5,846 research outputs found
Encuentros con Elena Poniatowska
No full textThe author analyzes testimonial literature from the perspective of female literature through his meeting with Elena Poniatowska. An analysis of reality vs. Fiction in Elena, Jesusa and Tinisima.El autor analiza, desde su encuentro con Elena Poniatowska, la vertiente de la literatura testimonial como literatura de mujeres. Un análisis interior de la relación entre realidad y ficción, entre Elena, Jesusa o Tinísima
DISSECTING THE CONTRIBUTION OF THE HISTONE DEMETHYLASE LSD1 IN RETINOIC ACID-INDUCED DIFFERENTIATION OF APL CELLS
No full textAcute promyelocytic leukemia (APL) is a cytogenetically distinct subtype of acute myeloid leukemia, characterized by the chromosomal translocation t(15;17) that involves the retinoic acid receptor (RAR) gene and leads to the production of the fusion protein PML-RARα. In the past it has been successfully treated with all- trans retinoic acid at high doses to differentiate the leukemic blast. The fusion protein indeed retains the capability to binds DNA with an even stronger affinity and recruits repressive co-factors, making the cells insensitive to physiological concentrations of retinoic acid.
In the last few years, also the lysine-specific demethylase (LSD1) protein has emerged as important target for the epigenetic therapy of cancer.
We found that both pharmacological inhibition and knock down of LSD1 are able to sensitize NB4 cells - a cells line derived from an APL patient - to lower (physiological) doses of retinoic acid (RA) causing growth arrest and differentiation without degradation of the fusion protein. In order to elucidate the role of LSD1 in this mechanism, we characterized the LSD1 genomic distribution in acute myeloid leukemia by ChIP-seq experiment and performed RNA-seq and ChIP-seq for H3K4me1/me2/me3 and H3K27ac in all the four treatments (DMSO as control, RA low, RA high, LSD1 inhibition and cotreatment of LSD1 inhibitor and RA low).
Results of RNA-seq analyses show significant changes in gene expression only after co-treatment (RAlow + LSD1i) and RA high, in line with experimental evidence of phenotype. Moreover, in addition to an high overlap between genes expressed in both co-treatment and RAhigh, we observe a significative number of cotreatment-specific expressed genes that suggest a putative synergistic and stronger effect of the cotreatment compare to the retinoic acid high alone. In parallel, the data on histone modifications obtained through ChIP-seq experiments show a significant increase of the di-metylation of H3K4 after treatment with inhibitor. This mainly occurs in regions marked with peaks of LSD1 and associated with genes involved in cell differentiation (genes over- expressed in co-treatment, but not in other single treatments). In the same regions we observe the presence of H3K27 acetylation after treatment with retinoic acid but not after LSD1 inhibition. Only after treatment with both drugs the regions acquire the two histone marks, and we can observe an effective phenotype of differentiation, correlating with the observed change in gene expression. An hypothesis might be that there are regulatory regions linked by LSD1, which undergo a kind of “pre-mark” in histone modifications after treatment with the inhibitor (gain of H3K4me2) or with retinoic acid (gain of H3K27ac), which is necessary but not sufficient to determine a change in expression, found only after co-treatment in the simultaneous presence of both epigenetic modifications. Overall the combination of the LSD1 inhibition and RA low bypasses the block of PML-RAR fusion protein activating a different pathway of genes compared to RA high with stronger effects on the differentiation of the cells.
Taken together our results contribute to understand the role of LSD1 in the RA- induced differentiation of leukemic cells, suggest new therapeutic strategies for the intervention in APL and potentially other leukemias, and highlight the importance of combination therapies as new potent weapon in the cancer treatments
Bio-bibliografía de y sobre Elena Poniatowska Amor
No full textThe objective of this article is to collect and present: I. the chronology of the life and work of Elena Poniatowska; II. the complete works (as principal and secondary author), and III. the bibliography on the author (books, chapters, and articles).El objetivo de este artículo es reunir y presentar: I. los datos cronológicos fundamentales de la vida y la obra de Elena Poniatowska; II. El compendio de sus obras (como autora principal y como secundaria); y III. la bibliografía sobre la escritora (libros, capítulos de libros y artículos)
El Tlacuache Núm. 698 (2015). 698 Año 13 (2015) noviembre. El Tlacuache
No full textLa mujer vista por cronistas en tiempos novohispanos por Laura Elena Hinojosa. - El Códice Mauricio de la Arena forma parte de Los códices de Tlaquiltenango por Laura Elena Hinojosa
Self-renewal of tumor cells : Epigenetic determinants of the cancer stem cell phenotype
No full textAmong the functional subpopulations that coexist within the tumor, 'cancer stem cells' are characterized by increased self-renewal and the ability to derive all of the other subpopulations of tumor cells ('bulk'). The functional heterogeneity among cancer stem cells and bulk cells must reflect distinct cellular epigenetic landscapes, but - due to the difficulty to isolate bona fide cancer stem cells with a high degree of purity - those different epigenetic landscapes, and the molecular mechanisms underlying them, remain largely unknown. Cues of intratumor phenotypic plasticity complicate the interpretation of the cancer stem cell phenotype: we contend that, however, the concept of cancer stem cell has crucial therapeutic implication, and remains a key target for the exploration of the cancer epigenome
Encounters with Elena Poniatowska
No full textEl autor analiza, desde su encuentro con Elena Poniatowska, la vertiente de la literatura testimonial como literatura de mujeres. Un análisis interior de la relación entre realidad y ficción, entre Elena, Jesusa o Tinísima.The author analyzes testimonial literature from the perspective of female literature through his meeting with Elena Poniatowska. An analysis of reality vs. Fiction in Elena, Jesusa and Tinisima
Was There a Quiet Revolution? Belarus After the 2006 Presidential Election
No full textThe 2006 presidential election in Belarus mobilized a large cross-section of society to protest against the Lukashenko regime. Although unprecedented, the mass mobilization was short-lived, failing to develop into another kind of coloured revolution in the region. The key to our understanding of the endurance of Lukashenko's regime seems to lie in its internal environment, and notably, in the seemingly contradictory feature of the Belarusian electorate. Not only do they fully identify with the president, thus effectively legitimizing his politics and policies; they also do so knowingly, through their strategic learning of how to survive and even thrive under Lukashenko's regime. This type of learning, however, may not necessarily lead to a critical reflection of the regime's malpractice, and thus is unlikely to challenge its foundations
From trans-disciplinary to "undisciplined" design learning: educating through/to disruption
No full textThe paper is fruit of a coordinated work, however the author of paragraphs 1 and 4 is Flaviano Celaschi, the author of paragraph 2 is Elena Formia and the author of paragraphs 3 and 5 is Eleonora Lup
Black Fashion Designers Symposium: Elena Romero in conversation with Dapper Dan and Jeriana San Juan
No full textElena Romero in conversation with Dapper Dan and Jeriana San Juan at The Museum at FIT's annual fashion symposium, Black Fashion Designers, held on Monday, February 6, 2017.The one-day symposium featured talks by designers, models, journalists, and scholars on African diasporic culture and fashion.Elena Romero is an adjunct assistant professor at FIT. She is author of Free Stylin’: How Hip Hop Changed the Fashion Industry.Dapper Dan pioneered high-end street wear during the early 1980s. His celebrity clients include LL Cool J, Missy Elliott, and Jay Z.Jeriana San Juan is a costume designer and stylist currently working on the Baz Luhrmann series The Get Down
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