Estudio del rol del factor UBF en la expresión de poblaciones de rDNA variantes durante la adaptación estacional de Cyprinus carpio.

Tesis (Doctor en Biociencias Moleculares)RESUMEN: La biogénesis ribosomal es uno de los procesos cruciales a nivel celular. En la regulación de este proceso participan dos mecanismos principales: uno que involucra los factores de transcripción clásicos de la RNA polimerasa I (RNA PolI), y un segundo que consiste en el despliegue de mecanismos epigenéticos. Actualmente, existe conocimiento de que ambas vías se encontrarían íntimamente relacionadas. En este contexto el pez Cyprinus carpio (carpa), presenta características especiales en cuanto a la regulación de la biogénesis ribosomal. Previamente, se ha reportado que durante el ciclo estacional este organismo debe implementar un proceso de adaptación a nivel molecular para adecuar el proceso fundamental de síntesis de ribosomas. La carpa durante la estación invernal sufre una segregación de sus componentes nucleolares, acompañada de un reordenamiento de la cromatina nucleolar, lo cual finalmente se traduce en una disminución de la expresión de los genes ribosomales. Este fenotipo celular es revertido al llegar la estación veraniega, continuando un proceso cíclico genéticamente programado denominado aclimatización estacional. Estos antecedentes han permitido postular que este organismo es capaz de generar mecanismos moleculares de adaptación compensatorios frente a los cambios en su entorno. Hasta nuestro conocimiento, la carpa constituye el único organismo en donde se ha descrito y estudiado que el efecto de estímulos medioambientales es capaz de controlar la transcripción de los genes ribosomales a lo largo del ciclo estacional. Por esta razón, C. carpio es un extraordinario modelo de estudio tanto para el control de la biogénesis ribosomal, como para profundizar el conocimiento sobre el efecto los estímulos medioambientales en la reprogramación génica de un organismo. En este trabajo de tesis hemos centrado nuestro estudio en la proteína UBF (Upstream Binding Factor). Esta proteína ha sido caracterizada como un factor de transcripción de la RNA PolI, que interviene en la formación del complejo de pre-iniciación sobre el promotor de los genes ribosomales. Sin embargo, recientemente se ha descrito que este factor también interviene ayudando a mantener la transcripción ribosomal activa. Así, otros estudios han demostrado que la proteína UBF no sólo se une al promotor del cistrón ribosomal, sino que también interactúa con gran parte de la secuencia del cistron ribosomal. En este caso, UBF desempeñaría un rol fundamental en la expresión de las diferentes poblaciones de estos genes,..ABSTRACT: Ribosomal biogenesis is a critical process at a cellular level. Two main mechanisms participate in the regulation of this process: one involving typical transcription factors of RNA polymerase I (RNA Pol I) and a second consisting of a display of epigenetic mechanisms. Nowadays, studies have proved that both pathways are closely related. Cyprinus carpio (carp) has special features concerning ribosomal biogenesis regulation. It has been previously reported that during each seasonal cycle, this organism must go through an adaptation process at a molecular level in order to adjust the fundamental process of ribosomal synthesis. During winter time, the carp undergoes a segregation process of the nucleolar components along with a rearrangement of the nucleolar chromatin, which results in a decreased expression of ribosomal genes. This cellular phenotype is reverted in the summer season, thus creating a genetically programmed cyclical process known as seasonal acclimatization. This suggests that this organism could generate compensatory molecular adaptation mechanisms when its environment changes. To our knowledge, modulation of ribosomal genes at a transcriptional level in response to environmental changes has been described only in carp. For these reasons, C. carpio represents an excellent model to study the mechanisms controlling ribosomal biogenesis, allowing us at the same time to deepen our knowledge about the effects of environmental stimuli over this and other processes. This thesis is focused on the protein UBF (Upstream Binding Factor), one of the several factors involved in ribosomal regulation. This protein has been characterized as a transcription factor for RNA Pol I, directly intervening in the formation of the pre-initiation complex in the ribosomal gene. However, it has been recently reported that this factor also acts as a maintainer of ribosomal transcription. Other studies have shown that UBF not only binds to the promoter of the ribosomal cistron but also interacts with a large part of the ribosomal gene sequence. If that is the case, UBF might have a significant role in the expression of ribosomal genes, keeping them in a structurally active state. Overall, these allow us to suggest UBF as a central factor in the regulation of ribosomal gene transcription, and our hypothesis is that UBF differentially controls the expression of rRNA during seasonal acclimation on C. Carpio by controlling the activity of a variant forms of rDNA (v-rDNA)..

Using torsion to manipulate spin currents

We address the problem of quantum particles moving on a manifold characterised by the presence of torsion along a preferential axis. In fact, such a torsion may be taylored by the presence of a single screw dislocation, whose Burgers vector measures the torsion amplitude. The problem, first treated in the relativistic limit describing fermions that couple minimally to torsion, is then analysed in the Pauli limit We show that torsion induces a geometric potential and also that it couples generically to the phase of the wave function, giving rise to the possibility of using torsion to manipulate spin currents in the case of spinor wave functions. These results emerge as an alternative strategy for using screw dislocations in the design of spintronic-based devices

O gene da adiponectina e o risco cardiovascular em pacientes com diabetes tipo 2: uma revisão das evidiencias

Diabetic patients have a 3-fold higher risk of developing atherosclerosis and its clinical complications as compared to non-diabetic individuals. Part of the cardiovascular risk associated with diabetes is probably due to genetic determinants influencing both glucose homeostasis and the development of atherosclerosis. However, type 2 diabetes frequently coexists with other cardiovascular risk factors like arterial hypertension, central obesity and dyslipidemia. Genetic variability affecting many areas such as lipid and energy metabolisms, hypertension and haemodynamic mechanisms, blood clotting homeostasis, inflammation, and matrix turnover in the vascular wall will have an impact on the development of macrovascular complications in diabetic patients. Adiponectin is abundantly secreted by adipocytes. It plays important roles in lipid and glucose metabolisms and has direct anti-inflammatory and anti-atherogenic effects. In this review, we summarize recent data from the literature suggesting an implication of allelic variations of the adiponectin gene (ADIPOQ) in the genetic determinants of cardiovascular disease in diabetic subjects.Os pacientes com diabetes apresentam risco três vezes maior de desenvolverem aterosclerose e suas complicações quando comparados a indivíduos sem hiperglicemia. Parte desse risco associado ao diabetes é provavelmente relacionado a determinantes genéticos que influenciam tanto a homeostase glicídica quanto o desenvolvimento da aterosclerose. Entretanto, o diabetes tipo 2 freqüentemente coexiste com outros fatores de risco cardiovascular, tais como hipertensão arterial, obesidade central e dislipidemia. A variabilidade genética interfere em várias áreas tais como o metabolismo lipídico, o metabolismo energético, hipertensão, mecanismos hemodinâmicos, mecanismos de coagulação, inflamação e na formação da matriz na parede vascular, que podem estar envolvidos nas complicações macrovasculares dos pacientes com diabetes. A adiponectina é secretada com abundância pelos adipócitos. Apresenta importante papel no metabolismo lipídico e glicídico, tendo ação direta tanto antiinflamatória quanto anti-aterogênica. Na atual revisão, nós resumimos os dados recentes da literatura que sugerem uma implicação de variantes alélicas do gene da adiponectina (ADIPOQ) que podem estar envolvidos na determinação genética da doença cardiovascular em indivíduos com diabetes.São Paulo University Laboratory of Cellular and Molecular EndocrinologyFederal University of São Paulo Laboratory of Molecular EndocrinologyFleury InstituteINSERMUniversité Paris 7UNIFESP, Laboratory of Molecular EndocrinologySciEL

Decreased insulin secretion and increased risk of type 2 diabetes associated with allelic variations of the WFS1 gene: the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study

We investigated associations of allelic variations in the WFS1 gene with insulin secretion and risk of type 2 diabetes in a general population prospective study.We studied 5,110 unrelated French men and women who participated in the prospective Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study. Additional cross-sectional analyses were performed on 4,472 French individuals with type 2 diabetes and 3,065 controls. Three single nucleotide polymorphisms (SNPs) were genotyped: rs10010131, rs1801213/rs7672995 and rs734312.We observed statistically significant associations between the major alleles of the three variants and prevalent type 2 diabetes in the DESIR cohort at baseline. Cox analyses showed an association between the G-allele of rs10010131 and incident type 2 diabetes (HR 1.34, 95% CI 1.08-1.70, p = 0.007). Similar results were observed for the G-allele of rs1801213 and the A-allele of rs734312. the GGA haplotype was associated with an increased risk of diabetes as compared with the ACG haplotype (HR 1.26, 95% CI 1.04-1.42, p = 0.02). We also observed statistically significant associations of the three SNPs with plasma glucose, HbA(1c) levels and insulin secretion at baseline and throughout the study in individuals with type 2 diabetes or at risk of developing diabetes. However, no association was observed in those who remained normoglycaemic at the end of the follow-up. Associations between the three variants and type 2 diabetes were replicated in cross-sectional studies of type 2 diabetic patients in comparison with a non-diabetic control group.The most frequent haplotype at the haplotype block containing the WFS1 gene modulated insulin secretion and was associated with an increased risk of type 2 diabetes.Societe Francophone du Diabete (SFD - Alfediam)Association Diabete Risque Vasculaire (ADRV), FranceCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)INSERMCNAMTSLillyNovartis PharmaSanofi-AventisINSERM (Reseaux en Sante Publique, Interactions entre les determinants de la sante)Association Diabete Risque VasculaireFederation Francaise de CardiologieLa Fondation de FranceALFEDIAMONIVINSArdix MedicalBayer DiagnosticsBecton DickinsonCardionicsMerck SanteNovo NordiskPierre FabreRocheTopconUniv Paris 07, INSERM, Res Unit 695, F-75018 Paris, FranceFed Univ Hlth Sci Porto Alegre, Postgradut Program Hlth Sci, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, BrazilAssistance Publ Hop Paris Cochin Hosp, Dept Immunol & Diabetol, Paris, FranceUniv Paris 05, UFR Med, Paris, FranceUniv Paris 07, UFR Med, Paris, FranceAssistance Publ Hop Paris Bichat Hosp, Dept Endocrinol Diabetol & Nutr, Paris, FranceInst Inter Reg Sante IRSA, La Riche, FranceINSERM, U1018, CESP, Ctr Res Epidemiol & Populat Hlth, Villejuif, FranceUniv Paris 11, UMRS 1018, Villejuif, FranceUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, BrazilCAPES: 1798-09-0Web of Scienc

Introduction to topological defects: from liquid crystals to particle physics

Liquid crystals are assemblies of rod-like molecules which self-organize to form mesophases, in-between ordinary liquids and anisotropic crystals. At each point, the molecules collectively orient themselves along a privileged direction, which locally defines an orientational order. Sometimes, this order is broken and singularities appear in the form of topological defects. This tutorial article is dedicated to the geometry, topology and physics of these defects. We introduce the main models used to describe the nematic phase and discuss the isotropic-nematic phase transition. Then, we present the different families of defects in nematics and examine some of their physical outcomes. Finally, we show that topological defects are universal patterns of nature, appearing not only in soft matter, but also in biology, cosmology, geology and even particle physics.Comment: 40 pages, 9 figures, review pape

The common-866G > A variant in the promoter of UCP2 is associated with decreased risk of coronary artery disease in type 2 diabetic men

OBJECTIVE-Uncoupling protein 2 (UCP2) is a physiological downregulator of reactive oxygen species generation and plays an antiatherogenic role in the vascular wall. A common variant in the UCP2 promoter (-866G>A) modulates mRNA expression, with increased expression associated with the A allele. We investigated association of this variant with coronary artery disease (CAD) in two cohorts of type 2 diabetic subjects.RESEARCH DESIGN and METHODS-We studied 3,122 subjects from the 6-year prospective Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Cardiovascular Events, and Ramipril (DIABHYCAR) Study (14.9% of CAD incidence at follow-up). An independent, hospital-based cohort of 335 men, 52% of whom had CAD, was also studied.RESULTS-We observed an inverse association of the A allele with incident cases of CAD in a dominant model (hazard risk 0.88 [95% CI 0.80-0.96]; P = 0.006). Similar results were observed for baseline cases of CAD. Stratification by sex confirmed an allelic association with CAD in men, whereas no association was observed in women. All CAD phenotypes considered-myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), and sudden death-contributed significantly to the association. Results were replicated in a cross-sectional study of an independent cohort (odds ratio 0.47 [95% CI 0.25-0.89]; P = 0.02 for a recessive model).CONCLUSIONS-The A allele of the -866G>A variant of UCP2 was associated with reduced risk of CAD in men with type 2 diabetes in a 6-year prospective study. Decreased risk of myocardial infarction, angina pectoris, CABG, and sudden death contributed individually and significantly to the reduction of CAD risk. This association was independent of other common CAD risk factors.INSERM, Fac Med Xavier Bichat, U695, F-75018 Paris, FranceCochin Hosp, AP HP, Dept Immunol & Diabetol, Paris, FranceUniv São Paulo, Lab Cellular & Mol Endocrinol, São Paulo, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, BrazilFed Fac Fdn Med Sci Porto Alegre, Post Grad Program Med Sci, Porto Alegre, RS, BrazilHop La Pitie Salpetriere, Dept Cardiol, AP HP, Paris, FranceUniv Paris 07, Paris, FranceUniv Paris 05, Paris, FranceUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, BrazilWeb of Scienc