310 research outputs found
A quantum mechanical study of the phase stability and phase transition mechanisms in CaCO3 at finite temperature and pressure
First-principles calculations have been performed to explore
the temperature-pressure phase diagram of calcium carbonate (CaCO3) in a range of temperatures and pressures up to 1000 K and 10 GPa respectively. The calcite I - calcite II and calcite I - aragonite phase boundaries have been obtained. Imaginary phonon modes in the aragonite phase suggest pathways to three distinct alternative phases that involve symmetry breaking and distortion of the unit cell. The variation of the Gibbs free energy with pressure and temperature has been computed in the quasi-harmonic approximation. Several approaches have been discussed in this thesis for the most accurate determination of the temperature - pressure phase boundary. A method for determining the calcite I - calcite II second order phase boundary has been described in this work. Hybrid exchange and GGA density functional theory in the all-electron linear combination of atomic orbitals approximation have been exploited, as well as the effect of the inclusion of van der Waals dispersion corrections. The resultant theoretical phase diagram is compared to the available measurements. The detailed theoretical understanding of the phase transitions mechanisms developed in this thesis sets the basis for a future exploration of the thermodynamic stability phase of CaCO3. In this respect, the methodology described in this work could be used to predict the temperature - pressure phase boundaries of the rest of the polymorphs of this complex system, e.g. phase transitions occurring in calcite III, IIIb, IV, V and VI.Open Acces
Drosophila melanogaster dHCF Interacts with both PcG and TrxG Epigenetic Regulators
Repression and activation of gene transcription involves multiprotein complexes that modify chromatin structure. The integration of these complexes at regulatory sites can be assisted by co-factors that link them to DNA-bound transcriptional regulators. In humans, one such co-factor is the herpes simplex virus host-cell factor 1 (HCF-1), which is implicated in both activation and repression of transcription. We show here that disruption of the gene encoding the Drosophila melanogaster homolog of HCF-1, dHCF, leads to a pleiotropic phenotype involving lethality, sterility, small size, apoptosis, and morphological defects. In Drosophila, repressed and activated transcriptional states of cell fate-determining genes are maintained throughout development by Polycomb Group (PcG) and Trithorax Group (TrxG) genes, respectively. dHCF mutant flies display morphological phenotypes typical of TrxG mutants and dHCF interacts genetically with both PcG and TrxG genes. Thus, dHCF inactivation enhances the mutant phenotypes of the Pc PcG as well as brm and mor TrxG genes, suggesting that dHCF possesses Enhancer of TrxG and PcG (ETP) properties. Additionally, dHCF interacts with the previously established ETP gene skd. These pleiotropic phenotypes are consistent with broad roles for dHCF in both activation and repression of transcription during fly development
Dimorfismo sexual en un modelo de síndrome metabólico
The Metabolic Syndrome (MetS) is a group of disorders constituted by obesity of central
distribution, dyslipidemia, increase in blood pressure, hyperglycemia and insulin resistance.
Since lifestyle and genes are key in its development, in order to avoid MetS it is
recommended to combine a healthy lifestyle through a correct diet and aerobic exercise. The
serum and glucocorticoid-inducible kinase 1 (SGK1) would be involved in MetS
development. This kinase expression is regulated by hormones such as gluco- and mineralocorticoids and, at the transcriptional level, by osmotic and glucose changes. Previous data
published by my supervisors have shown as SGK1 overexpression in a model of laboratory
mice (B6.Tg.sgk1) is able to reproduce MetS. As there are differences in age and prevalence
between sexes in humans, it suggests that sexual hormones may play an important role in
MetS causes and/or development, the aims of this project are A) to review the state of the art
something to do with the implications of sexual hormones in MetS, B) to elaborate an
experimental design in order to research if sexual hormones are able to modify some wellknown parameters related to MetS. To this purpose, we propose to study in two strains of
adult laboratory mice (Wild type, WT, and transgenic one overactivated for SGK1,
B6.Tg.sgk1) which will be grouped by sexes and fed under a high and low fat diet,
respectively, and treated with three different dosage of EMD63863 (inhibitor of SGK1
activity). In order to expanding the level of knowledges on sexual hormones and MetS, we
propose a similar pattern design using human as experimental subjects
A genome-wide computational approach to define microRNA-Polycomb/ trithorax gene regulatory circuits in drosophila
Characterization of gene regulatory networks is fundamental to understanding homeostatic development. This process can be simplified by analyzing relatively simple genomes such as the genome of Drosophila melanogaster. In this work we have developed a computational framework in Drosophila to explore for the presence of gene regulatory circuits between two large groups of transcriptional regulators: the epigenetic group of the Polycomb/ trithorax (PcG/trxG) proteins and the microRNAs (miRNAs). We have searched genome-wide for miRNA targets in PcG/trxG transcripts as well as for Polycomb Response Elements (PREs) in miRNA genes. Our results show that 10% of the analyzed miRNAs could be controlling PcG/trxG gene expression, while 40% of those miRNAs are putatively controlled by the selected set of PcG/trxG proteins. The integration of these analyses has resulted in the predicted existence of 3 classes of miRNA-PcG/trxG crosstalk interactions that define potential regulatory circuits.
In the first class, miRNA-PcG circuits are defined by miRNAs that reciprocally crosstalk with PcG. In the second, miRNA-trxG circuits are defined by miRNAs that reciprocally crosstalk with trxG. In the third class, miRNA-PcG/ trxG shared circuits are defined by miRNAs that crosstalk with both PcG and trxG regulators. These putative regulatory circuits may uncover a novel mechanism in Drosophila for the control of PcG/trxG and miRNAs levels of expression. The computational framework developed here for Drosophila melanogaster can serve as a model case for similar analyses in other species. Moreover, our work provides, for the first time, a new and useful resource for the Drosophila community to consult prior to experimental studies investigating the epigenetic regulatory networks of miRNA-PcG/trxG mediated gene expressionWe thank Dr. Peter Freddolino (University of Michigan Medical School, USA) for kindly providing us with the Polycomb Response
Element genome-wide predictor (Khabiri and Freddolino, 2019) and Keith Harshman for carefully reading the manuscript. This work was supported by PID2020-114533 GB-C21 grant from Spanish Agencia Estatal de Investigacion/Ministerio de Ciencia e Innovaci on and by institutional grants from Fundacion Areces and Banco Santande
Polycomb Controls Gliogenesis by Regulating the Transient Expression of the Gcm/Glide Fate Determinant
The Gcm/Glide transcription factor is transiently expressed and required in the Drosophila nervous system. Threshold Gcm/Glide levels control the glial versus neuronal fate choice, and its perdurance triggers excessive gliogenesis, showing that its tight and dynamic regulation ensures the proper balance between neurons and glia. Here, we present a genetic screen for potential gcm/glide interactors and identify genes encoding chromatin factors of the Trithorax and of the Polycomb groups. These proteins maintain the heritable epigenetic state, among others, of HOX genes throughout development, but their regulatory role on transiently expressed genes remains elusive. Here we show that Polycomb negatively affects Gcm/Glide autoregulation, a positive feedback loop that allows timely accumulation of Gcm/Glide threshold levels. Such temporal fine-tuning of gene expression tightly controls gliogenesis. This work performed at the levels of individual cells reveals an undescribed mode of Polycomb action in the modulation of transiently expressed fate determinants and hence in the acquisition of specific cell identity in the nervous system. © 2012 Popkova et al.Fondation pour la Recherche Médicale and by Centre Européen de Recherche en Biologie et en Médecine; Association pour la Recherche sur le Cancer; Institut National de la Santé et de la Recherche Médicale; Centre National de la Recherche Scientifique; Université de Strasbourg; Hôpital de Strasbourg; Institut National du Cancer; the Agence Nationale de la Recherche; Alma Mater Studiorum; Università di Bologna; European Research Council (ERC-2008-AdG No 232947); Institut National de la Santé et de la Recherche Médicale; Centre National de la Recherche Scientifique; European Network of Excellence EpiGeneSys; Fundacion Mutua Madrileña (FMM-2006) and Ministerio de Ciencia y Tecnología (BFU-2008-5404)Peer Reviewe
Modificaciones de la amplitud articular de tobillo durante la marcha en niños afectos de PCI y pie equino tratados con TBA
El objetivo de este estudio fue comprobar el efecto de la TBA (BOTOXâ) en la amplitud articular
del tobillo durante la marcha en pacientes afectos de PCI. La muestra estuvo formada por 9 niños
con una media de 6 años de edad distribuyéndose en 4 grupos de estudio: control, hemipléjico,
dipléjico I y dipléjico II. Las variables cuantificadas fueron la máxima flexión dorsal y plantar
realizadas durante la marcha (calzados y descalzos) así como los porcentajes del CM en el que se
alcanzaron estos máximos. La técnica instrumental utilizada fue un sistema de fotogrametría vídeo
3D con el software Kinescan-IBV. Interrelacionando las cuatro variables sometidas a estudio, los
resultados obtenidos demostraron que cada grupo evolucionó de forma distinta. Mientras que el
grupo hemipléjico alcanzó los mejores resultados entre los 3 meses y 5 meses dependiendo de la
condición, el grupo dipléjico I lo consiguió a los 5 meses y 3 semanas el dipléjico II a los 9 meses y
3 semanas. La TBA permitió una mayor movilidad en la articulación del tobillo, sin embargo para
que también mejorara la marcha fue necesario que transcurriera un cierto tiempo para reeducarla,
necesitando un incremento de este periodo y del número de dosis de TBA cuanto mayor es la
alteración de la marcha.Peer Reviewe
Uncoupling of Genomic and Epigenetic Signals in the Maintenance and Inheritance of Heterochromatin Domains in Fission Yeast
Many essential aspects of genome function, including gene expression and chromosome segregation, are mediated throughout development and differentiation by changes in the chromatin state. Along with genomic signals encoded in the DNA, epigenetic processes regulate heritable gene expression patterns. Genomic signals such as enhancers, silencers, and repetitive DNA, while required for the establishment of alternative chromatin states, have an unclear role in epigenetic processes that underlie the persistence of chromatin states throughout development. Here, we demonstrate in fission yeast that the maintenance and inheritance of ectopic heterochromatin domains are independent of the genomic sequences necessary for their de novo establishment. We find that both structural heterochromatin and gene silencing can be stably maintained over an ∼10-kb domain for up to hundreds of cell divisions in the absence of genomic sequences required for heterochromatin establishment, demonstrating the long-term persistence and stability of this chromatin state. The de novo heterochromatin, despite the absence of nucleation sequences, is also stably inherited through meiosis. Together, these studies provide evidence for chromatin-dependent, epigenetic control of gene silencing that is heritable, stable, and self-sustaining, even in the absence of the originating genomic signals
Unipolar distributions of junctional Myosin II identify cell stripe boundaries that drive cell intercalation throughout Drosophila axis extension.
Convergence and extension movements elongate tissues during development. Drosophila germ-band extension (GBE) is one example, which requires active cell rearrangements driven by Myosin II planar polarisation. A combinatorial code of Toll receptors downstream of pair-rule genes contributes to this polarization via local cell-cell interactions. We developed novel computational methods to analyse the spatiotemporal dynamics of Myosin II. We show that initial Myosin II bipolar cell polarization gives way to unipolar enrichment at parasegmental boundaries and two further boundaries within each parasegment, concomitant with a doubling of cell number as the tissue elongates. These boundaries are the primary sites of cell intercalation, behaving as mechanical barriers and providing a mechanism for how cells remain ordered during GBE. Enrichment at parasegment boundaries during GBE is independent of Wingless signaling, suggesting pair-rule gene control. We propose an updated cell-cell interaction model for Myosin II polarization that we tested in a vertex-based simulation
To be or not to be: the importance of attendance in integrated physiology teaching using non-traditional approaches
<p>Abstract</p> <p>Background</p> <p>There is increasing use of non-traditional methods like problem-based learning, team-working and several other active-learning techniques in Physiology teaching. While several studies have investigated the impact of class attendance on the academic performance in traditional teaching, there is limited information regarding whether the new modalities are especially sensible to this factor.</p> <p>Methods</p> <p>Here, we performed a comparative study between a control group receiving information through traditional methods and an experimental group submitted to new methodologies in Physiology teaching.</p> <p>Results</p> <p>We found that while mean examination scores were similar in the control and the experimental groups, a different picture emerge when data are organized according to four categorical attendance levels. In the experimental group, scores were not different between the 1st and the 2nd exams (P = 0.429) nor between the 2nd and the 3<sup>rd </sup>exams (P = 0.225) for students that never or poorly attend classes, in contrast to the control group (P < 0.001). A score difference between attending students versus the absentees was maximal in the experimental versus the control group all along the different exams and in the final score.</p> <p>Conclusion</p> <p>We suggest that class attendance is critical for learning using non-traditional methods.</p
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