschool children’s digital media practices at home. Learning, Media, and Technology, 1–16. https://doi.org/10.1080/17439884.2021.1960859 Setianingsih, S. (2018). Dampak penggunaan gadget pada anak usia prasekolah dapat meningkatan resiko gangguan pemusatan perhatian dan hiperaktivitas [The impact of using gadgets on preschool-aged children can increase the risk of attention deficit disorder and hyperactivity]. Gaster, 16(2), 191–205. Sharkins, K. A., Newton, A. B., Albaiz, N. E. A., & Ernest, J. M. (2016). Preschool Children’s Exposure to Media, Technology, and Screen Time: Perspectives of Caregivers from Three Early Childcare Settings. Early Childhood Education Journal, 44(5), 437–444. https://doi.org/10.1007/s10643-015-0732-3 Sheedy, A. J., Brent, J., Dally, K., Ray, K., & Lane, A. E. (2021). Handwriting Readiness among Digital Native Kindergarten Students. Physical & Occupational Therapy In Pediatrics, 41(6), 655–669. https://doi.org/10.1080/01942638.2021.1912247 Steiner-Adair, C., & Barker, T. H. (2013). The Big Disconnect (1st ed.). Harper Collins. Strasburger, V. C., Jordan, A. B., & Donnerstein, E. (2010). Health effects of media on children and adolescents. Pediatrics, 125(4), 756–767. Sugiyono. (2017a). Statistika untuk Penelitian[Statistics for Research]. Alfabeta. Sugiyono, P. (2017b). Metode Penelitian Pendidikan: Pendekatan Kuantitatif, Kualitatif, R&D [Educational Research Methods: Quantitative, Qualitative, R&D Approach]. Cetakan Ke-25. Bandung: CV Alfabeta. Suhana, M. (2018). Influence of Gadget Usage on Children’s Social-Emotional Development. 169(Icece 2017), 224–227. https://doi.org/10.2991/icece-17.2018.58 Sylva, K. (1994). School Influences on Children’s Development. Journal of Child Psychology and Psychiatry, 35(1), 135–170. https://doi.org/10.1111/j.1469-7610.1994.tb01135.x Takeuchi, H., Taki, Y., Hashizume, H., Asano, K., Asano, M., Sassa, Y., Yokota, S., Kotozaki, Y., Nouchi, R., & Kawashima, R. (2016). Impact of videogame play on the brain’s microstructural properties: Cross-sectional and longitudinal analyses. Molecular Psychiatry, 21(12), 1781–1789. Test, J. E., Cunningham, D. D., & Lee, A. C. (2010). Talking With Young Children: How Teachers Encourage Learning. Dimensions of Early Childhood, 38(3), 3–14. Tootell, H., Freeman, M., & Freeman, A. (2014). Generation Alpha at the Intersection of Technology, Play and Motivation. 2014 47th Hawaii International Conference on System Sciences, 82–90. https://doi.org/10.1109/HICSS.2014.19 Twenge, J. M. (2017). IGen: Why today’s super-connected kids are growing up less rebellious, more tolerant, less happy—And completely unprepared for adulthood—And what that means for the rest of us. Simon and Schuster. UNESCO. (2014). Information and Communication Technology (ICT) In Education in Asia. Information Papers, 6(22), 6. UNICEF. (2017). UNICEF for Every Child. The State of The World’s Children 2017. Children in a Digital World. Valkenburg, P. M., Peter, J., & Schouten, A. P. (2006). Friend Networking Sites and Their Relationship to Adolescents’ Well-Being and Social Self-Esteem. CyberPsychology & Behavior, 9(5), 584–590. ht

Abstract Kabuki Syndrome (KS) is a rare, multisystem disorder with a variable clinical phenotype. The majority of KS is caused by dominant loss-of-function mutations in KMT2D (lysine methyltransferase 2D). KMT2D mediates chromatin accessibility by adding methyl groups to lysine residue 4 of histone 3, which plays a critical role in cell differentiation and homeostasis. The molecular underpinnings of KS remain elusive partly due to a lack of histone modification data from human samples. Consequently, we profiled and characterized alterations in histone modification and gene transcription in peripheral blood mononuclear cells (PBMCs) from 33 patients with KMT2D mutations and 36 unaffected healthy controls. Our analysis identified unique enhancer signatures in H3K4me1 and H3K4me2 in KS compared to controls. Reduced enhancer signals were present for promoter-distal sites of immune-related genes for which co-binding of PBMC-specific transcription factors was predicted; thirty-one percent of super-enhancers of normal blood cells overlapped with disrupted enhancers in KS, supporting an association of reduced enhancer activity of immune-related genes with immune deficiency phenotypes. In contrast, increased enhancer signals were observed for promoter-proximal regions of metabolic genes enriched with EGR1 and E2F2 motifs, whose transcriptional levels were significantly increased in KS. Additionally, we identified approximately 100 de novo enhancers in genes, such as in MYO1F and AGAP2. Together, our results underscore the effect of KMT2D haploinsufficiency on dysregulation of enhancer states and gene transcription and provide a framework for the identification of therapeutic targets and biomarkers in preparation for clinical trial readiness.

Mantar meşesi (Quercus suber L.) kabuğundan faydalanılan değerli bir ağaçtır. Odun dışı orman ürünü olan mantarın, sanayi, gıda, otomotiv, izolasyon gibi çok farklı alanlarda kullanım imkânı bulunmaktadır. İzolasyon özelliğinin çok yüksek olması nedeniyle yüksek ses ve ısı izolasyon gerektiren alanlarda kullanılmaktadır. Akdeniz havzasının doğal türüdür ve yayılışının 1/3’ünü Portekiz’de yapmaktadır. Ülkemizde de farklı yaşlarda bireysel örnekleri bulunsa da ilk düzenli plantasyon 1975 yılında Torbalı Orman Fidanlığı içerisine 2 orijin ve 286 adet fidanla kurulmuştur. Bu ağaçlardan 1990 yılların 2. yarısından sonra tohum alınmaya ve fidan üretilmeye başlanmıştır. Bu fidanlar İzmir Orman Bölge Müdürlüğü’nde yapılan ağaçlandırma çalışmalarında kullanılmıştır. Kabuğundan faydalanılan bir ürün olduğundan ekolojisi gereği kaliteli kabuk oluşturabilmesi yetişme yeri koşullarına, özellikle büyük ölçüde iklime bağlıdır. Doğal yayılış alanlarındaki sert okyanus iklimi hem miktar hem de kalite bakımından kabuk oluşumunu etkilemektedir. Ülkemizde farklı yükselti, bakı ve toprak tiplerinde yapılan bu ilk ağaçlandırmalar 20 yaşını aşmış ve bazılarından kabuk üretimi yapılabilecek duruma gelmiştir. Bu ağaçlandırma çalışmalarının halihazırdaki durumlarının ortaya konulması, ülkemizin ihtiyacı olan bu değerli orman ürününün yetiştirilmesi ve ağaçlandırmalarda kullanılması için kıymetli bilgiler sağlayacaktır. Bu amaçla, ağaçlandırma çalışmaları incelenerek, toprak, yükselti ve bakının ağaçların boy ve çap gelişimi ile kabuk kalınlığı üzerindeki etkileri değerlendirilmiş, gelişim durumları ortaya konulmuştur. Mantar meşesi ağaçlarının alt rakımlarda boy büyümesinin, üst rakımlarda ise gövde çapı ve kabuk kalınlığının daha iyi geliştiği belirlenmiştir. Güneşli bakıların, gölgeli bakılara göre boy ve kabuk kalınlığı üzerinde anlamlı bir etkisinin olmadığı, çap artımında ise etkili bir faktör olduğu belirlenmiştir. Çalışma alanlarından alınan toprak örneklerinde tekstür killi balçık olarak belirlenmiştir. Topraklar tuzsuz (EC- 0,04), ortalama pH 7, CaCO3 % 0.3 ve organik madde % 1.8 olarak belirlenmiştir.