DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7x10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95% CI: 1.03-1.21, p = 4.8x10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied

Posttraumatic growth in cancer survivors and their significant others: vicarious or secondary growth?

Las enfermedades graves como el cáncer, aunque generan elevado malestar emocional y estrés en los supervivientes y en sus otros significativos, también pueden suponer un estímulo en la generación de crecimiento postraumático en ambos. Los mecanismos de cómo se produce este crecimiento postraumático (vicario vs. secundario) en los otros significativos no se han estudiado. En esta revisión se analizan la evidencia y relación del crecimiento post-traumático en supervivientes de cáncer y en sus otros significativos, principalmente sus parejas, madres y padres, en relación a estos mecanismos de transmisión vicario o secundario. Se concluye que, en general, el crecimiento post-traumático en los otros significativos es una experiencia vicaria íntimamente ligada al crecimiento del superviviente en cáncer, aunque ser mujer, madre o sufrir un cáncer avanzado facilitan procesos de crecimiento post-traumático secundario en los otros significativos, que se diferencian del superviviente

Diseño y estudio de viabilidad de una microcervecería artesanal

El presente proyecto surge como iniciativa propia a la hora de desvelar la incógnita sobre la viabilidad de una microcervecería en entorno de la provincia de Zaragoza y diseñarla. La elección de la provincia de Zaragoza como ubicación de la citada industria se debe a que únicamente existen dos plantas de este tipo en la zona (en Aragón existen 13 microcervecerías). Por este motivo, cabe suponer que este campo de mercado todavía se encuentra en vías tempranas de desarrollo, lo que podría favorecer el asentamiento de una nueva planta en el corto medio plazo. La industria se sitúa en una nave propiedad del promotor, la cual se ha adaptado al proceso productivo de la cerveza artesanal. Se ha realizado un estudio detallado de la línea de producción, prestando especial detalle a las necesidades térmicas de la industria. También se han descrito las instalaciones de fontanería, saneamiento y las instalaciones eléctricas. La pequeña planta se ha diseñado para poder producir anualmente 48.000 litros de cerveza que se distribuirán en botellas de 0,33 l. Es estudio de viabilidad económica demuestra que comercializando la totalidad de la producción ofrece rendimientos económicos positivos para una vida útil de 25 años

Genetic and demographic recovery of an isolated population of brown bear Ursus arctos L., 1758

The brown bear Ursus arctos L., 1758 population of the Cantabrian Mountains (northwestern Spain) became isolated from other bear populations in Europe about 500 years ago and has declined due to hunting and habitat degradation. At the beginning of the 20th century, the Cantabrian population split into eastern and western subpopulations, and genetic exchange between them ceased. In the early 1990s, total population size was estimated to be < 100 bears. Subsequently, reduction in human-caused mortality has brought about an increase in numbers, mainly in the western subpopulation, likely promoting male-mediated migration and gene flow from the western nucleus to the eastern. To evaluate the possible genetic recovery of the small and genetically depauperate eastern subpopulation, in 2013 and 2014 we genotyped hair and faeces samples (116 from the eastern subpopulation and 36 from the western) for 18 microsatellite markers. Data from the annual count of females with cubs of the year (COY) during the past twenty-six years was used to analyze demographic changes. The number of females with COY fell to a minimum of seven in the western and three in eastern subpopulations in the biennium 1993¿1994 and reached a respective maximum of 54 and 10 individuals in 2013¿2014. We also observed increased bear dispersal and gene flow, mainly from the western to the eastern subpopulation. Of the 26 unique genotypes detected in the eastern subpopulation, 14 (54%) presented an admixture composition, and seven (27%) were determined to be migrants from the western subpopulation. Hence, the two separated and clearly structured subpopulations identified in the past currently show some degree of genetic admixture. This research shows the partial demographic recovery and a change in genetic composition due to migration process in a population of bears that has been isolated for several centuriesPeer Reviewe

Verrucous epidermal nevus as a manifestation of a type 2 mosaic PTEN mutation in Cowden syndrome

Altres ajuts: Acord transformatiu CRUE-CSICUTP en procés de revisióLinear Cowden nevus, also known as linear PTEN nevus, is a type of epidermal nevus, first described in 2007, which is seen in patients with PTEN hamartoma tumor syndrome. It is considered to be a type 2 form of segmental mosaicism, and we suggest that it has certain clinical features that distinguish it from epidermal nevi seen in similar conditions, such as Proteus syndrome. We present a case of linear Cowden nevus in a 4-year-old boy and review the literature

A mild neurofibromatosis type 1 phenotype produced by the combination of the benign nature of a leaky NF1-splice mutation and the presence of a complex mosaicism

Here we analyze the genetic and molecular basis responsible for a very benign phenotype observed in an NF1 patient. Quantification of cells carrying the NF1 mutation in different samples derived from the three embryonic layers revealed mosaicism. Furthermore, the construction of a minigene with patient's mutation (c.3198 − 314G>A) confirmed its benign nature due to the leakiness of the splicing mechanism that generated a proportion of correctly spliced transcripts. Hence, we concluded that the mild phenotype observed in this patient is the result of the presence of mosaicism together with the benign nature of a leaky NF1-splice mutation. Finally, with the aim of developing a personalized therapeutic approach for this patient, we demonstrated correction of the splicing defect by using specific antisense morpholino oligomers. Our results provide an example of the molecular complexity behind disease phenotypes and highlight the importance of using comprehensive genetic approaches to better assess phenotype-genotype correlation

Mediación y arbitraje en conflictos derivados de la actividad investigadora y de transferencia

Esta publicación constituye una muestra de la firme voluntad de cooperación existente entre el Parc Científic de la Universitat de València y la Corte de Arbitraje y Mediación de Valencia, en un ámbito que adolece de estudios que aúnen la necesidad de profundidad y de practicidad. Para ello, se ha contado con un valioso elenco de académicos y de profesionales que ponen en valor sus conocimientos y experiencia, con el objeto de ofrecer claves para prevenir y evitar los posibles conflictos que pueden producirse en el marco de este tipo de acuerdos, así como, llegado el caso, reducir su intensidad y favorecer una gestión adecuada de los mismos; ofreciendo valiosas recomendaciones dirigidas a investigadores y a responsables de las unidades de trasferencia de resultados de investigación de las Universidades y de los Centros de Investigación, así como a gestores y profesionales que intervienen en los proyectos de I+D+i

Modelo bidimensional de inundación urbana de la ciudad de Azul (Argentina) con herramientas de uso libre

En la actualidad, la simulación de inundaciones con modelos matemáticos para las ecuaciones de Saint Venant (o de aguas poco profundas) tanto en 1D como en 2D cuenta con un gran número de códigos para su ejecución, pero no son tantos los códigos robustos y de uso libre. Se ha empleado uno de ellos: el software IBER y se ha validado el modelo mediante la reproducción de la inundación de mayo de 2012 en la ciudad de Azul (Argentina). Se describen los procedimientos empleados para la construcción del MDT en el cauce y el valle de inundación en el entorno urbano; la obtención del mallado eficiente en el dominio; la ejecución del IBER con las distintas configuraciones y parámetros; la inclusión de puentes, los tiempos de ejecución, etc. Se ha puesto a punto la metodología de trabajo, se han detectado las principales precauciones a tomar para abordar con éxito este tipo de estudios y se ha verificado la aplicabilidad del software en zonas llanas. Los valores preliminares de calados y velocidades del flujo obtenidos para la ciudad de Azul, son datos útiles para la gestión del riesgo de inundación.Currently, the simulation of floods with mathematical models for the Saint Venant equations (or shallow water) in both 1D and 2D has a large number of codes for its execution, but there are not so many robust and free use codes available. IBER free-use software has been used and the model has been validated by reproducing the flood extent of May 2012 in the city of Azul (Argentina). The procedures used for the construction of the DTM in the channel and the flood plain including an urban environment are described; an efficient meshing for the representative domain; the execution of the IBER with different configurations and parameters; the inclusion of bridges, execution times, etc. The work methodology has been prepared, the main precautions to be taken to successfully address this type of studies have been detected and the applicability of the software in flat areas has been verified. The simulated values of depth and flow velocities obtained for the city of Azul are useful data for flood risk management

Geographical distribution of COPD prevalence in Europe, estimated by an inverse distance weighting interpolation technique

Existing data on COPD prevalence are limited or totally lacking in many regions of Europe. The geographic information system inverse distance weighted (IDW) interpolation technique has proved to be an effective tool in spatial distribution estimation of epidemiological variables, when real data are few and widely separated. Therefore, in order to represent cartographically the prevalence of COPD in Europe, an IDW interpolation mapping was performed. The point prevalence data provided by 62 studies from 19 countries (21 from 5 Northern European countries, 11 from 3 Western European countries, 14 from 5 Central European countries, and 16 from 6 Southern European countries) were identified using validated spirometric criteria. Despite the lack of data in many areas (including all regions of the eastern part of the continent), the IDW mapping predicted the COPD prevalence in the whole territory, even in extensive areas lacking real data. Although the quality of the data obtained from some studies may have some limitations related to different confounding factors, this methodology may be a suitable tool for obtaining epidemiological estimates that can enable us to better address this major public health problem

Detection of SARS-CoV-2 in a cat owned by a COVID-19−affected patient in Spain

COVID-19 is the most devastating pandemic in recent history. As with many emerging infectious diseases, it is of zoonotic origin, meaning that animals played a major role in the initial transmission events. Despite SARS-CoV-2 being highly adapted to jump from human to human, several animal species are naturally susceptible to SARS-CoV-2, including pets such as cats. In the present report, a cat from a family with several relatives affected by COVID-19 developed severe respiratory clinical signs, leading to humanitarian euthanasia. Due to the suspicion of a potential COVID-19 infection in the cat, different antemortem and postmortem tests were assayed. The clinical condition was finally attributed to a feline hypertrophic cardiomyopathy, but the animal was also infected by SARS-CoV-2. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is considered a zoonotic pathogen mainly transmitted human to human. Few reports indicate that pets may be exposed to the virus. The present report describes a cat suffering from severe respiratory distress and thrombocytopenia living with a family with several members affected by COVID-19. Clinical signs of the cat prompted humanitarian euthanasia and a detailed postmortem investigation to assess whether a COVID-19−like disease was causing the condition. Necropsy results showed the animal suffered from feline hypertrophic cardiomyopathy and severe pulmonary edema and thrombosis. SARS-CoV-2 RNA was only detected in nasal swab, nasal turbinates, and mesenteric lymph node, but no evidence of histopathological lesions compatible with a viral infection were detected. The cat seroconverted against SARS-CoV-2, further evidencing a productive infection in this animal. We conclude that the animal had a subclinical SARS-CoV-2 infection concomitant to an unrelated cardiomyopathy that led to euthanasia