Generation of mice with longer and better preserved telomeres in the absence of genetic manipulations

Although telomere length is genetically determined, mouse embryonic stem (ES) cells with telomeres of twice the normal size have been generated. Here, we use such ES cells with 'hyper-long' telomeres, which also express green fluorescent protein (GFP), to generate chimaeric mice containing cells with both hyper-long and normal telomeres. We show that chimaeric mice contain GFP-positive cells in all mouse tissues, display normal tissue histology and normal survival. Both hyper-long and normal telomeres shorten with age, but GFP-positive cells retain longer telomeres as mice age. Chimaeric mice with hyper-long telomeres also accumulate fewer cells with short telomeres and less DNA damage with age, and express lower levels of p53. In highly renewing compartments, such as the blood, cells with hyper-long telomeres are longitudinally maintained or enriched with age. We further show that wound-healing rates in the skin are increased in chimaeric mice. Our work demonstrates that mice with functional, longer and better preserved telomeres can be generated without the need for genetic manipulations, such as TERT overexpression.M. A. Blasco’s laboratory is funded by the Spanish Ministry of Economy and Competitiveness Project SAF2013-45111RETOS, the European Union FP7 Project EUROBATS, the European Research Council (ERC) Project TEL STEM CELL (GA#232854), the Regional Government of Madrid 2þ2 ReCaRe, the AXA Research Fund and the Fundacion BotınS

Histoire et recherche pour la paix. Expériences autour de la Méditerranée

Ce travail aborde une série d’apports théoriques et méthodologiques que nous considérons intéressants pour la recherche historique. Parmi les premiers, il convient de souligner un tournant ontologique et épistémologique qui permet de situer la paix au cœur de notre recherche. Parmi les seconds, la proposition d’une matrice unitaire et compréhensible composée de cinq axes reliés : une théorie générale des conflits ; la réflexion autour d’une paix imparfaite ; la déconstruction de la violence ; la distinction entre les médiations et les interactions systémiques entre conflits, paix et violence ; et l’empowerment pacifiste. Suivant cette approche, nous abordons trois aspects du présent : l’évolution de l’Indice de Développement Humain, les mouvements des indignés et le printemps arabe et la participation au sein de la plateforme Avaaz.org. Les résultats indiquent que maintenant, et malgré les violences générées, la Méditerranée est une réalité historique plus pacifique qu’il y a trente-cinq ans.In this paper, we focus on a set of theoretical and methodological approaches that we consider relevant for History. From a theoretical point of view we emphasize the necessity of an ontological and epistemological turn which permit us to place peace in the core of our research. From the methodological one, we propose a comprehensive and integrative matrix shaped by five intertwined focuses: a general theory of conflicts; a reflection on an imperfect system of peace; a deconstruction of all forms of violence; a distinction between power of mediations and systemic interactions between conflicts, peace and violence; and pacifistic empowerment. Following this approach, we make a preliminary analysis of three aspects of contemporary Mediterranean: the evolution of the Human Development Index, the social movements known as indignados (indignants) and Arab Spring, and the participation in Avaaz.org. Our results show that in spite of the multiple violences generated through the Mediterranean Sea, this historical region is more pacific now than it was 35 years ago

Transgenerational inheritance of environmental information in Caenorhabditis elegans

Motivation: In 1906 Luther Burbank, an American botanist, said “Heridity is only the sum of all past environment” (Burbank, 1906). This idea has always been present in spite of being left behind after sustaining that the germline was isolated of the rest of the organism and, therefore, of the environment. With the rediscovery of epigenetics as a regulatory system which controls gene expression without affecting the composition of genes themselves, this idea has regained importance. Not only a great number of cases of environmental changes that influenced the epigenetics in a great variety of species began to be observed; but also the effects of these changes could last for three or more generations. This phenomenon was known as transgenerational epigenetic inheritance (Heard and Martienssen, 2014). This project aims to study the phenomenon of transgenerational epigenetic inheritance in the Caenorhabditis elegans model animal. The idea is to set the parameters where we can identify the phenomenon and reveal the molecular mechanism involved in the process.Methods: We set two different experiments, resistance to pathogen and behavioral respond to the pathogen. For the resistance experiment, plates with Escherichia coli (OP50, main source of nematode's food) and plates with Pseudomonas aeruginosa (PA14, a pathogen) were used to grow mothers and then the percentage of descendants that reach adulthood were scored. For the behavioral experiment, plates with OP50 and plates with both bacteria (PA14 and OP50) were used to grow mothers. Then their eggs were placed on plates containing OP50 and PA14. We counted the percent of worms that went to OP50 and to PA14.Results: It has been observed that individuals whose mothers have been exposed to Pseudomonas aeruginosa are more resistant to it than those whose mothers have never been in contact with the pathogen. On the other hand, it has been observed that this inheritance not only affects the defense mechanisms of the organism, but also influences its behavior. At this time we are studying the genetic pathways involved in this process by using mutants affected in epigenetic and in other candidate pathways.Conclusions: Our results suggest that there is not only an inheritance to stress resistance but also an acquired behavioral inheritance. Genes involved in epigenetic seem to be involved in the process

Radical radiotherapy in epidermoid cancer in the orbitary region: ideal scheme of hypo-fractionation in times of COVID-19: a case report

There are adverse events in the patient's environment that impact on therapeutic decisions and become a medical challenge, as is currently the management of cancer patients with radiotherapy, particularly the elderly in times of a COVID-19 pandemic, due the high risk of infection and fatal complications from non-cancer causes. Here we present the case of an 84-year-old woman with voluminous squamous cell cancer in the left orbital region, which caused intense pain, stench, and persistent bleeding. And due to persistence and time, it impacted with deterioration in the patient’s quality of life. In the end, of hypo fractionated radiotherapy management as the only modality, it evolves with a complete clinical response and total palliation of initial symptoms. The reasons for the decision to manage radiotherapy and the excellent clinical results that reinforce the idea of personalized medicine and the importance of evaluating the biopsychosocial environment of the cancer patient will be discussed

Paper-based chromatic toxicity bioassay by analysis of bacterial ferricyanide reduction

Water quality assessment requires a continuous and strict analysis of samples to guarantee compliance with established standards. Nowadays, the increasing number of pollutants and their synergistic effects lead to the development general toxicity bioassays capable to analyse water pollution as a whole. Current general toxicity methods, e.g. Microtox®, rely on long operation protocols, the use of complex and expensive instrumentation and sample pre-treatment, which should be transported to the laboratory for analysis. These requirements delay sample analysis and hence, the response to avoid an environmental catastrophe. In an attempt to solve it, a fast (15 min) and low-cost toxicity bioassay based on the chromatic changes associated to bacterial ferricyanide reduction is here presented. E. coli cells (used as model bacteria) were stably trapped on low-cost paper matrices (cellulose-based paper discs, PDs) and remained viable for long times (1 month at -20 °C). Apart from bacterial carrier, paper matrices also acted as a fluidic element, allowing fluid management without the need of external pumps. Bioassay evaluation was performed using copper as model toxic agent. Chromatic changes associated to bacterial ferricyanide reduction were determined by three different transduction methods, i.e. (i) optical reflectometry (as reference method), (ii) image analysis and (iii) visual inspection. In all cases, bioassay results (in terms of half maximal effective concentrations, EC50) were in agreement with already reported data, confirming the good performance of the bioassay. The validation of the bioassay was performed by analysis of real samples from natural sources, which were analysed and compared with a reference method (i.e. Microtox). Obtained results showed agreement for about 70% of toxic samples and 80% of non-toxic samples, which may validate the use of this simple and quick protocol in the determination of general toxicity. The minimum instrumentation requirements and the simplicity of the bioassay open the possibility of in-situ water toxicity assessment with a fast and low-cost protocolPostprint (author's final draft

Estudio de las lesiones neoplásicas metacrónicas en el carcinoma colorrectal

Fundamento. Analizar la frecuencia y las características de las lesiones neoplásicas metacrónicas, carcinomas y adenomas, tras la resección de un cáncer colo-rectal (CCR). Pacientes y métodos. Revisamos 382 CCR operados y seguidos mediante colonoscopias completas en dos hospitales de nuestra comunidad. Analizamos las lesiones metacrónicas registradas valorando su localización, momento del diagnóstico, histología, número y tamaño. Estudiamos la frecuencia de adenomas de aparición precoz (12 meses), comparando su tamaño con respecto al resto de lesiones. Resultados. La mediana de seguimiento fue de 48 meses (12-112), con 2,74±1,47 colonoscopias/caso. Diagnosticamos 7 cánceres metacrónicos (1,8%), 4 de ellos en estadio I. La mediana de tiempo hasta su diagnóstico fue de 24 meses (13-54). Registramos adenomas metacrónicos en 162 casos (42,4%), sin diferencias entre los dos hospitales: 42,1% vs. 43,8% (p=0,88). Un 6,3% de los pacientes presentaron adenomas avanzados. En 164 casos en que el primer control se efectuó a los 12 meses, la incidencia de adenomas fue del 24%. Los adenomas fueron mayoritariamente únicos (60,8%) y menores de 5 mm (68,5%). En un 55,5% de los casos con pólipos, alguno tenía una localización proximal. El diagnóstico se realizó en la 1ª exploración (56,2%), 2ª (27,8%) ó 3ª (9%). La mediana de tiempo hasta el diagnóstico fue de 21 meses (12-112) para el adenoma simple y de 35 (12-112) para el avanzado. Conclusiones. Nuestro seguimiento permitió aplicar un tratamiento teóricamente curativo en la mayoría de los carcinomas metacrónicos diagnosticados. La alta incidencia de adenomas y su frecuente localización proximal hacen necesario un seguimiento con colonoscopias completas, que debería iniciarse al año de la operación y podría pasar a ser menos estricto tras tres exploraciones consecutivas sin pólipos