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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

The role of phosphorylation in the regulation of the chromokinesin Xkid

Ferreira, Vanessa Miriam dos Reis 22 November 2010 (has links)
Xkid is a Xenopus chromokinesin required for metaphase chromosome alignment and for meiosis I to meiosis II transition in oocytes. The aim of this work was to study the regulation of Xkid by phosphorylation using the Xenopus oocyte and egg extract systems. To achieve this, a reliable method to express proteins in egg extract by addition of in vitro transcribed mRNAs was established. Xkid was found to be efficiently phosphorylated in meiosis and mitosis at the cdk1 site. Although phosphoXkid localized efficiently to the mitotic chromosomes, phosphorylation at the cdk1 site had no role in the binding of Xkid to the chromosomes but prevented the protein to localize to the spindle microtubules like the endogenous protein. The dominant negative effect on spindle assembly of a phospho mimicking form of Xkid indicated that phosphorylation plays an important role in the regulation of Xkid function. Several partners for Xkid were identified. / Xkid es una cromoquinesina del sistema de Xenopus, necesaria para el alineamiento de los cromosomas en la placa metafásica y para la transición entre la meiosis I y meiosis II en los oócitos. El objectivo de este trabajo era estudiar la regulación de Xkid por fosforilación en los oócitos y en el extracto de huevos de Xenopus. Para poder cumplirlo se estableció un método para la expresión de proteínas añadiendo al extracto de huevos ARN mensajeros sintetizados in vitro. Los resultados obtenidos sugieren que Xkid es eficientemente fosforilada en el sitio cdk1 durante la meiosis y la mitosis. Aunque la forma de Xkid fosforilada se localiza eficientemente a nivel de los cromosomas mitóticos, esta fosforilación no parece tener ningún papel regulador sobre esta localización. En cambio, parece interferir con la localización de Xkid sobre los microtúbulos mitóticos. El efecto dominante negativo de la forma de Xkid que mimetiza la fosforilación durante la formación del huso mitótico, sugiere además que la fosforilación desempeña un papel importante en la regulación de la función de Xkid. Finalmente, varias proteínas que interaccionan con Xkid han sido identificadas.
12

The role of NIMA-like kinase Nek9 in mitosis

Schütz, Martin Maximilian 01 July 2011 (has links)
Mitosis is the essential process during which a cell divides into two viable daughter cells. To allow a faithful segregation of the chromosomes into each daughter, the cell forms the bipolar spindle. The NIMA-like kinase family member Nek9 has been previously proposed to play a role in bipolar spindle assembly and in the chromosomal pathway of microtubule assembly. We aimed at gaining a better understanding of Nek9 function by characterizing Xenopus Nek9, xNek9, using the Xenopus egg extract system. We have shown that xNek9 may not act through the kinase cascade xNek9 – xNek6 in meiosis as described for human Nek9 in somatic cells and therefore may have different substrates. Furthermore, we have demonstrated by depletion, increased addition of Flag-hNek9 and a dominant-negative approach that xNek9 is important for bipolar spindle formation. In addition, we have shown that xNek9 depletion causes decreased microtubule density in bipolar spindles and slower RanGTP induced aster formation. We identified xNedd1, the adaptor protein for the γTuRC, as a novel interactor and substrate of xNek9. xNek9 depletion reduces the recruitment of xNedd1 to sperm nuclei induced aster and decreases the number and length of nucleated microtubules. These data suggest that one role of xNek9 in spindle assembly is exerted through xNedd1 regulation. We propose a model for xNek9 – xNedd1 interaction and a putative mechanism for the regulation of xNek9 – xNedd1 explaining how they fulfil their role in bipolar spindle assembly. / La mitosis es el proceso esencial durante el cual una célula se divide en dos células hijas viables. Para permitir una segregación fiable de los cromosomas en cada hija, la célula forma el huso bipolar. Nek9, el miembro de la familia de quinasas NIMA-like ha sido propuesto para desempeñar un papel en el la asamblea del huso bipolar y en la vía cromosómica de ensamblaje de los microtúbulos. Nuestro objetivo era lograr una mejor comprensión de la función Nek9 caracterizando Nek9 de Xenopus, xNek9, utilizando el sistema de extracto de huevos de Xenopus. Hemos demostrado que xNek9 probablemente no actuará a través de la cascada de las quinasas xNek9 - xNek6 en la meiosis como se describe para Nek9 humano en células somáticas y por lo tanto pueden tener diferentes sustratos. Además, hemos demostrado por el agotamiento, la adición incrementada de Flag-hNek9 y un enfoque dominante-negativas que xNek9 es importante para la formación del huso bipolar. Además, hemos demostrado que el agotamiento xNek9 causa una disminución de la densidad de los microtúbulos en los husos bipolares y una formación más lenta de asteres inducidos por RanGTP. Se identificó xNedd1, la proteína adaptadora para el γTuRC, como un interactor y sustrato novedoso de xNek9. El agotamiento de xNek9 reduce la contratación de xNedd1 a los asteres inducidas por núcleos de espermatozoides y disminuye el número y longitud de microtúbulos nucleados. Estos datos sugieren que un papel de xNek9 en el conjunto del huso se husorce a través de la regulación de xNedd1. Proponemos un modelo para la interacción xNek9 – xNedd1 y un supuesto mecanismo para la regulación de xNek9 – xNedd1 explicando cómo cumplen su papel en la ensamblaje del huso bipolar.
13

Sequence-Dependent nucleosome positioning and chromatin remolleing of hormone-responsive genes

Zaurín Quer, Roser 16 July 2009 (has links)
Evidències recents han remarcat la importància del paper de l'estructura de la cromatina i el posicionament de nucleosomes en processos cel·lulars bàsics com és la regulació de la transcripció gènica. L'avenç de noves tecnologies en el camp ha permès l'estudi detallat de la disposició de nucleosomes en genomes sencers. Hi ha hagut també molts intents per definir les característiques de la seqüència de l'ADN que podrien arribar a guiar el posicionament dels nucleosomes; sent el conjunt d'aquestes característiques l'anomenat "codi nucleosòmic". En la present tesis doctoral, s'aporten evidències experimentals sobre l'existència d'un grup de nucleosomes molt ben posicionats en el genoma humà. Això ha estat possible mitjançant tècniques com els microarray i la seqüenciació massiva en paral·lel. Aquest treball mostra com aquests nucleosomes, que anomenem "nucleosomes clau", tenen tendència a ocupar regions del genoma amb funcions específiques, la qual cosa indica el seu paper especial. L'ADN els "nucleosomes clau" resulta tenir una alta simetria de curvatura. Aquesta característica inherent a la seqüència fa que sigui possible la predicció in silico de les posicions de nucleosomes d'aquest tipus. En la segona part de la present tesi doctoral, aporto noves evidències experimentals que fan avançar el camp de la organització de la cromatina i la seva dinàmica en el context de la regulació gènica. Les hormones esteroidees indueixen la transcripció dels seus gens diana a través de la unió dels receptors hormonals amb els seu corresponent motiu de reconeixement a l'ADN (HREs), així com el reclutament d'una gran varietat de co- eguladors. El promotor del Virus de Tumor Mamari de Ratolí (MMTV) ha estat un model molt usat per l'estudi dels efectes en l'activació gènica dels receptors hormonals. És conegut que el receptor de progesterona (PR) s'uniex a l'HRE1, accessible, i recluta maquinàries de remodelament de la cromatina que utilitzen l'ATP com a font energètica per expulsar els dimers d'histones H2A/H2B del nucleosoma B del promotor de l'MMTV. Aquí demostro que la màquinaria de remodelament reclutada és específicament BAF. Treballs anteriors van demostrar que la kinasa Msk1 és la responsable de la fosforilació de la serina 10 de la histona H3. En aquesta tesi es demostra que l'acetilació de la Lysina 14 de la histona H3 és essencial per l'activació del promotor, així com per l'anclatge de BAF. Després de l'expulsió dels dimers d'H2A/H2B, la unió d'NF1 al promotor és indispensable per estabilitzar la forma remodelada del nucleosoma. Per l'estudi en més detall de l'activació del promotor de l'MMTV he utilitzat el sistema de minicromosomes, mononucleosomes i tetràmers d'histones H3/H4 reconstituïts en seqüències salvatges i mutants del promotor de l'MMTV. He demostrat que, només quan un fragment de la seqüencia de l'MMTV està reconstituïda en tetràmers, el PR i l'NF1 poden estar units simultàniament a la seva seqüència de reconeixement en el promotor. També aporto evidències on es demostra que la unió d'NF1 al promotor facilita la posterior unió de més mol·lècules de PR als HREs interns (llocs 2 i 3) caracterizant en més detall el sinergisme funcional que existeix entre el PR i l'NF1 en aquestes condicions. / Evidence has been accumulating over the last few years pointing to the importance of chromatin structure and nucleosome positioning in cellular processes such as transcriptional regulation. Recent technological advances in the field have allowed the construction of detailed genome-scale maps of nucleosome positions, and there have been several attempts to define the sequence characteristics that guide the positioning of nucleosomes, the so-called "nucleosome code". In this thesis I give experimental evidence for the existence of a subset of very well-positioned nucleosomes in the human genome based on nucleosome-resolution tilling arrays and on deep sequencing of MNase-digested chromatin using the Solexa-Illumina platform. I show that these nucleosomes, which we have named "key nucleosomes", tend to occupy genomic locations of specific function, indicative of their special role. The DNA of these "key nucleosomes" exhibits a high symmetry of curvature, allowing their precise position on the human genome to be predicted in silico based on the structural attributes of the primary DNA sequence. The second part of this thesis provides new insights into the importance of chromatin organization and dynamics in the context of gene regulation. Steroid hormones induce transcription of their target genes by a complex mechanism requiring binding of the hormone receptors to hormone responsive elements (HREs) and the recruitment of a variety of coregulators. The Mouse Mammary Tumor Virus (MMTV) promoter has long been used as a model for the study of hormone receptormediated gene activation. It is known that progesterone receptor (PR) binds the exposed HRE1 of the MMTV promoter chromatin and recruits chromatin remodellers that catalyse ATP-dependent histone H2A/H2B displacement. I show that the ATP- ependent chromatin remodelling complex BAF, but not PBAF, is recruited after hormone treatment and is necessary for MMTV promoter activation. Along with the previously reported osphorylation of H3S10 by Msk, I show that an early PCAF- ediated acetylation of H3K14 is essential for the activation of the promoter by anchoring the BAF complex. Following transient displacement of H2A/H2B dimers, binding of NF1 is required for stabilizing the remodelled conformation of the MMTVnucleosome. To further study the activation process I have used MMTVminichromosomes, mononucleosomes and H3/H4 tetramer particles reconstituted on wild type MMTV and MMTV promoter fragments with point mutations disrupting binding of PR and NF1. I show that only when MMTV sequences are assembled on H3/H4 tetramer particles can PR bind to all five HREs while allowing NF1 access to its cognate site. Furthermore, I found that binding of NF1 facilitates access of PR to the central HREs 2 and 3, thus contributing to the reciprocal synergism between PR and NF1.
14

A unified approach to the emergence of complex communication

Corominas Murtra, Bernat 12 July 2011 (has links)
Aquesta tesi estudia l'emergència de complexitat en sistemes de comunicació naturals, prenent el llenguatge humà com a principal objecte d'estudi. Ens centrem en i) Patrons estadístics de complexitat, ii) Mecanismes generatius i iii) aspectes relacionats amb la teoria de la informació. Primer mostrem un estudi on es quantifica l'emergència de la sintaxi al nivell ontogenètic usant la moderna teoria de xarxes complexes. Posteriorment, es proposa un esquelet matemàtic per a la sintaxi humana amb el propòsit d'identificar les mínimes propietats formals d'un sistema generatiu, essent aquest constructe consistent amb els patrons observats prèviament. Seguidament explorem un patró molt comú en sistemes de comunicació complexes, la llei de Zipf, presentant un argument que explica la seva emergència des de consideracions únicament basades en la teoria de la informació. Finalment, abordem el problema de la referencialitat, proposant una mesura consistent amb la teoria de la informació que evalua el seu grau de conservació en un intercanvi comunicatiu arbitrari. / This dissertation studies the emergence of complexity in natural codes taking human language as the object of study. We focus our analysis in i) Statistical patterns of complexity, ii) Generative mechanisms and iii) Information theoretic aspects of complex communication. We first provide a quantitative identification of the emergence of syntax at the ontogenetic level through modern theory of complex networks. We then propose a mathematical backbone for human syntax with the aim to identify the minimal formal properties for a natural generative system, which is consistent with the previous observed patterns. We follow by studying a well-known statistical pattern of complex communication systems, Zipf's law, for which we propose an information-theoretic argument accounting for its emergence. Finally, the problem of referentiality is studied, proposing an information-theoretic estimator to evaluate its degree of conservation in a given communicative exchange.
15

Ecology of the marine copepod genus Oithona

Zamora Terol, Sara 29 September 2013 (has links)
Copepods have a crucial role in the pelagic marine ecosystem, for their participation in the nutrient cycling and carbon export in biogeochemical cycles, and their role as link organisms between primary producers and higher trophic levels. Historically, marine zooplankton studies have focused on large organism (> 1mm), due to the use of relatively large mesh sizes in plankton nets, which has resulted in an underestimation of the importance of small copepods such as the genus Oithona. The study of small copepods, and especiall of Oithona, has raised special interest in recent years due to its great abundance and ubiquitous presence in both coastal and oceanic regions, and with a distribution that extends from polar to tropical . Besides their numerical dominance, Oithona also makes up a significant fraction of the biomass of copepods in certain regions. Their described low metabolic rates, coupled with an ambush feeding behavior and low mortality, are considered the clue of their success and of their capacity to maintain active populations throughout the year. Although new insights on the ecology of Oithona have been acquired in the past decade, knowledge on their vital rates is still very scarce. The lack of studies on the ecophysiology of Oithona contrasts with the large amount of studies conducted on calanoid copepods on aspects related to feeding, growth, and egg production. The main objective of this thesis was to contribute to a better knowledge and understanding of some biological and ecological aspects of the genus Oithona. For that purpose, we carried out laboratory experiments with cultured specimens, and experimental lab and fieldwork with natural populations in polar and tropical regions. In the laboratory we studied the effect of food concentration on ingestion and fecundity rates of Oithona davisae. The results obtained indicate that Oithona davisae is able to feed at very low food concentrations, which indicates its ability to exploit oligotrophic environments. Oithona capacity to reproduce continuously throughout the year, even in environments or periods of low food availability, was confirmed by the relatively high fertility rates observed in laboratory experiments at low food concentrations. The trophic role of Oithona, their natural diet and ingestion rates were studied in different pelagic ecosystems; as well as the fecudity of adult females in these ecosystems, and their relationship with environmental factors. We also investigated some aspects of the population ecology Oithona in polar regions (abundance, vertical distribution and migration patterns). The results of the in situ investigations were carried out in order to compare life strategies between Oithona species of contrasting habitats. In polar environments, winter reproductive activity of the adult females was observed, which highlights the importance of small copepods in high-latitude environments, especially when large calanoid are not present in the productive zone of the water column. Moreover, the strategy of Oithona life in polar area is different from that of large calanoid, and it benefits from its independence from the spring blooms of phytoplankton to maintain active populations throughout the year. The ability of Oithona to successfully survive when unfavourable conditions are present in the water could explain the success of this genus of copepods in marine environments around the world.
16

Pharmacogenomic study of oppioid addicts in methadone treatment / Francina Fonseca Casals

Fonseca Casals, Francina 17 November 2010 (has links)
Although the well established efficacy of methadone maintenance treatment (MMT) in the opioid dependence disorder, there is a group of patients that are poor responders. The study of the influence of methadone pharmacodynamics and pharmacokinetics in dose requirements and program outcome remains still controversial. The aim of this dissertation is to study the pharmacodynamic and pharmacokinetic factors involved in the methadone maintenance treatment efficacy. The study recruited opioid dependence patients (DSM-IV criteria) from a MMT community program. Patients were clinically assessed and blood samples were obtained in order to evaluate methadone plasma concentrations of (R,S)-, (R) and (S)- methadone. Allelic variants of genes encoding the following proteins were assessed: BDNF, OPRM1, MYOCD, mGluR6, mGluR8, CRY1, NR4A2, 1q31.2 (rs965972), 2q21.2 (rs1867898), CYP3A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19 and P-glycoprotein. Responders and non-responders were defined by means of illicit opioid consumption detected in random urinalyses. Differences in response status were found depending on different single nucleotide polymorphisms (SNPs of genes encoding for BDNF, MYOCD and GRM6. The CYP2D6 metabolizing phenotype was associated with response to MMT, and also with methadone dosage requirement and methadone plasma concentrations. / Els programes de manteniment amb metadona (PMM) han demostrat eficàcia en el tractament del trastorn per dependència d'opiacis malgrat la persistència de pacients amb mala resposta al tractament. L'estudi dels factors farmacodinàmics i farmacocinètics implicats en la resposta terapèutica ofereix resultats controvertits. L'objectiu de la tesi doctoral que es presenta és estudiar els factors farmacodinàmics i farmacocinètics de la metadona que poden estar implicats en l'eficàcia del tractament. S'han inclòs pacients ambulatoris diagnosticats de trastorn per dependència d'opiacis (segons criteris DSM-IV) en PMM. Els pacients s'han avaluat a nivell clínic i s'han obtingut mostres de sang per a l'estudi de les concentracions plasmàtiques de (R,S)-, (R) i (S)- metadona. S'han estudiat també les variants al·lèliques dels gens que codifiquen per: BDNF, OPRM1, MYOCD, mGluR6, mGluR8, CRY1, NR4A2, 1q31.2 (rs965972), 2q21.2 (rs1867898), CYP3A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19 i P-glicoproteïna. La mostra s'ha dividit en responedors i no responedors en funció del nombre de controls d'orina positius per a heroïna en analítiques realitzades de forma aleatòria. Es van detectar diferències en resposta al tractament segons les variants dels gens codificants per a BDNF, MYOCD i GRM6. També es va detectar una associació entre el fenotip de CYP2D6, la resposta al tractament, la dosi requerida de metadona i les concentracions plasmàtiques.
17

Neurobiological mechanisms involved in MDMA-Seeking behaviour and relapse

Orejarena, Maria Juliana 06 September 2010 (has links)
(+) 3,4-metilendioximetanfetamina (MDMA), popularmente conocida como "éxtasis", es una droga susceptible de producir adicción en algunos individuos. Actualmente es consumida principalmente por adolescentes y jóvenes. Los particulares efectos psicoactivos inducidos por la MDMA, permiten distinguirlo de manera clara de otros psicoestimulantes o compuestos alucinógenos. Esta droga actúa principalmente activando el sistema dopaminérgico y serotonérgico en los circuitos neurales de placer. Sin embargo, los mecanismos neurobiológicos implicados en las propiedades adictivas de esta droga no han sido aún esclarecidos. El trabajo presentado en esta Tesis Doctoral ha puesto de manifiesto algunos aspectos claves de estos procesos que eran desconocidos hasta el momento. Hemos encontrado que el receptor de serotonina 5-HT 2A participa de forma critica en las propiedades reforzantes de la MDMA, contrario a lo observado en el caso de otros psicoestimulantes. Además, el bloqueo farmacológico de este receptor puede prevenir la reinstauración de la búsqueda de la MDMA, desencadenada por un estímulo o clave previamente asociado a su consumo. Estos efectos pueden ser debidos al bloqueo del control excitatorio que normalmente ejercen estos receptores sobre los niveles de dopamina en estructuras mesolímbicas, como ha sido revelado en nuestros estudios de microdiálisis. Hemos demostrado también que la MDMA puede actuar como clave interoceptiva y desencadenar la recaída a la búsqueda y consumo de cocaína. Adicionalmente, nuestros estudios han mostrado que tanto la activación del sistema dopaminérgico mesolímbico, como los cambios en la expresión génica en diferentes ´areas cerebrales que ocurren tras la administración de la MDMA, dependen de si el sujeto participa de manera activa en el consumo de esta droga, o si por el contrario la recibe de forma pasiva. En conclusión, este trabajo resalta la importancia de los procesos de aprendizaje y memoria sobre las propiedades reforzantes/recompensantes de la MDMA. Además, nuestras investigaciones aportan nuevas evidencias en relación a la participación del sistema serotonérgico en la búsqueda y recaída al consumo de esta droga. / (+) 3,4-methylenedioxymethamphetamine (MDMA), commonly known as "ecstasy", is currently a highly consumed drug with liability to produce addiction in some individuals. MDMA induces unique psychoactive effects that clearly distinguish it from hallucinogenic or psychostimulant drugs. MDMA mainly enhances the activity of both the serotonergic and the dopaminergic system in the esolimbic brain reward pathways. However, the neurobiological mechanisms underlying its possible addictive properties are still not fully understood. In the present work, we have contributed to this subject by establishing that the serotonin 5-HT2A receptor, in contrast to what has been observed for other drugs of abuse, is critical for MDMA-induced reinforcement. Moreover, the pharmacological blockade of this receptor can prevent cue-induced relapse. This effect is possibly mediated by its excitatory control over basal and MDMA-induced increase in midbrain dopamine, as supported by our microdialysis data. Furthermore, we have also shown that MDMA can act as an interoceptive cue to induce relapse to cocaine-seeking behaviour. Additionally, we demonstrated differential changes at the level of the dopaminergic brain reward pathway and gene expression changes in different brain areas, following self-administeredMDMAin comparison to passive administration. These results underpin the impact of a learning component in the rewarding/reinforcing properties of MDMA, and provide new evidence for the serotonergic involvement in MDMA-seeking behavior and relapse.
18

Utilidad de la ecografia en modo B y de la ecografia Doppler-Duplex color en la biopsia de las lesiones óseas y de tubo digestivo

Marco Doménech, Santiago F. 08 October 2003 (has links)
Exponer nuestra experiencia realizando biopsias percutáneas guiadas por ecografía en lesiones óseas y del tubo digestivo.Evaluar el papel y la utilidad de las biopsias percutáneas guiadas por ecografía en el diagnóstico de lesiones del tubo digestivo, cuando la lesión no es alcanzable por el endoscopio pero sea fácilmente visible por ecografía. La biopsia percutánea de las lesiones óseas es ampliamente utilizada como método diagnóstico, utilizando la radioscopia o la tomografía computerizada como guía de biopsia. Nosotros en esta tesis describimos el uso de la ecografía como guía de biopsia percutánea en lesiones óseas.MATERIAL Y MÉTODOS:Hemos realizado 198 biopsias ( 197 biopsias percutáneas y una quirúrgica ) en 193 pacientes. La biopsia percutánea fue realizada bajo guía ecográfica en 167 pacientes y bajo radioscopia en 30 casos. La localización de las lesiones fueron el tubo digestivo, hueso y algunas en otras localizaciones como tórax, hígado o tiroides.Realizamos 42 biopsias en 41 pacientes entre 14 y 81 años de edad ( media de 57,5 años ). Las lesiones se mostraron como un ¨pseudoriñón¨ en 27 casos y como una masa en los otros 15 casos. Las biopsias se realizaron bajo guía ecográfica en tiempo real, usando una compresión gradual y con un transductor de 3,5-5Mhz. En 39 biopsias obtuvimos un cilindro para estudio histológico con una aguja automática de 18G y en 32 de estos casos obtuvimos una aspiración con aguja fina de 22G en 28 casos y con una de 21G en los otros cuatro casos. En otros tres casos usamos una técnica coaxial con una aguja de 20G y otra de 22G para la citología.Utilizamos la biopsia percutánea guiada por ecografía en 65 biopsias de lesiones óseas en 63 pacientes ( 30 hombres y 33 mujeres ). El rango de edad estaba entre 1 y 82 años y la media de edad en 47,2 años. Las lesiones se dividieron en cuatro categorías: 41 lesiones eran líticas con masa de partes blandas, 14 eran líticas sin masa de partes blandas, 4 líticas con cortical íntegra y 6 lesiones esclerosas. Utilizamos distintas técnicas de biopsia para cada grupo de lesiones.RESULTADOS:En el tubo digestivo, obtuvimos un diagnóstico en el 95,2% ( 40 / 42 ) de las biopsias con aguja gruesa y en el 45,7% ( 16 / 35 ) de las biopsias con aguja fina. Las lesiones estaban entre la faringe y el colon sigmoide. Los pacientes tenían lesiones malignas en 28 casos y benignas en 13. Solo hubo una complicación que consistió en un bilioperitoneo.En las biopsias óseas, con el estudio citológico obtuvimos un diagnóstico en 50 casos ( 76,9% ), con la histología en 56 casos ( 86,1% ) y combinando ambas técnicas en 60 casos ( 92,3% ). En ningún caso hubo complicaciones.CONCLUSIONES:La biopsia percutánea guiada por ecografía es una técnica útil y segura para diagnosticar lesiones del tubo digestivo que pueden verse en ecografía y no sean accesibles endoscópicamente.La ecografía es una técnica segura y eficaz para guiar las biopsias de lesiones óseas porque pueden identificar cambios sutiles en la cortical así como el componente de partes blandas asociado. / To expose our experience performing sonography guided percutaneous biopsy of skeletal and gastrointestinal lesions.To evaluate the role and safety of ultrasound guided percutaneous biopsy in the diagnosis of digestive tract lesions, when the lesions are not suitable to biopsy by endoscopy and safely reachable by ultrasound.Percutaneous biopsy of skeletal lesions is a widely used diagnostic technique that involves fluoroscopìc or computerized tomography guidance. In this report we describe the use of ultrasonography ultrasound in the guidance of percutaneous biopsy in skeletal lesions.MATERIALS AND METHODS:We performed 198 biopsies ( 197 percutaneous biopsies and one surgical biopsy ) in 193 patients. The percutaneous biopsy was performed under sonographic guidance in 167 cases and under fluoroscopic guidance in 30 cases. The location were bone, gastrointestinal tract and other locations as chest, liver or thyroid gland. We performed 42 biopsies in 41 patients aged 14-81 years (mean 57.5 years ). The lesions showed a pseudokidney sign in 27 cases and mass appearance in the remaining 15 cases. Biopsies were carried out under real-time US guidance using graded compression, with a 3,5-5 MHz microconvex transducer. In 39 biopsies core specimens were obtained with an 18G automatic needle gun; in 32 of these cases fine needle aspiration biopsy was obtained with a 22G needle in 28 cases and with a 21G in the other 4 cases. In the remaining 3 cases a coaxial technique with 20G and 22G for cytology were used. We employed sonography to guide percutaneous biopsy in 65 skeletal lesions in 63 patients (30 male and 33 female). Age ranged 1-82 year. Mean 47.2. The lesions were grouped into four categories: 41 were lytic with soft tissue mass, 14 lytic with disrupted cortical without soft tissue mass, 4 lytic with intact cortical and 6 sclerotic. Different techniques and materials were used in each group.RESULTS:In gastrointestinal tract, in 95,2 % ( 40 / 42 ) of core biopsies performed a specific diagnosis was obtained. A positive diagnosis was obtained in 45,7% ( 16 / 35 ) of fine needle aspirations. The lesions were localized from pharynx to the sigmoid colon. The patients had malignant lesions in 28 cases and benign in 13 cases. Only one serious complication, bile peritonitis, was observed. In skeletal biopsies, cytological assessment obtained the diagnosis in 50 cases, (success rate of 76.9%), histology in 56 cases ( 86.1% ) and combining both in 60 cases ( 92.3% ). There were not complicationsCONCLUSION:Percutaneous biopsy under sonography guidance can be used safely and efficiently to diagnose digestive tract lesions which can be visualized on US and which are not accesible endoscopically.Ultrasouund is a highly accurate and safe method of guidance in percutaneous biopsy of bone lesions because can identify subtle changes in the cortical and the associated soft tissue component.
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Development of xenobiotic-free conditions towards the generation and propagation of clinically-safe human pluripotent stem cells

Rodríguez Pizà, Ignasi 05 July 2010 (has links)
Les cèl·lules mare embrionàries humanes (hESC) i més recentment les cèl·lules de pluripotència induïda (iPSC) representen una oportunitat sense precedents per al desenvolupament de noves estratègies terapèutiques per malalties degeneratives humanes. Així mateix, la possibilitat d'obtenir iPSC específiques de pacient obre la porta per l'establiment de models de malaltia genuïnament humans. Una de les limitacions que dificulta l'aplicació clínica de les cèl·lules pluripotents és que la seva obtenció es du a terme a l'actualitat amb medis i reactius que contenen fonts proteiques d'origen animal (xenobiòtics). Aquesta tesis contribueix al desenvolupament de protocols de derivació i de cultiu de hESC, que les apropa a la seva utilització clínica. A més hem desenvolupat estratègies basades en iPSC més segures i eficaces per al tractament de malalties humanes. / Human embryonic stem cells (hESC) and, more recently, induced pluripotent cells (iPSC) represent a new and unprecedented opportunity for the development of new therapeutic strategies for human degenerative diseases. The possibility to derive patient specific iPSC opens the door to he establishment of disease models exquisitely human. One of the limitation that, concretely, limits the clinic application of pluripotent cells is the fact that their derivation, currently, is obtained with media and reagents which contain animal proteic sources (xenobiotics). This thesis contributes to the development of protocols of derivation and culture of hESC that bring them closed to a clinical application. Moreover, we have developed iPSC-based strategies that are both safer and more effective for the treatment of human diseases.
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Full characterization of the small RNA transcriptome using novel computational methods for high-throughput sequencing data: study of miRNA variability in eukaryote organisms.

Pantano Rubiño, Lorena 26 September 2011 (has links)
In this thesis we have developed a user-friendly tool, SeqBuster, for the analysis of small RNA (sRNA) data generated by next generation sequencing strategies, with special emphasis on deep characterization of miRNA variants (isomiRs). We tested the tool using public datasets, revealing an unexpected amount of isomiRs in the total miRNA profile in different species. In addition, we detected all known classes of non-miRNA sRNAs and new sRNAs with a still unassigned function. Furthermore, we studied the implication of miRNAs and isomiRs in human brain development and aging and in Huntington disease, concluding that miRNAs/isomiRs may contribute to central nervous system physiological and pathological conditions. Overall, our results have uncovered a new layer of complexity in miRNAs, with probable consequences in mRNA mediated gene expression regulation underlying different biological functions. Furthermore SeqBuster may be extremely useful to identify sRNA sequences with a putative regulation role in selective biological processes / En esta tesis hemos desarrollado una herramienta, SeqBuster, para el análisis de datos de RNA (sRNA) de pequeño tamaño generados por las nuevas tecnologías de secuenciación, con especial énfasis en la caracterización de variantes de los miRNAs. Aplicamos la herramienta a datos públicos de secuenciación, lo que reveló una inesperada abundancia de isomiRs en diferentes especies. Ademas, detectamos todas las clases conocidas de otros sRNAs y de nuevos sRNAs con funciones desconocidas. También estudiamos la implicación de los miRNAs e isomiRs en el desarrollo y envejecimiento del cerebro humano, y en la enfermedad de Huntington. Nuestros resultados resaltan una posible importancia de la plasticidad de secuencia de los miRNAs, con probables consecuencias en la regulación de la expresión génica, subyacente a varias funciones biológicas. Por último, SeqBuster, podría ser extremadamente útil para identificar nuevos sRNAs con una posible función en determinados procesos biológicos.

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