Causes and Consequences of Genome Expansion in Fungi

Fungi display a large diversity in genome size and complexity, variation that is often considered to be adaptive. But because nonadaptive processes can also have important consequences on the features of genomes, we investigated the relationship of genetic drift and genome size in the phylum Ascomycota using multiple indicators of genetic drift. We detected a complex relationship between genetic drift and genome size in fungi: genetic drift is associated with genome expansion on broad evolutionary timescales, as hypothesized for other eukaryotes; but within subphyla over smaller timescales, the opposite trend is observed. Moreover, fungi and bacteria display similar patterns of genome degradation that are associated with initial effects of genetic drift. We conclude that changes in genome size within Ascomycota have occurred using two different routes: large-scale genome expansions are catalyzed by increasing drift as predicted by the mutation-hazard model of genome evolution and small-scale modifications in genome size are independent of drift

Estado nutricional vinculado a ingesta alimentaria y actividad física que realizan estudiantes de séptimo grado de tres colegios privados. Managua-Nicaragua. Abril-Agosto 2015.

Estudio descriptivo de corte transversal en 150 estudiantes de séptimo grado de los colegios: Mi Redentor, Bautista y Jesús Divino Obrero del departamento de Managua. Se concluye que más de la mitad de estudiantes, presentaron estado nutricional normal. Coexiste malnutrición por déficit, y por exceso, asociado al riesgo cardiovascular y antecedentes patológicos familiares de hipertensión y diabetes. El desayuno es la comida que se saltaron con mayor frecuencia. El patrón alimentario lo conforman trece alimentos. La práctica de actividades físicas que realizan: caminar, correr, montar en bicicleta, jugar futbol, voleibol y baloncesto. En la clase de educación física los alumnos están siempre y algunas veces activos

A Mathematical Methodology for Determining the Temporal Order of Pathway Alterations Arising during Gliomagenesis

Human cancer is caused by the accumulation of genetic alterations in cells. Of special importance are changes that occur early during malignant transformation because they may result in oncogene addiction and thus represent promising targets for therapeutic intervention. We have previously described a computational approach, called Retracing the Evolutionary Steps in Cancer (RESIC), to determine the temporal sequence of genetic alterations during tumorigenesis from cross-sectional genomic data of tumors at their fully transformed stage. Since alterations within a set of genes belonging to a particular signaling pathway may have similar or equivalent effects, we applied a pathway-based systems biology approach to the RESIC methodology. This method was used to determine whether alterations of specific pathways develop early or late during malignant transformation. When applied to primary glioblastoma (GBM) copy number data from The Cancer Genome Atlas (TCGA) project, RESIC identified a temporal order of pathway alterations consistent with the order of events in secondary GBMs. We then further subdivided the samples into the four main GBM subtypes and determined the relative contributions of each subtype to the overall results: we found that the overall ordering applied for the proneural subtype but differed for mesenchymal samples. The temporal sequence of events could not be identified for neural and classical subtypes, possibly due to a limited number of samples. Moreover, for samples of the proneural subtype, we detected two distinct temporal sequences of events: (i) RAS pathway activation was followed by TP53 inactivation and finally PI3K2 activation, and (ii) RAS activation preceded only AKT activation. This extension of the RESIC methodology provides an evolutionary mathematical approach to identify the temporal sequence of pathway changes driving tumorigenesis and may be useful in guiding the understanding of signaling rearrangements in cancer development

Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms.

Substantial advances have been made recently in the pathobiology of pituitary tumors. Similar to many other endocrine tumors, over the last few years we have recognized the role of germline and somatic mutations in a number of syndromic or nonsyndromic conditions with pituitary tumor predisposition. These include the identification of novel germline variants in patients with familial or simplex pituitary tumors and establishment of novel somatic variants identified through next generation sequencing. Advanced techniques have allowed the exploration of epigenetic mechanisms mediated through DNA methylation, histone modifications and noncoding RNAs, such as microRNA, long noncoding RNAs and circular RNAs. These mechanisms can influence tumor formation, growth, and invasion. While genetic and epigenetic mechanisms often disrupt similar pathways, such as cell cycle regulation, in pituitary tumors there is little overlap between genes altered by germline, somatic, and epigenetic mechanisms. The interplay between these complex mechanisms driving tumorigenesis are best studied in the emerging multiomics studies. Here, we summarize insights from the recent developments in the regulation of pituitary tumorigenesis

G-quadruplex structures within the 3' UTR of LINE-1 elements stimulate retrotransposition

Long interspersed nuclear elements (LINEs) are ubiquitous transposable elements in higher eukaryotes that have a significant role in shaping genomes, owing to their abundance. Here we report that guanine-rich sequences in the 3' untranslated regions (UTRs) of hominoid-specific LINE-1 elements are coupled with retrotransposon speciation and contribute to retrotransposition through the formation of G-quadruplex (G4) structures. We demonstrate that stabilization of the G4 motif of a human-specific LINE-1 element by small-molecule ligands stimulates retrotransposition.S.B. is a Wellcome Trust Senior Investigator (grant 099232/z/12/z). The Balasubramanian group is supported by European Research Council Advanced Grant 339778, and receives core (C14303/A17197) and program (C9681/A18618) funding from Cancer Research UK

Automated Privacy Verification of Voting Systems.

Voting systems aim to provide trustworthiness in elections; however, they have always been a target of malicious behaviours due to difficulties in designing such complex systems and the enormous value of controlling the election results, causing unfair election outcome, loss of personal privacy and trust in democracy. This thesis aims to shed light on how voting systems, in particular, paper-based ones can be evaluated so as to provide a better level of confidence in their trustworthiness. This thesis advances the evaluation of the paper-based voting systems using formal methods with automated analysis. In analysis of security protocols, the formal definitions of protocol requirements need to be constructed precisely. To this end, a formal framework regarding the anonymity requirement has been given and demonstrated to be appropriate for the analysis of voting systems. Similarly, it has been demonstrated that the assumptions under which voting systems are secure should be well-defined for a rigorous security analysis with the automated analysis of the ThreeBallot voting system. Moreover, a novel approach has been proposed to analyse cryptographic voting systems under a passive attacker model using the Pret a Voter voting system as case study. Finally, an active powerful attacker has been adapted into the analysis of voting systems, and an automated formal analysis of vVote voting system has been conducted, which is under development for use in Victorian Electoral Commission (VEC) elections, Australia in 2014. With the analyses of voting systems performed in this thesis, the formal approach developed here has been demonstrated to be successful in the automated analysis of such complex systems using the process algebra, Communicating Sequential Processes (CSP), and the model checker, Failures-Divergence Refinement (FDR)

Automated Privacy Verification of Voting Systems.

Voting systems aim to provide trustworthiness in elections; however, they have always been a target of malicious behaviours due to difficulties in designing such complex systems and the enormous value of controlling the election results, causing unfair election outcome, loss of personal privacy and trust in democracy. This thesis aims to shed light on how voting systems, in particular, paper-based ones can be evaluated so as to provide a better level of confidence in their trustworthiness. This thesis advances the evaluation of the paper-based voting systems using formal methods with automated analysis. In analysis of security protocols, the formal definitions of protocol requirements need to be constructed precisely. To this end, a formal framework regarding the anonymity requirement has been given and demonstrated to be appropriate for the analysis of voting systems. Similarly, it has been demonstrated that the assumptions under which voting systems are secure should be well-defined for a rigorous security analysis with the automated analysis of the ThreeBallot voting system. Moreover, a novel approach has been proposed to analyse cryptographic voting systems under a passive attacker model using the Pret a Voter voting system as case study. Finally, an active powerful attacker has been adapted into the analysis of voting systems, and an automated formal analysis of vVote voting system has been conducted, which is under development for use in Victorian Electoral Commission (VEC) elections, Australia in 2014. With the analyses of voting systems performed in this thesis, the formal approach developed here has been demonstrated to be successful in the automated analysis of such complex systems using the process algebra, Communicating Sequential Processes (CSP), and the model checker, Failures-Divergence Refinement (FDR)