Transcription as a Threat to Genome Integrity

Genomes undergo different types of sporadic alterations, including DNA damage, point mutations, and genome rearrangements, that constitute the basis for evolution. However, these changes may occur at high levels as a result of cell pathology and trigger genome instability, a hallmark of cancer and a number of genetic diseases. In the last two decades, evidence has accumulated that transcription constitutes an important natural source of DNA metabolic errors that can compromise the integrity of the genome. Transcription can create the conditions for high levels of mutations and recombination by its ability to open the DNA structure and remodel chromatin, making it more accessible to DNA insulting agents, and by its ability to become a barrier to DNA replication. Here we review the molecular basis of such events from a mechanistic perspective with particular emphasis on the role of transcription as a genome instability determinant

Transcription-mediated replication hindrance: a major driver of genome instability

Genome replication involves dealing with obstacles that can result from DNA damage but also from chromatin alterations, topological stress, tightly bound proteins or non-B DNA structures such as R loops. Experimental evidence reveals that an engaged transcription machinery at the DNA can either enhance such obstacles or be an obstacle itself. Thus, transcription can become a potentially hazardous process promoting localized replication fork hindrance and stress, which would ultimately cause genome instability, a hallmark of cancer cells. Understanding the causes behind transcription–replication conflicts as well as how the cell resolves them to sustain genome integrity is the aim of this review

Overview. Preterm labour: mechanisms and management

Preterm birth remains a major cause of perinatal mortality and long term handicap in surviving infants. This is one of the most important clinical problems in Europe and across the world. While some preterm births are iatrogenic, associated with severe complications of pregnancy (e.g. hypertensive disorders, antepartum haemorrhage, infection), or the result of multiple pregnancies following assisted reproduction, a high proportion of preterm births occur following spontaneous preterm labour of unknown cause. Early intervention in this group of women would have a significant impact on neonatal mortality and morbidity figures. However, the endocrine changes preceding parturition in women remain elusive and this makes it difficult to predict spontaneous labour at term, let alone preterm labour. Moreover our understanding of myometrial physiology remains rudimentary, limiting our options to devise improved pharmacological strategies to control uterine contractility when this is indicated. There is a need for concerted European and international research efforts to improve our knowledge of the mechanism of labour in women, to identify diagnostic markers to predict preterm labour and to develop uterine selective drugs to inhibit uterine contractions in a safe and efficient manner. This aim will be achieved by multidisciplinary research efforts from academics and industry, using traditional laboratory and clinical research methods, as well as novel technologies

Impact assessment of a new parking pricing écheme in Madrid city centre.

Ponencia en Congres

Structures and Stabilities of Doubly-charged (MgO)nMg2+ (n=1-29) Cluster Ions

Ab initio perturbed ion plus polarization calculations are reported for doubly-charged nonstoichiometric (MgO)nMg2+ (n=1-29) cluster ions. We consider a large number of isomers with full relaxations of the geometries, and add the correlation correction to the Hartree-Fock energies for all cluster sizes. The polarization contribution is included at a semiempirical level also for all cluster sizes. Comparison is made with theoretical results for neutral (MgO)n clusters and singly-charged alkali-halide cluster ions. Our method is also compared to phenomenological pair potential models in order to asses their reliability for calculations on small ionic systems. The large coordination-dependent polarizabilities of oxide anions favor the formation of surface sites, and thus bulklike structures begin to dominate only after n=24. The relative stabilities of the cluster ions against evaporation of a MgO molecule show variations that are in excellent agreement with the experimental abundance spectra.Comment: Final version accepted in Journal of Chemical Physics; 8 pages plus 8 figures (6 GIFs and 2 PSs). The main difference with respect to the original submission is the inclusion of coordination-dependent polarizabilities for oxide anions. That results in substantial changes in the result

Biomechanical analysis of a cranial Patient Specific Implant on the interface with the bone using the Finite Element Method

- New advance technologies based on reverse engineering , design and additive manufacturing, have expanded design capabilities for biomedical applications to include Patient Specific Implants (PSI). This change in design paradigms needs advanced tools to assess the mechanical performance of the product, and simulate the impact on the patient. In this work, we perform a structural analysis on the interface of a cranial PSI under static loading conditions. Based on those simulations, we have identified the regions with high stress and strain and checked the failure criteria both in the implant and the skull. We evaluate the quality of the design of the implant and determine their response given different materials, in order to ensure optimality of the final product to be manufactured

Pasando revista : El Gráfico, Mundo Deportivo y Goles, tres maneras de narrar el deporte argentino del siglo XX

La historia del periodismo deportivo en Argentina está íntimamente ligada a la palabra impresa. Mucho antes de la aparición de la radio y la TV, fue el periodismo gráfico el primero en difundir la actividad deportiva. Durante el siglo XX, las revistas especializadas sentaron las bases de cómo narrar el deporte en Argentina. Esta ponencia buscará indagar en la forma en que lo hicieron algunas de las más importantes: El Gráfico, Mundo Deportivo y Goles. Cómo construyeron sus tapas y sus notas, qué información jerarquizaron y cuál descartaron, quiénes fueron los protagonistas de sus páginas y cómo pensaron a sus lectores son claves para recuperar el pasado del periodismo deportivo, entender el presente y proyectar el futur