Global ETD Search

1	Korelace molekulárně-genetických a morfologických znaků vzácných nádorů slinných žláz / Correlation of Molecular-Genetic and Morphological Markers of Rare Salivary Gland Tumors Šteiner, Petr January 2018 (has links) Thesis deals with relationship between histomorphological and molecular-genetic findings of selected salivary gland tumors. Author, as a molecular-cytogeneticist mainly focused on detection of tumor-specific translocations of the salivary gland tumors which can serve as differential diagnostic markers. The thesis is composed as a commented files of authors own publications, and it is divided into four parts. First part deepens the knowledge of salivary adenoid cystic carcinoma. It was proved, that t(6;9)(q22-23;p23-24) resulting in fusion of transcription factors MYB-NFIB, or more rarely t(8;9) resulting in MYBL1-NFIB fusion represent robust differential diagnostic marker of adenoid cystic carcinoma. Further it was proved, that the 1p36 deletion can serve as an unfavorable prognostic indicator of adenoid cystic carcinoma, as the patients with 1p36 deletion had significantly lower survival. Second part summarizes new developments about mammary analogue secretory carcinoma (MASC), which was described by our group as a new salivary tumor entity characterized by translocation t(12;15)(p13;q25) resulting in ETV6-NTRK3 fusion. Another novel observation is a discovery of ETV6-RET fusion in a subset of MASC cases. Further, the first two MASCs of nasal mucosa origin have been described. Third part consists...
2	Korelace molekulárně-genetických a morfologických znaků vzácných nádorů slinných žláz / Correlation of Molecular-Genetic and Morphological Markers of Rare Salivary Gland Tumors Šteiner, Petr January 2018 (has links) Thesis deals with relationship between histomorphological and molecular-genetic findings of selected salivary gland tumors. Author, as a molecular-cytogeneticist mainly focused on detection of tumor-specific translocations of the salivary gland tumors which can serve as differential diagnostic markers. The thesis is composed as a commented files of authors own publications, and it is divided into four parts. First part deepens the knowledge of salivary adenoid cystic carcinoma. It was proved, that t(6;9)(q22-23;p23-24) resulting in fusion of transcription factors MYB-NFIB, or more rarely t(8;9) resulting in MYBL1-NFIB fusion represent robust differential diagnostic marker of adenoid cystic carcinoma. Further it was proved, that the 1p36 deletion can serve as an unfavorable prognostic indicator of adenoid cystic carcinoma, as the patients with 1p36 deletion had significantly lower survival. Second part summarizes new developments about mammary analogue secretory carcinoma (MASC), which was described by our group as a new salivary tumor entity characterized by translocation t(12;15)(p13;q25) resulting in ETV6-NTRK3 fusion. Another novel observation is a discovery of ETV6-RET fusion in a subset of MASC cases. Further, the first two MASCs of nasal mucosa origin have been described. Third part consists...
3	Mecanismes moleculars en el transtorn de la conducta alimentària: estudis en humans i en model murins Mercader Bigas, Josep Maria 11 July 2008 (has links) Els trastorns de la conducta alimentària (TCA) tenen una etiologia complexa en la que hi intervenen factors de predisposició socioculturals, ambientals i genètics. S'ha aprofundit en les bases moleculars dels TCA mitjançant estudis en pacients i en models murins. S'ha descrit una alteració en la concentració de BDNF en plasma de pacients, una correlació d'aquests nivells amb trets psicopatològics, i una associació de determinats polimorfismes a bulímia nerviosa i als nivells de BDNF en plasma. Un estudi d'associació en vàries poblacions ha demostrat una forta associació de variants del gen NTRK3, amb epistasi amb NGF, a TCA. Un model de sobreexpressió de BDNF confirma el seu paper en la regulació del pes corporal i estableix un possible vincle entre BDNF i la fisiopatologia de les tremolors. La caracterització del ratolí anx/anx suggereix que pot ser un model de la síndrome caquètica que acompanya malalties com el càncer, la SIDA o les malalties autoimmunitàries. / Eating disorders (ED) are complex disorders were environmental, sociocultural and genetic factors are involved. We have improved the knowledge of the genetic basis of ED through studies involving ED patients and murine models. Altered BDNF blood levels have been linked to ED and its related psychopathological traits. In addition several polymorphisms in the BDNF gene have been associated to bulimia nervosa and BDNF plasma levels. A family based association study has shown a strong association of NTRK3 variants to ED which show epistasis with NGF. The generation of an overexpression mouse model for BDNF confirms its role in body weight regulation and establishes a possible link between BDNF and the pathophysiology of tremors. The characterization of the anx/anx mouse model suggests that it may be a good model for the cachexia syndrome that accompanies certain chronic or inflammatory diseases such as cancer, AIDS or autoimmune diseases. microarray miRNAs transcriptoma hypothalamus cachexia feeding regulation anx/anx NGF NTRK3 SNPs psychopathology neurotrophin BNDF bulimia nervosa anorexia nervosa eating disorders microarray miRNAs transcriptoma hipotàlem caquèxia regulació de ingesta anx/anx NGF NTRK3 neurotrofines BDNF SNPs psicopatologia bulímia nerviosa anorèxia nerviosa trastorns de la conducta alimentària 57 577 61
4	Analysis of genetic variation in microrna-mediated regulation and the susceptibility to anxiety disorders Muiños Gimeno, Margarita 18 December 2009 (has links) We have investigated genetic variation in microRNA-mediated regulation as a susceptibility factor for anxiety disorders following two different approaches. We first studied two isoforms of the candidate gene NTRK3 by re-sequencing its different 3'UTRs in patients with Panic (PD) and Obsessive Compulsive disorders (OCD) as well as controls. Two rare variants that altered microRNA-mediated regulation were identified in PD. Conversely, association of a common SNP with OCD hoarding subtype was found. Moreover, we have also studied a possible involvement of microRNAs in anxiety disorders. Consequently, we have analysed the genomic organisation and genetic variation of miRNA-containing regions to construct a panel of SNPs for association analysis. Case-control studies revealed several associations. However, it is worth remarking the associations of miR-22 and miR-488 with PD; two microRNAs for which functional assays and transcriptome analysis after microRNA overexpression showed significant repression of a subset of genes involved in physiological pathways linked to PD development. / Hem investigat la variació genètica a la regulació mediada per microRNAs com a factors de susceptibilitat pels trastorns d'ansietat seguint dues aproximacions diferents. Primer vam estudiar dues isoformes del gen candidat NTRK3 mitjançant la reseqüenciació dels seus diferents 3'UTRs a pacients de pànic (TP), a pacients amb trastorn obsessiu compulsiu (TOC) i a controls. Dues variants rares que alteren la regulació mediada per microRNAs foren identificades per TP. D'altra banda, es trobà associació d'un SNP comú amb el subtipus acumulador de TOC. A més, també hem estudiat la possible implicació dels microRNAs als trastorns d'ansietat. Conseqüentment, hem analitzat l'organització genòmica i la variació genètica a regions que contenen microRNAs per construir un panell d'SNPs per fer anàlisis d'associació. Els estudis cas-control van revelar algunes associacions. Tanmateix, val la pena destacar les associacions del miR-22 i el miR-488 amb TP; dos microRNAs pels quals assajos funcionals i anàlisis de transcriptoma després de la seva sobreexpressió han mostrat una repressió significativa d'un grup de gens implicats en vies fisiològiques lligades al desenvolupament del TP. isoforma anàlisi de transcriptoma PCR assaig de luciferasa variant comuna variant rara reseqüenciar estudis d'associació poly-miRTS trastorn obsessiu-compulsiu trastorn de pànic trastorn d'ansietat variació genètica intraespecífica SNP NTRK3 gen candidat element regulador microRNA variació genòmica desordres poligènics trets complexes isoform transcriptome analysis PCR luciferase assay common variant rare variant re-sequencing association studies poly-miRTS obsessive-compulsive disorder panic disorder anxiety disorder genetic variation within species SNP NTRK3 candidate gene regulatory element microRNA genome variation polygenic disorders complex traits 57
5	Micro RNA-Mediated regulation of the full-length and truncated isoforms of human neurotrophic tyrosine kinase receptor type 3 (NTRK 3) Guidi, Mònica 13 January 2009 (has links) Neurotrophins and their receptors are key molecules in the development of thenervous system. Neurotrophin-3 binds preferentially to its high-affinity receptorNTRK3, which exists in two major isoforms in humans, the full-length kinaseactiveform (150 kDa) and a truncated non-catalytic form (50 kDa). The twovariants show different 3'UTR regions, indicating that they might be differentiallyregulated at the post-transcriptional level. In this work we explore howmicroRNAs take part in the regulation of full-length and truncated NTRK3,demonstrating that the two isoforms are targeted by different sets of microRNAs.We analyze the physiological consequences of the overexpression of some of theregulating microRNAs in human neuroblastoma cells. Finally, we providepreliminary evidence for a possible involvement of miR-124 - a microRNA with noputative target site in either NTRK3 isoform - in the control of the alternativespicing of NTRK3 through the downregulation of the splicing repressor PTBP1. / Las neurotrofinas y sus receptores constituyen una familia de factores crucialespara el desarrollo del sistema nervioso. La neurotrofina 3 ejerce su funciónprincipalmente a través de una unión de gran afinidad al receptor NTRK3, del cualse conocen dos isoformas principales, una larga de 150KDa con actividad de tipotirosina kinasa y una truncada de 50KDa sin dicha actividad. Estas dos isoformasno comparten la misma región 3'UTR, lo que sugiere la existencia de unaregulación postranscripcional diferente. En el presente trabajo se ha exploradocomo los microRNAs intervienen en la regulación de NTRK3, demostrando que lasdos isoformas son reguladas por diferentes miRNAs. Se han analizado lasconsecuencias fisiológicas de la sobrexpresión de dichos microRNAs utilizandocélulas de neuroblastoma. Finalmente, se ha estudiado la posible implicación delmicroRNA miR-124 en el control del splicing alternativo de NTRK3 a través de laregulación de represor de splicing PTBP1. RISC complex retinoic acid renilla luciferase real-time quantitative PCR PTBP1 pri-miRNA pre-miRNA post-transcriptional regulation piRNA PicTar pGL4.13 PCR P-body p75NTR overexpression NTRK3 NTRK2 NTRK1 non-coding RNAs NGF neurotrophin neurotrophic signaling neuronal differentiation neurodevelopment neuroblastoma nervous system mRNA miRNA target prediction miRNA profiling miRNA mimic miRNA microarray miRNA inhibitor miRanda microRNA microarray luciferase assay Ingenuity Pathway Analysis (IPA) heLa cells gene silencing gene regulation full-length isoform (FL-NTRK3) firefly luciferase ERK disease dicer cancer development BDNF argonaute alternative splicing 3'UTR RNAhybrid RT-PCR SH-SY5Y cells siRNA standard error synaptic plasticity target validation TargetScan transfection translational repression TrkA TrkB TrkC truncated isoform (TR-NTRK3) tyrosine kinase (TK) western blot 575 61

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