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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.
1

Identifying Barriers to Enrollment of Diverse Populations in Arizona Following the Initial Open Enrollment Period of the Affordable Care Act

Moseley, Joseph 06 June 2017 (has links)
A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / While it is known that over 266,000 Arizonans enrolled in health coverage through the federal Marketplace and Medicaid from October 2013 through May 2014, little analysis has been performed to examine whether enrollment by diverse racial and ethnic groups sufficiently reduced disparities in coverage. We obtained publicly available data from the Census Bureau comparing rates of uninsured by race/ethnicity from 2013 to 2014 in Arizona from the American Community Survey. The uninsured rate in Arizona for the total civilian no institutionalized population dropped from 17% in 2013 to 13.6% in 2014. The uninsured rate in Arizona for whites declined from 15.7% to 12.2%, for African Americans declined from 17.4% to 11.1%, for American Indian/Alaskan Natives declined from 26.9% to 24.1%, for Asian Americans declined from 15.1% to 11.0% and for Hispanic/Latino declined from 27.5% to 22.2%. We conducted interviews with nine community organizations in order to identify barriers that must be addressed moving forward to lessen insurance coverage disparities among various minority groups. Technological literacy and functionality, lack of funding, lack of personnel, physical vastness of many populations, language, and cultural differences were commonly identified as barriers to enrollment. Mistrust of government and confusion regarding the specific provisions within the ACA pertaining to Native individuals were also cited.
2

Analyse structurale et fonctionnelle des particules sRNP à boîtes H/ACA, catalysant la formation ciblée des pseudouridines dans les ARN d'archaea / Structural and functional analysis of box H/ACA sRNP particles, which catalyze the targeted formation of pseudouridines in archaeal RNAs

Fourmann, Jean-Baptiste 13 November 2009 (has links)
L’isomère de l’uridine (U), la pseudouridine (?), est le nucléoside le plus fréquemment rencontré dans les ARN. La réaction de pseudouridylation dans les ARN est catalysée par des ARN:?-synthases qui, soit fonctionnent comme des enzymes protéiques, soit sont portées chez les eucaryotes et les archaea par des particules ribonucléoprotéiques (RNP). Chaque RNP est composée d’un RNA guide dit à boîtes H/ACA (sno/sca/sRNA chez les eucaryotes et sRNA chez les archaea) et d’un ensemble invariable de protéines : l’enzyme ARN:?-synthase Dyskérine/aCBF5 et les 3 protéines NOP10/aNOP10, GAR1/aGAR1 et NHP2/L7Ae. L’ARN guide assure la reconnaissance de l’ARN cible à modifier par appariement de bases. Les sRNA H/ACA identifiés chez l’archae Pyrococcus abyssi ont servi de modèles pour des études de structure-fonction basées sur i) la mesure de l’activité de sRNP H/ACA reconstituées avec les composants protéiques et nucléiques purifiés, ii) l’analyse de la structure 2D des ARN au sein des RNP par des sondes chimiques et enzymatiques et par dichroïsme circulaire, iii) les diverses structures 3D disponibles. Les déterminants moléculaires présents sur les ARN guides ont été précisés, ainsi que le rôle fonctionnel des différentes protéines, de leurs domaines structuraux et de résidus conservés. Nous montrons que l’association entre aNOP10 et L7Ae est cruciale pour l’activité des RNP. Nous avons identifié que aCBF5 pouvait catalyser la formation des résidus ?55 dans les ARNt et ?2603 dans l’ARN 23S sans l’intervention de sRNA. Nous avons étudié le rôle de résidus conservés de aNOP10 ainsi que du site actif et de la boucle ß7/ß10 de aCBF5 dans les activités guidée et non guidée de aCBF5. / Pseudouridine (?), uridine’s isomer, is the most abundant modified nucleoside found in structured RNAs. The reaction of pseudouridylation is either catalyzed by a limited number of standalone RNA:?-synthases, or in eukaryotes and archaea by multiple ribonucleoprotein particles (the so-called, box H/ACA sno/sca/sRNPs). Each RNP is composed of a specific box H/ACA RNA used as a guide to define the U residue for modification, and a common set of four proteins– the RNA:?-synthase Dyskerin/aCBF5, and the auxiliary proteins NOP10/aNOP10, GAR1/aGAR1, NHP2/L7Ae (respectively in human and archaea). Initially, 7 guide RNAs were identified in the archaeon P. abyssi, which were used as models for structure-function analyses. Activities of RNPs reconstituted with purified protein and RNA components were measured; RNA 2D structure within RNPs was investigated by chemical and enzymatic probing assays as well as by circular dichroism. By taking into consideration the various 3D structures recently resolved, we were able to pinpoint the RNA molecular determinants and to clarify the role played by each protein, their domains, and some of their conserved residues. Hence, interaction between aNOP10 and L7Ae was found to be crucial for RNP activity. Moreover, we show that the enzyme aCBF5 catalyzes pseudouridylation at the position 55 in tRNAs and the position 2603 in 23S rRNA without the use of any guide sRNA. The role of residues conserved in aNOP10, and in the active site and the ß7/ß10 loop of aCBF5 for the RNA and non-RNA guided activities were analyzed.
3

Evolution of Physician-Centric Business Models Under Patient Protection and Affordable Care Act

Nix, Tanya J. 01 January 2014 (has links)
For several decades, the cost of medical care in the United States has increased exponentially. Congress enacted the Patient Protection and Affordable Care Act (PPACA) of 2010 to ensure affordable healthcare to the citizens of the United States. The purpose of this case study was to explore physicians' perspectives regarding physician-centric business models evolving under the requirements of PPACA legislation. Complex adaptive systems formed the conceptual framework for this study. Data were gathered through face-to-face, semistructured interviews and e-mail questionnaires with a purposeful sample of 20 participants across 14 medical specialties within Northeast Texas. Participant perceptions were elicited regarding opinions of PPACA legislation and the viability of business models under the PPACA. In addition, a word cloud was used to identify 3 prevalent or universal themes that emerged from participant interviews and questionnaires, including (a) use of mid-level practitioners, (b) changes to provider practices, and (c) lack of business education. The implications for positive social change include the potential to develop innovative models for the delivery of medical care that will improve the health of the aggregate population. Healthcare leaders may use the findings to advance the evolution of physician business models that meet the needs of healthcare stakeholders. These findings may also inform healthcare leaders of the need to develop cost-effective and innovative organizational models that are distinct to individual patient populations.
4

Perfil epidemiol?gico, cl?nico e terap?utico da insufici?ncia card?aca em um hospital de refer?ncia no Vale do Jequitinhonha-MG, Brasil / Epidemiological, clinical and therapeutic profile of heart failure in a referral hospital in the Vale do Jequitinhonha-MG, Brazil

Soares, Fabiana Fernandes Rego 08 August 2013 (has links)
?rea de Concentra??o: Interdisciplinar. / Submitted by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2015-01-09T13:42:50Z No. of bitstreams: 2 fabiana_fernandes_rego_soares.pdf: 1999916 bytes, checksum: cd80d918d118b5451b6f5464a5e3e2ac (MD5) license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2015-01-09T13:43:29Z (GMT) No. of bitstreams: 2 fabiana_fernandes_rego_soares.pdf: 1999916 bytes, checksum: cd80d918d118b5451b6f5464a5e3e2ac (MD5) license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2015-01-09T13:43:44Z (GMT) No. of bitstreams: 2 fabiana_fernandes_rego_soares.pdf: 1999916 bytes, checksum: cd80d918d118b5451b6f5464a5e3e2ac (MD5) license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) / Made available in DSpace on 2015-01-09T13:43:44Z (GMT). No. of bitstreams: 2 fabiana_fernandes_rego_soares.pdf: 1999916 bytes, checksum: cd80d918d118b5451b6f5464a5e3e2ac (MD5) license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) Previous issue date: 2013 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (Capes) / Funda??o de Amparo ? Pesquisa do estado de Minas Gerais (FAPEMIG) / As doen?as cr?nicas n?o transmiss?veis constituem a principal causa de mortalidade em todo o mundo e t?m aumentado em ritmo acelerado. Elevadas taxas de interna??o e re-interna??o hospitalares causadas pela descompensa??o cl?nica da insufici?ncia card?aca t?m sido descritas e representam um grande problema. O objetivo deste estudo foi conhecer as caracter?sticas cl?nicas, epidemiol?gicas e terap?uticas das interna??es devido ? Insufici?ncia Card?aca em um hospital do interior de Minas Gerais. Realizou-se o estudo quantitatitativo, descritivo e observacional de 391 prontu?rios de interna??es pelo SUS devido a Insufici?ncia Card?aca, no per?odo de 2 anos. Foram realizadas an?lises de estat?stica descritiva utilizando-se do software Statistical Package for Social Science (SPSS) para obten??o de m?dia e mediana dos dados coletados. O n?vel de signific?ncia adotado foi de 95% (p<0,050). Os resultados demonstraram que a m?dia de idade foi de 67,75 anos ?15,5, sendo 51,2% do sexo feminino. Dentre as comorbidades: 77,0% apresentaram Hipertens?o Arterial Sist?mica, 19,7% Diabetes e 30,3% Chagas. A frequ?ncia de infarto do mioc?rdio pr?vio foi de 10,3%. A principal queixa identificada foi dispn?ia (81,6%). A m?dia do tempo de interna??o foi de 6,23 dias, e o custo m?dio de R$ 1.202,78. A taxa de mortalidade foi de 12,5%. N?o houve associa??o estatisticamente representativa entre ?bito e as vari?veis sexo, comorbidades e quantidade de doen?as. Os principais medicamentos prescritos foram: anticoagulantes 104,60%, diur?ticos 81,84% e digit?licos 53,19%. O uso de inibidor da ECA e ?-bloqueador foram inferiores ao recomendado nas diretrizes. Apenas 26,6% (n=104) chegaram ao hospital com um documento de refer?ncia e 39,9% (n=156) receberam algum tipo de encaminhamento ao sair de alta. Dentre as interna??es hospitalares a maior propor??o foi de mulheres com idade avan?ada e muitas comorbidades associadas. A an?lise dos resultados demontra que h? possibilidade de aperfei?oar a qualidade da assist?ncia oferecida contribuindo para melhoria na qualidade de vida, diminui??o do n?mero de hospitaliza??es, dos custos e refletir positivamente na redu??o da taxa de mortalidade no ambiente hospitalar. / Disserta??o (Mestrado Profissional) ? Programa de P?s-Gradua??o em Sa?de, Sociedade e Ambiente, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2013. / ABSTRACT The non- transmissible chronic diseases are the leading cause of mortality around the world and have been increasing at a rapid pace. High rates of hospitalization and re-hospitalization caused by hospital clinical decompensation of heart failure have been described and represent a major issue. The aim of this study was getting to know the characteristics of the clinical, epidemiological and therapeutic hospitalizations due to heart failure in a hospital in Minas Gerais. We carried out a study of the quantitative, observational and descriptive records about 391 SUS admissions due to heart failure, in the period of 2 years. It was hold analysis including descriptive statistics using the Statistical Package for Social Science (SPSS) to obtain mean and median rates of the data collected. The significance level applied was 95% (p <0.050). The results showed that the average age was 67.75 ? 15.5 years, 51.2% of them, female. Among the comorbidities: 77.0% had systemic hypertension, 19.7% had Diabetes wounds and 30.3% had Chagas disease. The frequency of before myocardial infarction was 10.3%. The main complaint identified was dyspnea (81.6%). The average length of stay was 6.23 days and the average cost of R$ 1202,78. The mortality rate was 12.5%. There wasn?t a representative association between death and the variables gender, comorbidities, and number of diseases. The main drugs prescribed were: 104.60% anticoagulants, diuretics 81.84% and digitalis 53.19%. The use of ACE inhibitors and ?-blocker were lower than the recommended guidelines. Only 26.6% (n = 104) of the patients arrived at the hospital with a reference document and 39.9% (n = 156) of them received some type of referral to leave the hospital. The highest proportion among hospital admissions was women with advanced age and lots of comorbidities. The results showed that it is possible to improve the quality of care offered contributing to improved quality of life, decrease the number of hospitalizations, costs and have a positive impact in reducing the mortality rate in the hospital environment.
5

STRUCTURAL AND FUNCTIONAL CHARACTERIZATION OF ARCHAEAL BOX H/ACA RIBONUCLEOPROTEIN INVOLVED IN RIBOSOMAL RNA PSEUDOURIDYLATION

MAJUMDER, MRINMOYEE 01 December 2013 (has links)
Ribosomal RNAs (rRNA) undergo several post-transcriptional modifications inside the cell. These modifications can be (1) RNA- independent (enzyme only) and (2) guide RNA-mediated. In the latter mechanism, a group of small, metabolically stable, non-coding RNAs, present as ribonucleoprotein (RNP) particles, modify ribosomal RNAs inside the cell. One of the highly abundant rRNA modifications is pseudouridine (Y) formation. In Archaea and Eukarya, pseudouridine synthases, with the help of small RNAs, form pseudouridines at functionally important regions in rRNA. Cbf5, the pseudouridine synthase, three other core proteins, and a box H/ACA RNA form the ribonucleoprotein complex in sRNP-mediated rRNA pseudouridylation. Certain Ys in rRNAs are evolutionarily conserved from Bacteria to human. Among those, two Ys are present in helix 69 of rRNA and one in helix 90. We successfully deleted Cbf5 in Haloferax volcanii, a haloarchaeon, and showed that the deleted strain was viable. It was the first report where Cbf5 deletion was achieved, because deletion or mutation of cbf5 or of its homologs is lethal in eukaryotes. We also found that the cbf5 deleted strain was unable to produce the three highly conserved Ys in rRNA of H. volcanii (position 1940, 1942 in helix 69, and 2605 in helix 90), whereas the tRNA Ys were intact. To identify the specific structural features of Cbf5 involved in rRNA Ψ formation, we used a cbf5 deleted strain which was complemented with a plasmid borne copy of the gene. Using the crystal structure of Pyrococcous furiosus Cbf5 as template, we created a homology model of H. volcanii Cbf5 (HvCbf5) and identified several residues and motifs/domains of HvCbf5 that might be important to the protein's enzymatic activity. By using an in vivo mutational approach, we confirmed some previously predicted and certain unidentified residues/motifs/domains that serve as positive determinants of rRNA Ys1940, 1942, and 2605 formation inside the cell. A box H/ACA RNA, sR-h45, was bioinformatically predicted before. We confirmed its presence as a double hairpin RNA inside the cell whose level goes down in the absence of Cbf5. We identified that sR-h45 is the guide RNA for sRNP-mediated Ys at the three above mentioned rRNA positions in H. volcanii. Each hairpin of this RNA can independently modify the substrate, both in vivo and in vitro. To characterize the structure of sR-h45, we have used a sR-h45 deleted strain where the function of sR-h45 was complemented with a plasmid-borne copy of the gene. By a combination of in vivo and in vitro mutagenic approaches, we determined specific nucleotides/structures of this RNA, involved in binding to the core proteins and also to the substrate RNA. We also identified that one hairpin of sR-h45 can modify two successive positions (1940 and 1942) in rRNA.
6

STRUCTURAL AND FUNCTIONAL STUDIES OF ARCHAEAL SMALL GUIDE RNAS AND THE ROLES OF HUMAN PSEUDOURIDINE SYNTHASES FOR Ψ55 FORMATION IN tRNAS

mukhopadhyay, shaoni 01 May 2020 (has links)
Over one hundred types of chemical modifications have been characterized in cellular RNAs. Pseudouridines (Ψ) and 2’-O-methylation of ribose sugars are the two most widespread modifications present in rRNAs, tRNAs and snRNAs. These modifications can be either guide-RNA mediated or RNA-independent (enzyme only). The RNAs that guide pseudouridylations are called box H/ACA RNAs and the ones that carry out 2’-O-methylations modifications are called box C/D RNAs. Previously, we identified that sR-h45 is the box H/ACA guide RNA responsible for Ψ1940, 1942 and 2605 formation in 23S rRNA of Haloferax volcanii. This RNA has two stem loops – SL1 and SL2. SL1 acts as the guide for Ψ2605 formation and SL2 is responsible for guiding Ψ1940 and Ψ1942. We found that SL2 sequentially guides Ψ1940 and Ψ1942 formation in the unpaired "UNUN" target. Ψ1942 is produced after and only if Ψ1940 is produced. The requirement for conserved ACA box was determined by using variants of these two stem loops. We found that the ACA motif is not required either in vivo or in vitro for the activity of the typical variants of both SL1 and SL2 but required for the activity of the atypical variants of these guides. Cbf5 is the pseudouridine synthase involved in this box H/ACA RNA guided process. Mutants of Methanocaldococcus jannaschii Cbf5 were used with both typical and atypical guide variants in vitro and certain residues were found to be important only for the atypical reactions.We have also studied sR-h41, which is a unique single guide box C/D guide responsible for methylation of G1934 position of 23S rRNA of Haloferax volcanii. We have done in vitro assembly reactions using mutants of sR-h41 assembled with its cognate proteins from Methanocaldococcus jannaschii to study the structural determinants needed to convert it to a dual guide RNA. The assembly pattern of the core proteins on the conserved box C/D and box C’/D motifs steer the dual guide nature of these archaeal box C/D guide RNAs.Another aim of this study was to determine the role of pseudouridine synthases (Pus enzymes) for Ψ55 formation in mammalian tRNAs. We find that three Pus enzymes – TruB1 (in the nucleus), TruB2 (in the mitochondria) and Pus10 (in the cytoplasm) are responsible for this modification depending on the specific sub-cellular location in the cell. These enzymes exhibit different structural requirement for Ψ55 formation that are located on the TΨC loop of tRNAs. A subset of tRNAs like tRNAs for Trp and Gln are protected from the action of TRUB1 in the nucleus by binding to the nuclear version of Pus10 that lacks Ψ55 activity. Ψ55 in this subset of tRNAs is produced by the cytoplasmic version of Pus10.While studying pseudouridylation functions of Pus10, we also found that Pus10 regulates G1/S cell cycle progression in PC3 cells. It does so by directly repressing another protein c-Rel, that is a positive regulator of Cyclin D1 protein. Cyclin D1 is known to play a central role in transition of cell from G1 to S phase during cell cycle progression. c-Rel also regulates the levels of PUS10 by an unknown mechanism.
7

Regulation of the yifK locus by multi-target small RNA GcvB in Salmonella / Régulation du gène yifK par le petit ARN multi-cible GcvB chez Salmonella

Yang, Qi 19 September 2013 (has links)
GcvB est un ARN bactérien conservé de 200 nucléotides, qui régule négativement l’expression de plusieurs gènes impliqués dans l’import et la biosynthèse des acides aminés. Bien que le rôle physiologique de GcvB ne soit pas complètement élucidé, il contribuerait vraisemblablement à équilibrer les ressources nutritionnelles en conditions de croissance rapide. GcvB inhibe la traduction des ARNm cibles en s’appariant avec des séquences à l’intérieur ou en amont du site de liaison du ribosome. Dans cette étude, la caractérisation d’un nouveau locus régulé par GcvB a permis de dévoiler des aspects singuliers du mode de fonctionnement de cet ARN régulateur. Nous avons découvert que GcvB réprime yifK - un gène très conservé, codant pour un transporteur d’acides aminés putatif - en ciblant un élément activateur de la traduction sur l’ARNm. Deux motifs ACA dans la séquence cible sont les déterminants principaux de la fonction activatrice. Le remplacement de l’un ou l’autre avec des triplets aléatoires, provoque une diminution de 10 fois du niveau d’expression de yifK, quelque soit l’allèle de GcvB (délétion ou changement de séquence permettant la reconnaissance de la cible mutante). Il apparait ainsi que l’efficacité de GcvB à réguler négativement sa cible serait liée a sa capacité d’antagoniser l’élément activateur. Lorsque l’activateur est éliminé, l’action de GcvB n’est plus un facteur limitant pour l’expression de yifK. Dans son ensemble, cette étude apporte une meilleure compréhension de la fonction de GcvB et révèle un nouvel aspect du processus d’initiation de la traduction. En plus du contrôle par GcvB, le locus yifK est régulé au niveau transcriptionnel par Lrp (leucine-responsive regulatory protein) et par HdfR (YifA) un régulateur transcriptionnel peu connu qui requerrait le produit du gène adjacent orienté de façon divergente, yifE, pour son expression ou activité. Enfin, la transcription initiée au niveau du promoteur yifK s’étend dans l’opéron d’ARNt argX-hisR-leuT-proM adjacent, donnant lieu à un transcrit primaire qui est à la fois un lARNm et un précurseur des ARNt. Cet ARN chimère est rapidement maturé par l’ARNase E. / GcvB is a conserved 200 nucleotide RNA that downregulates several genes involved in amino acid uptake or biosynthesis in bacteria. The physiological role of GcvB action is not entirely clear, but it is likely aimed at balancing of nutritional resources under fast growth conditions. GcvB inhibits translation of target messenger RNAs by pairing with sequences inside or upstream of ribosome binding sites. In the present study, characterization of a novel GcvB-regulated locus revealed some unique features in the mode of functioning of this regulatory RNA. We found that GcvB represses yifK - a highly conserved locus encoding a putative amino acid transporter - by targeting a translational enhancer element. Two ACA motifs within the target sequence are the main determinants of the enhancer activity. Replacing either of these motifs with random triplets caused up to a 10-fold decrease in yifK expression regardless of the GcvB allele (deleted or suitably modified to recognize the mutated target). It thus appears that GcvB effectiveness as a regulator results from countering the enhancer activity. When the enhancer is removed, GcvB action no longer constitutes a rate-limiting factor for yifK expression. Overall, this study is relevant not only to a better understanding of GcvB function but it also provides insight into an elusive aspect of the translation initiation process. Besides the GcvB control, the yifK locus is regulated at the transcriptional level by the leucine responsive regulator Lrp, and by HdfR (YifA) a poorly known transcriptional regulator, that appears to require the product of the adjacent, divergently oriented gene, yifE, for expression or activity. Transcription initiating at the yifK promoter extends into the adjacent argX-hisR-leuT-proM tRNA operon yielding an unusual primary transcript which both a messenger RNA and a tRNA precursor. This chimeric RNA si rapidly processed by RNAse E.
8

Étude du rôle du complexe SMN dans l’assemblage de RNP non codantes ubiquitaires : la SRP, les RNP C/D et H/ACA dont la télomérase, et étude du taux des facteurs d’assemblage de la télomérase dans les cellules cancéreuses / Study of the role of the SMN complex in the assembly of ubiquitous not coding RNPs : SRP, C/D and H/ACA box RNPs and telomerase, and study of the level of telomerase assembly factors in cancer cells

Dodré, Maxime 18 December 2014 (has links)
Les particules ribonucléoprotéiques (RNP) sont impliquées dans divers mécanismes cellulaires : les UsnRNP, la SRP, les RNP à boîtes C/D et H/ACA dans la modification des ARN et la maturation des ARN ribosomiques, et la télomérase dans le maintien des extrémités chromosomiques. L'assemblage de ces RNP est un processus complexe faisant intervenir de nombreux facteurs, dont le complexe SMN. Un déficit de l’une des protéines de ce complexe conduit à l’amyotrophie spinale. Il est essentiel à la survie cellulaire et est nécessaire à l’assemblage des UsnRNP et de la SRP. Il est suggèré que le complexe SMN joue un rôle dans la biogenèse des RNP à boîtes C/D et H/ACA. Nous avons montré des interactions in vitro et des associations in cellulo entre le complexe SMN et la protéine NUFIP (un facteur d’assemblage de ces RNP). Ces résultats suggèrent l’existence d’un lien fonctionnel entre le complexe SMN et NUFIP dans l'assemblage des RNP à boîtes C/D et H/ACA et de la snRNP U4. Des interactions in vitro entre le complexe SMN et la protéine NAF1 (un facteur d’assemblage des RNP à boîtes H/ACA) ont révélés, que le complexe SMN est capable de s’associer avec la RNP à boîtes H/ACA en formation. Si le complexe SMN intervient dans l’assemblage des RNP, on peut supposer que cet assemblage soit défectueux dans la SMA. Nous avons montré que certains ARN sont accumulés dans la moelle épinière et le cerveau de souris SMA. La télomérase est réactivée dans les cellules cancéreuses. En collaboration avec l’équipe de J-M Vignaud (CHU central, Nancy), nous avons montré une augmentation du taux des protéines cœur des RNP à boîtes H/ACA et de NUFIP dans les cellules tumorales / Ribonucleoprotein particles (RNPs) are involved in various cellular mechanisms in eukaryotic cells: UsnRNP, SRP, C/D and H/ACA box RNPs in RNA modifications and rRNA maturation and telomerase in the synthesis of the chromosome extremities. RNP assembly is a very complex process, which involves numerous factors. One of these factors is the SMN complex. Decreased level of one of its components leads to spinal muscular atrophy. It is essential for cell survival and necessary for UsnRNP and SRP assembly. It is suggested that the SMN complex plays a role in C/D and H/ACA RNP biogenesis. We showed in vitro interactions and in cellulo associations between the SMN complex and the protein NUFIP (an assembly factor of these RNP). These results suggest the existence of a functional link between the SMN complex and NUFIP in the assembly of the C/D and H/ACA box RNPs and the U4 snRNP. In vitro interactions between the SMN complex and the protein NAF1 (an assembly factor of the H/ACA boxes RNPs) revealed, that the SMN complex is capable of joining with the H/ACA boxes RNPs in formation. If the SMN complex intervenes in the RNPs assembly, we can suppose that this assembly is defective in the SMA. We showed that any ARN is accumulated in the spinal cord and the brain of SMA mouse. The telomerase is reactivated in cancer cells. In association with the team of J-M Vignaud (CHU central, Nancy), we showed an increase of H/ACA box RNP proteins and NUFIP in these cancer cells
9

Efeitos do exerc?cio f?sico aer?bio na modula??o autonomica da frequ?ncia card?aca de mulheres com sindrome dos ov?rios policisticos

S?, Joceline C?ssia Ferezini de 29 October 2013 (has links)
Made available in DSpace on 2014-12-17T14:13:51Z (GMT). No. of bitstreams: 1 JocelineCFS_TESE.pdf: 9953676 bytes, checksum: 9e87c154e4492433b05652a1e5ae5096 (MD5) Previous issue date: 2013-10-29 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / O objetivo deste estudo foi analisar o efeito do treinamento f?sico aer?bico (TFA) na modula??o auton?mica card?aca, avaliado pela variabilidade da frequ?ncia card?aca (VFC), em mulheres com s?ndrome dos ov?rios polic?sticos (SOP). Participaram do estudo 30 mulheres na faixa et?ria entre 18 e 34 anos, com diagn?stico de SOP de acordo com o Consenso de Rotterdam, e foram divididas em dois grupos: 1) grupo treinamento (GT; n=15) que conclu?ram programa de treinamento aer?bico durante 16 semanas, tr?s vezes por semana e 40 minutos por sess?o; e 2) grupo controle (GC; n=15) que n?o participaram do treinamento. A VFC foi analisada antes e ap?s o per?odo de estudo, sendo analisada pelos m?todos linear e n?o-linear. Para avaliar o efeito do treinamento sobre as vari?veis da an?lise da VFC foi ajustado um modelo de an?lise de covari?ncia multivariado (MANCOVA) tendo como covari?veis o IMC (?ndice de massa corporal), a Insulina e a Testosterona e como fator explicativo o grupo (tratamento, controle). As caracter?sticas cl?nicas quanto ao peso, circunfer?ncia de cintura, IMC, press?o arterial, frequ?ncia card?aca, VO2 m?x (consumo m?ximo de oxig?nio), insulina de jejum e testosterona, n?o apresentaram diferen?a estatisticamente significativa (p>0.05) entre os grupos pr?-interven??o. Tanto a FC (frequ?ncia card?aca) como a press?o arterial sist?lica de repouso, apresentaram diminui??o estatisticamente significativa no grupo treinado ap?s as 16 semanas (p=0.016; p=0.001 respectivamente). Observaram-se aumentos significativos no RMSSD ( raiz quadrada da somat?ria dos quadrados das diferen?as entre os intervalos R-R normais adjacentes) - (p < 0,0001) e no SDNN (desvio-padr?o da m?dia de todos os intervalos RR normais) - (p = 0,002). Na an?lise espectral no dom?nio da frequ?ncia foi encontrado aumento significativo no AF (alta frequ?ncia) em unidades absolutas (p < 0,0001), a vari?vel AFun (alta frequ?ncia em unidades normalizadas) tamb?m apresentou um aumento significativo (p < 0,001), enquanto que BFun (baixa frequ?ncia em unidades normalizadas) demonstrou diminui??o significativa (p < 0,001). Na an?lise das vari?veis pelo m?todo n?o-linear foram encontradas diferen?as significativas na ES (Entropia de Shannon), 0V% (porcentagem de padr?es sem varia??o) e 2VD% (porcentagem de padr?es com duas varia??es diferentes) (p<0,05), caracterizando uma melhora na modula??o auton?mica da frequ?ncia card?aca do grupo treinado. O TFA melhorou a VFC em repouso de mulheres com SOP, caracterizado pelo aumento na modula??o parassimp?tica e redu??o da modula??o simp?tica na frequ?ncia card?aca. Os resultados refor?am a import?ncia da abordagem interdisciplinar na avalia??o e tratamento de mulheres com SOP, com vistas ? redu??o de morbidade relacionada ao sistema cardiovascular
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Medidas de par?metros morfol?gicos e funcionais do Cora??o em brasileiros: um subestudo do primeiro registro multic?ntricos latino-americano em resson?ncia magn?tica cardi?ca

Macedo Filho, Robson de 06 May 2013 (has links)
Made available in DSpace on 2014-12-17T14:14:01Z (GMT). No. of bitstreams: 1 RobsonMF_DISSERT.pdf: 1631191 bytes, checksum: 260bb5fe4f1e2f487d506e21842e62a3 (MD5) Previous issue date: 2013-05-06 / Funda??o de Amparo a Pesquisa do Estado de S?o Paulo / There is no data about cardiac measurements em Brazilians obtained by CMR. This a muldisciplinary study with the objective of obtaining measurements of the left ventricle (LV) and right ventricle (RV) diastolic diameter (Dd), systolic diameter (Ds), diastolic volume (Dv), systolic volume (Sv), ejection fraction (EF) and myocardial mass in Brazilians. One hundred and seven (54 men and 53 women, mean age of 43.4 ? 13.1 years) asymptomatic individuals without heart disease were submitted to cardiac magnetic resonance (cMR) studies using steady state free precession technique. The means and standard deviations of the parameters of the LV and RV were respectively: LVDD = 4,8 ? 0,5 cm; LVSD = 3,0?0,6 cm; LVDV = 128,4?29,6 ml; LVSV = 45,2?16,6 ml; LVEF = 65,5?6,3%; LV mass = 95,2?30,8.1 g; RVDD = 3,9?1,3 cm; RVSD = 2,5?0,5 cm; RVDV = 126,5?30,7 ml; RVSV = 53.6?18,4 ml; RVEF = 58.3?8,0.0% and RV mass = 26,1?6,1 g. The masses and volumes were significantly higher in men, except for the LVSV. The RV EF was significantly higher in women. There was inverse correlation between RV systolic volume and with age, being more significant in men. This study describes for the first time benchmarks for cardiac measurements obtained by CMR among asymptomatic Brazilians individuals without heart disease and demonstrated differences according to sex and age / N?o h? dados nacionais sobre medidas card?acas obtidas por Resson?ncia Magn?tica Card?aca (RMc). Esse trabalho multidisciplinar teve como objetivo obter medidas do di?metro diast?lico (Dd), di?metro sist?lico (Ds), volume diast?lico final (VdF), volume sist?lico final (VsF), fra??o de eje??o (FE) e da massa mioc?rdica dos ventr?culos esquerdo (VE) e direito (VD) em brasileiros. Cento e sete (107) indiv?duos, 54 homens e 53 mulheres, com idade m?dia de 43,4 ? 13,1 anos, assintom?ticos e sem cardiopatias, foram submetidos ? RMc, utilizando t?cnica de precess?o livre em estado de equil?brio. As m?dias e os desvios padr?es dos par?metros do VE e VD foram respectivamente: Dd VE = 4,8 ? 0,5 cm; Ds VE = 3,0 ? 0,6 cm; VdF VE = 128,4 ? 29,6 ml; VsF VE = 45,2 ? 16,6 ml; FEVE = 65,5 ? 6,3%; massa do VE = 95,2 ? 30,8 g; Dd VD = 3,9 ? 1,3 cm; Ds VD = 2,5 ? 0,5cm; VdF VD = 126,5 ? 30,7 ml; VsF VD = 53,6 ? 18,4 ml; FEVD = 58,3 ? 8,0% e massa do VD = 26,1 ? 6,1 g. As massas e volumes foram significativamente maiores nos homens, exceto para o VsF do VE. A fra??o de eje??o do VD foi significativamente maior nas mulheres. Houve correla??o significativa e inversa do Vs do VD com o aumento da idade, sendo mais significativo nos homens. Esse estudo descreve, pela primeira vez, medidas card?acas obtidas pela RMc em brasileiros, as quais revelam diferen?as de acordo com o sexo e a idade

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