7 research outputs found
She was afraid to call it love (she called it swimming)
Treball de l'assignatura: El pensament de les Imatges: l’assaig
audiovisual, de segon trimestresdel mà ster en Estudis de Cinema i Audiovisual Contemporanis. Curs 2015-2016She was afraid to call it love, she called it swimming es un intento de recordar
esas imágenes que nunca hemos visto, de sentir de nuevo esas sensaciones
que no hemos conocido todavÃa. El film se construye a partir de extractos del
proyecto de Anne Charlotte Robertson "Five Year Diary" en la apropiación de
su búsqueda de alguien que ha desaparecido (Emily) en el lugar donde fue
enterrado su cuerpo: el jardÃn. La voz que acompaña a las imágenes se
compone de fragmentos de diferentes libros que se presentan reordenados
como un viaje poético alrededor de otros tiempos y espacios.She was afraid to call it love, she called it swimming is an attempt to remember
those images that we have never seen, to feel again those feelings that we
haven't known yet. With this purpose we use excerpts from Anne Charlotte
Robertson's "Five Year Diary", a project on film. We appropriate her memories,
her search of that one who has gone away (called Emily) in the place where her
body was buried: the garden. The voice in the video reads a collection of
excerpts taken from different books and reordenated to compose a poetry piece
about the appropriation of the memories (expressed both in images and literary
text) from those who where here in the past and that we will never personally
meet because we live in different times and spaces
Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells
Molecular mechanisms underlying terminal differentiation of B cells into plasma cells are major determinants of adaptive immunity but remain only partially understood. Here we present the transcriptional and epigenomic landscapes of cell subsets arising from activation of human naive B cells and differentiation into plasmablasts. Cell proliferation of activated B cells was linked to a slight decrease in DNA methylation levels, but followed by a committal step in which an S phase-synchronized differentiation switch was associated with an extensive DNA demethylation and local acquisition of 5-hydroxymethylcytosine at enhancers and genes related to plasma cell identity. Downregulation of both TGF-β1/SMAD3 signaling and p53 pathway supported this final step, allowing the emergence of a CD23-negative subpopulation in transition from B cells to plasma cells. Remarkably, hydroxymethylation of PRDM1, a gene essential for plasma cell fate, was coupled to progression in S phase, revealing an intricate connection among cell cycle, DNA (hydroxy)methylation, and cell fate determination
Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells
Molecular mechanisms underlying terminal differentiation of B cells into plasma cells are major determinants of adaptive immunity but remain only partially understood. Here we present the transcriptional and epigenomic landscapes of cell subsets arising from activation of human naive B cells and differentiation into plasmablasts. Cell proliferation of activated B cells was linked to a slight decrease in DNA methylation levels, but followed by a committal step in which an S phase-synchronized differentiation switch was associated with an extensive DNA demethylation and local acquisition of 5-hydroxymethylcytosine at enhancers and genes related to plasma cell identity. Downregulation of both TGF-β1/SMAD3 signaling and p53 pathway supported this final step, allowing the emergence of a CD23-negative subpopulation in transition from B cells to plasma cells. Remarkably, hydroxymethylation of PRDM1, a gene essential for plasma cell fate, was coupled to progression in S phase, revealing an intricate connection among cell cycle, DNA (hydroxy)methylation, and cell fate determination
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia
Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with single-cell DNA/RNA-sequencing analyses and functional experiments, of 19 cases of CLL developing RT. Studying 54 longitudinal samples covering up to 19 years of disease course, we uncovered minute subclones carrying genomic, immunogenetic and transcriptomic features of RT cells already at CLL diagnosis, which were dormant for up to 19 years before transformation. We also identified new driver alterations, discovered a new mutational signature (SBS-RT), recognized an oxidative phosphorylation (OXPHOS)(high)-B cell receptor (BCR)(low)-signaling transcriptional axis in RT and showed that OXPHOS inhibition reduces the proliferation of RT cells. These findings demonstrate the early seeding of subclones driving advanced stages of cancer evolution and uncover potential therapeutic targets for RT.Single-cell genomic and transcriptomic analyses of longitudinal samples of patients with Richter syndrome reveal the presence and dynamics of clones driving transformation from chronic lymphocytic leukemia years before clinical manifestatio
Chromatin activation as a unifying principle underlying pathogenic mechanisms in multiple myeloma
Multiple myeloma (MM) is a plasma cell neoplasm associated with a broad variety of genetic lesions. In spite of this genetic
heterogeneity, MMs share a characteristic malignant phenotype whose underlying molecular basis remains poorly characterized.
In the present study, we examined plasma cells from MM using a multi-epigenomics approach and demonstrated
that, when compared to normal B cells, malignant plasma cells showed an extensive activation of regulatory elements, in
part affecting coregulated adjacent genes. Among target genes up-regulated by this process, we found members of the
NOTCH, NF-kB, MTOR signaling, and TP53 signaling pathways. Other activated genes included sets involved in osteoblast
differentiation and response to oxidative stress, all of which have been shown to be associated with the MM phenotype and
clinical behavior. We functionally characterized MM-specific active distant enhancers controlling the expression of thioredoxin
(TXN), a major regulator of cellular redox status and, in addition, identified PRDM5 as a novel essential gene for MM.
Collectively, our data indicate that aberrant chromatin activation is a unifying feature underlying the malignant plasma cell
phenotype