El mito de Lucía Miranda se reescribe en la versión de Eduarda Mansilla mediante la incorporación de la alambicada trama en el espacio europeo, ausente en el relato de Ruy Díaz de Guzmán. El análisis ...del espacio europeo arroja como resultado la primordial función narratológica que cumple Europa como escenario de múltiples mise en abyme, desde cuya perspectiva se resemantizará la trama en el espacio americano. Así, el mito de la cautiva blanca tomará en esta versión considerable distancia de la clásica dicotomía "civilización y barbarie", para promover de manera favorable los vínculos con la alteridad y para revalorar la imagen del indígena.
In her version of the story, Eduarda Mansilla rewrites the myth of Lucía Miranda by situating the convoluted plot in Europe, a world that is completely absent from the story narrated by Ruy Díaz de Guzmán. An analysis of this new space suggests that Europe plays a role of paramount narrative importance as the setting for multiple mise en abyme. When told from this new perspective, the action originally set in America acquires a new meaning. In Mansilla's version, the myth of the white captive steers well away from the classic dichotomy of "civilization and barbarism", promoting the bonds with otherness, and revaluating the image of the indigenous person.
Herpesviruses infect the majority of the human population and can cause significant morbidity and mortality. Herpes simplex virus (HSV) type 1 causes cold sores and herpes simplex keratitis, whereas ...HSV-2 is responsible for genital herpes. Human cytomegalovirus (HCMV) is the most common viral cause of congenital defects and is responsible for serious disease in immuno-compromised individuals. Epstein-Barr virus (EBV) is associated with infectious mononucleosis and a broad range of malignancies, including Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, and post-transplant lymphomas. Herpesviruses persist in their host for life by establishing a latent infection that is interrupted by periodic reactivation events during which replication occurs. Current antiviral drug treatments target the clinical manifestations of this productive stage, but they are ineffective at eliminating these viruses from the infected host. Here, we set out to combat both productive and latent herpesvirus infections by exploiting the CRISPR/Cas9 system to target viral genetic elements important for virus fitness. We show effective abrogation of HCMV and HSV-1 replication by targeting gRNAs to essential viral genes. Simultaneous targeting of HSV-1 with multiple gRNAs completely abolished the production of infectious particles from human cells. Using the same approach, EBV can be almost completely cleared from latently infected EBV-transformed human tumor cells. Our studies indicate that the CRISPR/Cas9 system can be effectively targeted to herpesvirus genomes as a potent prophylactic and therapeutic anti-viral strategy that may be used to impair viral replication and clear latent virus infection.
HIV presents one of the highest evolutionary rates ever detected and combination antiretroviral therapy is needed to overcome the plasticity of the virus population and control viral replication. ...Conventional treatments lack the ability to clear the latent reservoir, which remains the major obstacle towards a cure. Novel strategies, such as CRISPR/Cas9 gRNA-based genome-editing, can permanently disrupt the HIV genome. However, HIV genome-editing may accelerate viral escape, questioning the feasibility of the approach. Here, we demonstrate that CRISPR/Cas9 targeting of single HIV loci, only partially inhibits HIV replication and facilitates rapid viral escape at the target site. A combinatorial approach of two strong gRNAs targeting different regions of the HIV genome can completely abrogate viral replication and prevent viral escape. Our data shows that the accelerating effect of gene-editing on viral escape can be overcome and as such gene-editing may provide a future alternative for control of HIV-infection.
The intertextuality resulting from a continuous dialogue between numerous authors and the work of Saint John of the Cross can be traced —directly or
in a more subtle way— throughout the history of ...Spanish literature, from the Golden
Age until the present day. The present article analyzes concepts and images of
Saint John’s mysticism in the work of Blas de Otero that re-contextualizes them
in his postwar poetry, allow¬ing to grant a new semantic to the ideas and work of
Saint John of the Cross.
La recepción y la consecuente intertextualidad, fruto del diálogo ininterrumpido de los escritores con la obra de san Juan de la Cruz, puede rastrearse —en algunos casos en un primer nivel de lectura o de una manera más recóndita—, a lo largo de la historia de la literatura española desde el Siglo de Oro hasta la actualidad. En el presente trabajo destacaremos conceptos e imágenes de la místicasanjuanista de los que se apropia Blas de Otero, recontextualizándolos en su poesía de posguerra, dando lugar a un proceso de actualización y resemantización del pensamiento y obra sanjuanistas.
Trypanosomatids are single-cell eukaryotic parasites. Unlike higher eukaryotes, they control gene expression post-transcriptionally and not at the level of transcription initiation. This involves all ...known cellular RNA circuits, from mRNA processing to mRNA decay, to translation, in addition to a large panel of RNA-interacting proteins that modulate mRNA abundance. However, other forms of gene regulation, for example by lncRNAs, cannot be excluded. LncRNAs are poorly studied in trypanosomatids, with only a single lncRNA characterized to date. Furthermore, it is not clear whether the complete inventory of trypanosomatid lncRNAs is known, because of the inherent cDNA-recoding and DNA-amplification limitations of short-read RNA sequencing. Here, we overcome these limitations by using long-read direct RNA sequencing (DRS) on nanopore arrays. We analyze the native RNA pool of the two main lifecycle stages of the African trypanosome
with a special emphasis on the inventory of lncRNAs. We identify 207 previously unknown lncRNAs, 32 of which are stage-specifically expressed. We also present insights into the complexity of the
transcriptome, including alternative transcriptional start and stop sites and potential transcript isoforms, to provide a bias-free understanding of the intricate RNA landscape in
.
Type I IFNs play critical roles in orchestrating the antiviral defense by inducing direct antiviral activities and shaping the adaptive immune response. Viruses have evolved numerous strategies to ...specifically interfere with IFN production or its downstream mediators, thereby allowing successful infection of the host to occur. The prototypic human gammaherpesvirus EBV, which is associated with infectious mononucleosis and malignant tumors, harbors many immune-evasion proteins that manipulate the adaptive and innate immune systems. In addition to proteins, the virus encodes >40 mature microRNAs for which the functions remain largely unknown. In this article, we identify EBV-encoded miR-BART16 as a novel viral immune-evasion factor that interferes with the type I IFN signaling pathway. miR-BART16 directly targets CREB-binding protein, a key transcriptional coactivator in IFN signaling, thereby inducing CREB-binding protein downregulation in EBV-transformed B cells and gastric carcinoma cells. miR-BART16 abrogates the production of IFN-stimulated genes in response to IFN-α stimulation and it inhibits the antiproliferative effect of IFN-α on latently infected BL cells. By obstructing the type I IFN-induced antiviral response, miR-BART16 provides a means to facilitate the establishment of latent EBV infection and enhance viral replication.
The chromatin environment at origins of replication is thought to influence DNA replication initiation in eukaryotic genomes. However, it remains unclear how and which chromatin features control the ...firing of early-efficient (EE) or late-inefficient (LI) origins. Here, we use site-specific recombination and single-locus chromatin isolation to purify EE and LI replication origins in Saccharomyces cerevisiae. Using mass spectrometry, we define the protein composition of native chromatin regions surrounding the EE and LI replication start sites. In addition to known origin interactors, we find the microtubule-binding Ask1/DASH complex as an origin-regulating factor. Strikingly, tethering of Ask1 to individual origin sites advances replication timing (RT) of the targeted chromosomal domain. Targeted degradation of Ask1 globally changes RT of a subset of origins, which can be reproduced by inhibiting microtubule dynamics. Thus, our findings mechanistically connect RT and chromosomal organization via Ask1/DASH with the microtubule cytoskeleton.
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•Single-locus chromatin isolation shows distinct protein interactions at EE/LI origins•Ask1/DASH complex can regulate replication timing of ∼450 chromosomal locations•Ask1-activated regions are enriched for EE replication origins•Ask1-repressed regions are preferentially located at LI and inter-origin locations
Weiβ et al. establish a system of native single-locus chromatin isolation in yeast to identify proteins associated with distinct early-efficient (EE) or late-inefficient (LI) replication origins. The results identify the microtubule-binding Ask1/DASH complex as an origin-regulating factor that connects chromosomal organization in the nucleus with replication timing control.
El mito de LucÃa Miranda se reescribe en la versión de Eduarda Mansilla mediante la incorporación de la alambicada trama en el espacio europeo, ausente en el relato de Ruy DÃaz de Guzmán. El ...análisis del espacio europeo arroja como resultado la primordial función narratológica que cumple Europa como escenario de múltiples mise en abyme, desde cuya perspectiva se resemantizará la trama en el espacio americano. AsÃ, el mito de la cautiva blanca tomará en esta versión considerable distancia de la clásica dicotomÃa "civilización y barbarie", para promover de manera favorable los vÃnculos con la alteridad y para revalorar la imagen del indÃgena.
En el presente trabajo analizaremos las proyecciones borgeanas sobre la Divina Comedia, bajo la premisa de que la intertextualidad es un proceso deconstructivo en sí mismo, al que se suman los ...criterios del análisis de la subversión de los centros o anclajes de pensamiento dantescos y un proceso de autoproyección, mediante el cual Borges, con un acento marcadamente posmoderno, resemantiza y subvierte los pasajes más célebres de la Comedia, eclipsando la faceta medieval de la obra, en vistas a destacar sus propios presupuestos, vaciándola previamente de su contenido original. Las relaciones intertextuales entre Borges y Dante muestran cómo el argentino instrumentaliza y transforma la Comedia en pos de sus recurrentes ideas filosófico-literarias, sometiéndola a una especie de alquimia poética, arrojando como resultado un verdadero compendio de sus ideas filosóficas, dejando en evidencia que toda jerarquía y todo orden pueden ser subvertidos.
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