La frontera, borders an transborders. Reflections of the borderlands in Chicana Literature (early 20th-21st c.)

421 p.

Leukemia-Associated Mutations in Nucleophosmin Alter Recognition by CRM1: Molecular Basis of Aberrant Transport

Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein, normally enriched in nucleoli, that performs several activities related to cell growth. NPM mutations are characteristic of a subtype of acute myeloid leukemia (AML), where mutant NPM seems to play an oncogenic role. AML-associated NPM mutants exhibit altered subcellular traffic, being aberrantly located in the cytoplasm of leukoblasts. Exacerbated export of AML variants of NPM is mediated by the nuclear export receptor CRM1, and due, in part, to a mutationally acquired novel nuclear export signal (NES). To gain insight on the molecular basis of NPM transport in physiological and pathological conditions, we have evaluated the export efficiency of NPM in cells, and present new data indicating that, in normal conditions, wild type NPM is weakly exported by CRM1. On the other hand, we have found that AML-associated NPM mutants efficiently form complexes with CRM1HA (a mutant CRM1 with higher affinity for NESs), and we have quantitatively analyzed CRM1HA interaction with the NES motifs of these mutants, using fluorescence anisotropy and isothermal titration calorimetry. We have observed that the affinity of CRM1HA for these NESs is similar, which may help to explain the transport properties of the mutants. We also describe NPM recognition by the import machinery. Our combined cellular and biophysical studies shed further light on the determinants of NPM traffic, and how it is dramatically altered by AML-related mutations.

Pharmacogenetics of MicroRNAs and MicroRNAs Biogenesis Machinery in Pediatric Acute Lymphoblastic Leukemia

Despite the clinical success of acute lymphoblastic leukemia (ALL) therapy, toxicity is frequent. Therefore, it would be useful to identify predictors of adverse effects. In the last years, several studies have investigated the relationship between genetic variation and treatment-related toxicity. However, most of these studies are focused in coding regions. Nowadays, it is known that regions that do not codify proteins, such as microRNAs (miRNAs), may have an important regulatory function. MiRNAs can regulate the expression of genes affecting drug response. In fact, the expression of some of those miRNAs has been associated with drug response. Genetic variations affecting miRNAs can modify their function, which may lead to drug sensitivity. The aim of this study was to detect new toxicity markers in pediatric B-ALL, studying miRNA-related polymorphisms, which can affect miRNA levels and function. We analyzed 118 SNPs in pre-miRNAs and miRNA processing genes in association with toxicity in 152 pediatric B-ALL patients all treated with the same protocol (LAL/SHOP). Among the results found, we detected for the first time an association between rs639174 in DROSHA and vomits that remained statistically significant after FDR correction. DROSHA had been associated with alterations in miRNAs expression, which could affect genes involved in drug transport. This suggests that miRNA-related SNPs could be a useful tool for toxicity prediction in pediatric B-ALL.

Los "medici" en la epigrafía de la Hispania romana

[ES] La epigrafía latina nos permite conocer la existencia de veintiséis médicos en Hispania, los cuales llevaron a cabo su trabajo en diferentes ámbitos y especialidades. Gracias a la información de los textos de las inscripciones podemos estudiar cuestiones como el estatus socio-jurídico propio de los individuos dedicados a esta actividad, las posibles mejoras en el nivel económico de que pudieron ser objeto o los desplazamientos inherentes al ejercicio de la profesión. La mayor concentración de epígrafes en las antiguas Emerita Augusta y Gades nos hace pensar en estas ciudades como importantes centros médicos durante la época altoimperial en Hispania.

Lipid Nanoparticles as Carriers for RNAi against Viral Infections: Current Status and Future Perspectives

The efforts made to develop RNAi-based therapies have led to productive research in the field of infections in humans, such as hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), herpetic keratitis, human papillomavirus, or influenza virus. Naked RNAi molecules are rapidly digested by nucleases in the serum, and due to their negative surface charge, entry into the cell cytoplasm is also hampered, which makes necessary the use of delivery systems to exploit the full potential of RNAi therapeutics. Lipid nanoparticles (LNP) represent one of the most widely used delivery systems for in vivo application of RNAi due to their relative safety and simplicity of production, joint with the enhanced payload and protection of encapsulated RNAs. Moreover, LNP may be functionalized to reach target cells, and they may be used to combine RNAi molecules with conventional drug substances to reduce resistance or improve efficiency. This review features the current application of LNP in RNAi mediated therapy against viral infections and aims to explore possible future lines of action in this field.

Paper Art. Fibras papeleras en la Creación Artística. Producción y Edición

Nivel educativo: Grado. Duración (en horas): De 21 a 30 horas

Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles

Self-amplifying RNA or RNA replicon is a form of nucleic acid-based vaccine derived from either positive-strand or negative-strand RNA viruses. The gene sequences encoding structural proteins in these RNA viruses are replaced by mRNA encoding antigens of interest as well as by RNA polymerase for replication and transcription. This kind of vaccine has been successfully assayed with many different antigens as vaccines candidates, and has been shown to be potent in several animal species, including mice, nonhuman primates, and humans. A key challenge to realizing the broad potential of self-amplifying vaccines is the need for safe and effective delivery methods. Ideally, an RNA nanocarrier should provide protection from blood nucleases and extended blood circulation, which ultimately would increase the possibility of reaching the target tissue. The delivery system must then be internalized by the target cell and, upon receptor-mediated endocytosis, must be able to escape from the endosomal compartment into the cell cytoplasm, where the RNA machinery is located, while avoiding degradation by lysosomal enzymes. Further, delivery systems for systemic administration ought to be well tolerated upon administration. They should be safe, enabling the multiadministration treatment modalities required for improved clinical outcomes and, from a developmental point of view, production of large batches with reproducible specifications is also desirable. In this review, the concept of self-amplifying RNA vaccines and the most promising lipid-based delivery systems are discussed.

La jurisdicción voluntaria notarial. Su especial relevancia en el ámbito sucesorio

426 p.

Estrategias de desestabilización del estado oligomérico de la nucleofosmina

La nucleofosmina (NPM1) es una proteína nucleolar que juega un papel crítico en la biogénesis y exportación de ribosomas al citoplasma, la duplicación del centrosoma y los procesos de supresión tumoral. Se ha propuesto que para el desarrollo de sus múltiples funciones, la NPM, que es una proteína multidominio, presenta un equilibrio entre dos estados extremos, uno en el que su dominio N-terminal se encuentra plegado, lo que favorece su oligomerización, y otro en estado monomérico, que se encuentra globalmente desplegado. Nosotros queremos determinar los factores que desplazan el equilibrio hacia cada una de estas especies y el efecto de dicho polimorfismo en las funciones de la proteína.

RinA controls phage-mediated packaging and transfer of virulence genes in gram-positive bacteria

Phage-mediated transfer of microbial genetic elements plays a crucial role in bacterial life style and evolution. In this study, we identify the RinA family of phage-encoded proteins as activators required for transcription of the late operon in a large group of temperate staphylococcal phages. RinA binds to a tightly regulated promoter region, situated upstream of the terS gene, that controls expression of the morphogenetic and lysis modules of the phage, activating their transcription. As expected, rinA deletion eliminated formation of functional phage particles and significantly decreased the transfer of phage and pathogenicity island encoded virulence factors. A genetic analysis of the late promoter region showed that a fragment of 272 bp contains both the promoter and the region necessary for activation by RinA. In addition, we demonstrated that RinA is the only phage-encoded protein required for the activation of this promoter region. This region was shown to be divergent among different phages. Consequently, phages with divergent promoter regions carried allelic variants of the RinA protein, which specifically recognize its own promoter sequence. Finally, most Gram-postive bacteria carry bacteriophages encoding RinA homologue proteins. Characterization of several of these proteins demonstrated that control by RinA of the phage-mediated packaging and transfer of virulence factor is a conserved mechanism regulating horizontal gene transfer.

La guarda y custodia compartida de los hijos en el régimen del Código Civil

De acuerdo a la normativa de TFEs el repositorio no puede dar acceso a este trabajo. Para consultarlo póngase en contacto con el tutor del trabajo. Puede acceder al resumen del mismo pinchando en el pdf adjunto.

L'Ane promeneur, ou Critès promené par son ane : Chef-d'oeuvre pour servir d'Apologie au Goût, aux Moeurs, à l'Esprit, et aux Découvertes du siècle

Première edition revue, corrigée, et précédée d'une Préface à la Mosaïque, dans le plus nouveau goût.

Teatro critico universal, o Discursos varios en todo genero de materias, para desengaño de errores comunes

Nueva impresion, en la qual van puestas las adiciones del Suplemento en sus lugares.

Informe del proyecto Caldas- Subproyecto Aguadas.

146 hojas : ilustraciones, planos de productos.

Aspectos socio-económicos del municipio de Charalá: Técnicas del hilado y tejido en algodón.

91 hojas.