Perceptive approaches to the morphological characterization of the urban contour: The case of the peri-urban landscape of Madrid

[EN] A growing city adapts and transforms the pre-existing topography, and with its urban fabric defines an ever-changing contour throughout history; this contour is not a clear line, but rather a fringe, where city and countryside meet and create occupancy systems that are crucial to comprehend the evolution of the urban form. We can consider this fringe as ‘proximity’ landscapes: landscapes that are perceived when the city is either a destination or a point of departure. The vision from afar, or when progressively approaching the city, provides both locals and tourists with certain landscape and architectural aspects that should be studied, preserved and valued for their ability to generate meaningful spaces. In this communication we study the surrounding landscapes of Madrid by means of a Landscape Character Assessment, within the framework of the project ‘Proximity landscapes of the city of Madrid. From the 19thC to the present’ currently in process. Combining graphic analysis of historical cartography at a metropolitan scale with perceptive analysis techniques, special attention is drawn to certain axes and significant lookouts of the city, mapping them and evaluating their visual basins. This characterization leads to distinguishing three main landscape types surrounding Madrid, according to physical, natural and anthropogenic structures: one predominantly natural, one mainly industrial and service-related, and a third one with special historical relevance.This research has been developed in the framework of the State Plan Project of the Ministry of Economy and Competitiveness (HAR2014-57843-R), entitled “Proximity Landscapes of the City of Madrid. From the 19th Century to the present”. We thank the General Secretariat of Science, Technology and Innovation for the funding of this project. Likewise, we thank the Spanish Ministry of Education for the pre-doctoral scholarship (FPU14/05524) granted to co-author Carlota Sáenz de Tejada Granados in its FPU Program. Lastly, we thank San Pablo-CEU University Foundation for the pre-doctoral scholarship granted to co-author Rocío Santo-Tomás Muro in its FPI Program.Rodríguez Romero, E.; Sáenz De Tejada Granados, C.; Santo-Tomás Muro, R. (2018). Perceptive approaches to the morphological characterization of the urban contour: The case of the peri-urban landscape of Madrid. En 24th ISUF International Conference. Book of Papers. Editorial Universitat Politècnica de València. 1349-1358. https://doi.org/10.4995/ISUF2017.2017.5345OCS1349135

Influence of energy paradigm shifts on city boundaries. The productive peripheries of Madrid

[EN] The promotion or access to certain energy technologies has changed the humanized landscape throughout history; cities have been born around, and because of an energy source, or have been displaced in order for energy-related infrastructures to take their spot. However, and for any city from its very beginning, energy paradigm shifts have deeply altered their morphology. Not only extraction, but especially transformation and transport of resources materializes in artefacts, often controversial and soon-to-be obsolete. This is especially patent in the ever-changing city boundaries; the fringe of ‘proximity’, where the collision between the countryside and the urban mesh embodies the relations and contradictions between urban growth, energy demand and landscape protection. In a context of growing cities (both in terms of expansion of its artificial land and in terms of energy demand), we are facing two paths which not always converge: an inevitable low carbon transition and a growing sensitivity towards ordinary landscapes. This article, within the framework of the project ‘Proximity landscapes of the city of Madrid. From the 19thC to the present’, studies the development of the city of Madrid in relation to its energy access and management, in a series of key stages: mid-19thC (before the bourgeois enlargement plan approved in 1860), early 20thC (when the introduction of electricity powered a deep urban transformation and outlaying urban cores were annexed), mid-late 20thC (when a rural exodus took place and the peripheries of Madrid grew rapidly) and today.This research has been developed in the framework of the State Plan Project of the Ministry of Economy and Competitiveness (HAR2014-57843-R), entitled “Proximity Landscapes of the City of Madrid. From the 19th Century to the present”. We thank the General Secretariat of Science, Technology and Innovation for the funding of this project. Likewise, we thank the Spanish Ministry of Education for the pre-doctoral scholarship (FPU14/05524) granted to co-author Carlota Sáenz de Tejada Granados in its FPU Program. Lastly, we thank San Pablo-CEU University Foundation for the pre-doctoral scholarship granted to co-author Rocío Santo-Tomás Muro in its FPI Program.Sáenz De Tejada Granados, C.; Rodríguez Romero, E.; Santo-Tomás Muro, R. (2018). Influence of energy paradigm shifts on city boundaries. The productive peripheries of Madrid. En 24th ISUF International Conference. Book of Papers. Editorial Universitat Politècnica de València. 719-128. https://doi.org/10.4995/ISUF2017.2017.5343OCS71912

The role of historical green spaces in the identity and image of today’s cities: The case of Madrid

[EN] The image that a city offers when approaching it, depending on its topographical situation, the drawing of its borders or its urban form, generates a perceptive construction, for both locals and tourists, with the potential to become an iconic image and therefore play a part in the collective imagery. The character and value of those landscapes is largely determined by their green spaces, preserved in most European cities for their ecological or historical significance. Being able to recognize the worthiness of these proximity visions, in the context of today’s growing cities, is of fundamental relevance in order to enhance the sense of place, amongst other community values. In this communication we study the above-mentioned aspects in the image of the city of Madrid, within the framework of the project ‘Proximity landscapes of the city of Madrid. From the 19thC to the present’ currently in process. Through a landscape analysis of a selection of iconographic representations of the surroundings of the city, we draw special attention to the presence of historical green spaces throughout time, and its relation with architectural landmarks in the progressive construction of an iconic image of the city. From here, we can deduce the relevance that these elements have in the generation of a recognizable character and the decisive role of protection mechanisms in order to preserve it.This research has been developed in the framework of the State Plan Project of the Ministry of Economy and Competitiveness (HAR2014-57843-R), entitled “Proximity Landscapes of the City of Madrid. From the 19th Century to the present”. We thank the General Secretariat of Science, Technology and Innovation for the funding of this project. Likewise, we thank the Spanish Ministry of Education for the pre-doctoral scholarship (FPU14/05524) granted to co-author Carlota Sáenz de Tejada Granados in its FPU Program. Lastly, we thank San Pablo-CEU University Foundation for the pre-doctoral scholarship granted to co-author Rocío Santo-Tomás Muro in its FPI Program.Rodríguez Romero, E.; Sáenz De Tejada Granados, C.; Santo-Tomás Muro, R. (2018). The role of historical green spaces in the identity and image of today’s cities: The case of Madrid. En 24th ISUF International Conference. Book of Papers. Editorial Universitat Politècnica de València. 1647-1656. https://doi.org/10.4995/ISUF2017.2017.5340OCS1647165

Implementación de sistema de gestión de la calidad en la empresa Krear GIP

El objetivo del proyecto fue la Formulación del Proyecto para la implementación de un Sistema de Gestión de Calidad en la empresa Krear GIP, ubicada en la ciudad de Yopal; perdió clientes debido a las fallas en los procesos. Este proyecto utilizó la investigación de campo como método de investigación y usos del análisis contextual, entrevistas, reuniones y documentales. revisar como herramientas para la recopilación de información; Para obtener los datos necesarios que permitieron. ejecutar las cinco fases de la implementación, involucrando constantemente a las partes interesadas de El proyecto y garantizando su sostenibilidad. De esta manera, la empresa logró la La implementación del SGC de una manera exitosa, porque los clientes se incrementaron, se contrató más personal de trabajo, se incrementaron los ingresos y una mayor participación en Se obtuvo el mercado de la consultaría

Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency

The ATM kinase is a master regulator of the DNA damage response to double-strand breaks (DSBs) and a well-established tumour suppressor whose loss is the cause of the neurodegenerative and cancer-prone syndrome Ataxia-Telangiectasia (A-T). A-T patients and Atm−/− mouse models are particularly predisposed to develop lymphoid cancers derived from deficient repair of RAG-induced DSBs during V(D)J recombination. Here, we unexpectedly find that specifically disturbing the repair of DSBs produced by DNA topoisomerase II (TOP2) by genetically removing the highly specialised repair enzyme TDP2 increases the incidence of thymic tumours in Atm−/− mice. Furthermore, we find that TOP2 strongly colocalizes with RAG, both genome-wide and at V(D)J recombination sites, resulting in an increased endogenous chromosomal fragility of these regions. Thus, our findings demonstrate a strong causal relationship between endogenous TOP2-induced DSBs and cancer development, confirming these lesions as major drivers of ATM-deficient lymphoid malignancies, and potentially other conditions and cancer types.Junta de Andalucía SAF2010-21017, SAF2013-47343-P, SAF2014-55532-R, SAF2017-89619-R, CVI-7948European Research Council ERC-CoG-2014-64735

TDP2-Dependent Non-Homologous End-Joining Protects against Topoisomerase II-Induced DNA Breaks and Genome Instability in Cells and In Vivo

Anticancer topoisomerase >poisons> exploit the break-and-rejoining mechanism of topoisomerase II (TOP2) to generate TOP2-linked DNA double-strand breaks (DSBs). This characteristic underlies the clinical efficacy of TOP2 poisons, but is also implicated in chromosomal translocations and genome instability associated with secondary, treatment-related, haematological malignancy. Despite this relevance for cancer therapy, the mechanistic aspects governing repair of TOP2-induced DSBs and the physiological consequences that absent or aberrant repair can have are still poorly understood. To address these deficits, we employed cells and mice lacking tyrosyl DNA phosphodiesterase 2 (TDP2), an enzyme that hydrolyses 5′-phosphotyrosyl bonds at TOP2-associated DSBs, and studied their response to TOP2 poisons. Our results demonstrate that TDP2 functions in non-homologous end-joining (NHEJ) and liberates DSB termini that are competent for ligation. Moreover, we show that the absence of TDP2 in cells impairs not only the capacity to repair TOP2-induced DSBs but also the accuracy of the process, thus compromising genome integrity. Most importantly, we find this TDP2-dependent NHEJ mechanism to be physiologically relevant, as Tdp2-deleted mice are sensitive to TOP2-induced damage, displaying marked lymphoid toxicity, severe intestinal damage, and increased genome instability in the bone marrow. Collectively, our data reveal TDP2-mediated error-free NHEJ as an efficient and accurate mechanism to repair TOP2-induced DSBs. Given the widespread use of TOP2 poisons in cancer chemotherapy, this raises the possibility of TDP2 being an important etiological factor in the response of tumours to this type of agent and in the development of treatment-related malignancy.Gobierno Español SAF2010-21017, BFU2010-11042-EEuropean Union PERG07- 2010-268466Queen Elisabeth Medical Foundation GSKE 111

Postnatal Proteasome Inhibition Induces Neurodegeneration and Cognitive Deficiencies in Adult Mice: A New Model of Neurodevelopment Syndrome

Defects in the ubiquitin-proteasome system have been related to aging and the development of neurodegenerative disease, although the effects of deficient proteasome activity during early postnatal development are poorly understood. Accordingly, we have assessed how proteasome dysfunction during early postnatal development, induced by administering proteasome inhibitors daily during the first 10 days of life, affects the behaviour of adult mice. We found that this regime of exposure to the proteasome inhibitors MG132 or lactacystin did not produce significant behavioural or morphological changes in the first 15 days of life. However, towards the end of the treatment with proteasome inhibitors, there was a loss of mitochondrial markers and activity, and an increase in DNA oxidation. On reaching adulthood, the memory of mice that were injected with proteasome inhibitors postnatally was impaired in hippocampal and amygdala-dependent tasks, and they suffered motor dysfunction and imbalance. These behavioural deficiencies were correlated with neuronal loss in the hippocampus, amygdala and brainstem, and with diminished adult neurogenesis. Accordingly, impairing proteasome activity at early postnatal ages appears to cause morphological and behavioural alterations in adult mice that resemble those associated with certain neurodegenerative diseases and/or syndromes of mental retardation

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Lack of TDP2 causes etoposide-induced hematologic toxicity and genome instability in mice

Póster presentado al 22nd IUBMB & 37th FEBS Congress: From Single Molecules to Systems Biology, celebrado en Sevilla (España) del 4 al 9 de septiembre de 2012Peer Reviewe

TDP2-Dependent Non-Homologous End-Joining Protects against Topoisomerase II-Induced DNA Breaks and Genome Instability in Cells and In Vivo

Gómez-Herreros, Fernando et al.Anticancer topoisomerase >poisons> exploit the break-and-rejoining mechanism of topoisomerase II (TOP2) to generate TOP2-linked DNA double-strand breaks (DSBs). This characteristic underlies the clinical efficacy of TOP2 poisons, but is also implicated in chromosomal translocations and genome instability associated with secondary, treatment-related, haematological malignancy. Despite this relevance for cancer therapy, the mechanistic aspects governing repair of TOP2-induced DSBs and the physiological consequences that absent or aberrant repair can have are still poorly understood. To address these deficits, we employed cells and mice lacking tyrosyl DNA phosphodiesterase 2 (TDP2), an enzyme that hydrolyses 5′-phosphotyrosyl bonds at TOP2-associated DSBs, and studied their response to TOP2 poisons. Our results demonstrate that TDP2 functions in non-homologous end-joining (NHEJ) and liberates DSB termini that are competent for ligation. Moreover, we show that the absence of TDP2 in cells impairs not only the capacity to repair TOP2-induced DSBs but also the accuracy of the process, thus compromising genome integrity. Most importantly, we find this TDP2-dependent NHEJ mechanism to be physiologically relevant, as Tdp2-deleted mice are sensitive to TOP2-induced damage, displaying marked lymphoid toxicity, severe intestinal damage, and increased genome instability in the bone marrow. Collectively, our data reveal TDP2-mediated error-free NHEJ as an efficient and accurate mechanism to repair TOP2-induced DSBs. Given the widespread use of TOP2 poisons in cancer chemotherapy, this raises the possibility of TDP2 being an important etiological factor in the response of tumours to this type of agent and in the development of treatment-related malignancy. © 2013 Gómez-Herreros et al.Work in FC-L laboratory is funded with grants from the Spanish Government (SAF2010-21017 and BFU2010-11042-E) and the European Union (PERG07- 2010-268466) and with the following fellowships from the Spanish Government: Ramo´n y Cajal (RYC-2009-03928) for FC-L, JAE-Doc (2010-011) for RR-G, and FPI (BES-2011-047351) for A´A-Q. Work in the KWC laboratory is funded by MRC grants to KWC (G0901606, G0600776, MR/J006750/1) and supported FG-H, ZZ, and LJ. Generation of the Tdp2 floxed and conditional mice in the DH lab was supported by the EC FP6 Integrated Project EndoTrack, the Interuniversity Attraction Pole IUAP-P6/20 and P7/07 project, and the Queen Elisabeth Medical Foundation (GSKE 1113) and type 3 large-infrastructure support InfraMouse (Hercules Foundation ZW09-03, to DH).Peer Reviewe