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

Application of edible nanolaminate coatings with antimicrobial extract of Flourensia cernua to extend the shelf-life of tomato (Solanum lycopersicum L.) fruit

Supplementarymaterialrelatedtothisarticlecanbefound,inthe online version, at doi:https://doi.org/10.1016/j.postharvbio.2018.12. 008.Edible coatings have potential to reduce postharvest losses of fruit such as tomato. In this study, the effects of nanolaminate coatings incorporated with extracts of Flourensia cernua, an endemic plant of the arid and semi-arid regions of Mexico, has been investigated. Ethanol extracts of F. cernua (FcE) were prepared and incorporated into polyelectrolyte solutions of alginate and chitosan. The nanolaminates were characterized by determining the zeta potential, contact angle and water vapor and oxygen permeabilities. Shelf-life analyses (20°C for 15 d) were carried out with uncoated fruit (UCF), nanolaminate coating (NL) and nanolaminate coating with FcE (NL+FcE). Physicochemical analyses, gas exchange rates of O2 and CO2 and ethylene production, as well as microbiological analyses of treated fruit were measured. Zeta potential and contact angle measurements confirmed the successful assembly of successive nanolayers of alginate and chitosan, as well as those with F. cernua. The nanolaminate coatings resulted in decreased permeabilities to water and O2. The best treatment of NL+FcE, extended the shelf-life of fruit by reducing weight loss and microbial growth, reducing gas exchange and ethylene production, and maintaining firmness and color. The NL+FcE treatment are an alternative to extend the shelf-life of tomato fruit.Author E. de J. Salas-Méndez thanks Mexican Science and Technology Council (CONACYT, Mexico) for PhD fellowship support. Authors want to thank PhD Zlatina Genisheva for the proof reading of the manuscript and suggestions to the same; also, to:MaríaGuadalupe Moreno Esquivel, Edith E. Chaires Colunga, Olga L. Solís Hernández and M. Leticia Rodríguez González of the Phytochemistry Laboratory from Universidad Autónoma Agraria Antonio Narro, for their assistance in obtaining extracts and chemical composition.info:eu-repo/semantics/publishedVersio

Extractos de plantas del semidesierto en la inducción del crecimiento de tomate (Lycopersicon esculentum Mill)

ABSTRACT: In the semi-arid areas of northeastern Mexico, species with high polyphenol content and antioxidant activity have been identified, which can be used as growth and fruit quality promoters in tomato plants. The objective was to know the effect of Rhus trilobata, Rhus muelleri, Flourensia microphylla, Flourensia retinophylla and Cucurbita foetidissima extracts, as growth and fruit quality promoters in saladette tomato plants, when compared with bioregulators, AIA, AG and 6-BAP. The dose of the extract and bioregulator was 75 mg L-1, at the transplant and at 34 and 55 days after the transplant. Every fifteen days the longitudinal growth and stem diameter, number of leaves, number of fruits, dry weight, in addition to weight and fruit production were evaluated, in addition to the quality variables: polar and equatorial diameter, firmness, pH, soluble solids total, lycopene and vitamin C content. The experiment was established under a completely randomized design with nine treatments and 12 repetitions. In general, extracts increased stem length and diameter, dry leaf weight, number and weight of fruits, and fruit production, with results similar to the 6-BAP bioregulator. The extract of R. muelleri showed the greatest effectiveness in promoting the growth and production of tomato fruit, which is why it represents an alternative for the formulation of a bio-stimulant of biological origin that improves the productivity of tomato plants.RESUMEN: En las zonas semiáridas del noreste de México, se han identificado especies con alto contenido de polifenoles y actividad antioxidante, que pueden ser utilizadas como promotores de crecimiento y calidad del fruto en plantas de tomate. El objetivo fue conocer el efecto de extractos de Rhus trilobata, Rhus muelleri, Flourensia microphylla, Flourensia retinophylla y Cucurbita foetidissima, como promotores de crecimiento y calidad del fruto en plantas de tomate saladette, al compararlos con los biorreguladores AIA, AG y 6-BAP. La dosis del extracto y biorreguladores fue de 75 mg L-1, al trasplante, y a los 34 y 55 días después del trasplante. Cada quince días se evaluó el crecimiento longitudinal y diámetro de tallo, número de hojas, número de frutos, peso seco, peso y producción de fruto, además de las variables de calidad: diámetro polar y ecuatorial, firmeza, pH, sólidos solubles totales, contenido de licopeno y vitamina C. El experimento se estableció bajo un diseño completamente al azar con nueve tratamientos y 12 repeticiones. En general los extractos incrementaron la longitud y diámetro de tallo, peso seco de hojas, número y peso de frutos, y producción de fruto, con resultados similares al biorregulador 6-BAP. El extracto de R. muelleri mostró la mayor efectividad en promover el crecimiento y producción de fruto de tomate por lo que representa una alternativa para la formulación de un bioestimulante de origen biológico que mejore la productividad de las plantas de tomate

Black hake (Merluccius polli and M. senegalensis) off Mauritania: spatio-temporal distribution of two sympatric species. 1. Yields.

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Black hake (Merluccius polli and M. senegalensis) off Mauritania: spatio-temporal distribution of two sympatric species. 2. Population structure

Versión del edito

Prevalence of reduced lung diffusing capacity and CT scan findings in smokers without airflow limitation: a population-based study

Background Population distribution of reduced diffusing capacity of the lungs for carbon monoxide (DLCO) in smokers and main consequences are not properly recognised. The objectives of this study were to describe the prevalence of reduced DLCO in a population-based sample of current and former smoker subjects without airflow limitation and to describe its morphological, functional and clinical implications.Methods A sample of 405 subjects aged 40 years or older with postbronchodilator forced expiratory volume in 1 s/forced vital capacity (FVC) >0.70 was obtained from a random population-based sample of 9092 subjects evaluated in the EPISCAN II study. Baseline evaluation included clinical questionnaires, exhaled carbon monoxide (CO) measurement, spirometry, DLCO determination, 6 min walk test, routine blood analysis and low-dose CT scan with evaluation of lung density and airway wall thickness.Results In never, former and current smokers, prevalence of reduced DLCO was 6.7%, 14.4% and 26.7%, respectively. Current and former smokers with reduced DLCO without airflow limitation were younger than the subjects with normal DLCO, and they had greater levels of dyspnoea and exhaled CO, greater pulmonary artery diameter and lower spirometric parameters, 6 min walk distance, daily physical activity and plasma albumin levels (all p<0.05), with no significant differences in other chronic respiratory symptoms or CT findings. FVC and exhaled CO were identified as independent risk factors for low DLCO.Conclusion Reduced DLCO is a frequent disorder among smokers without airflow limitation, associated with decreased exercise capacity and with CT findings suggesting that it may be a marker of smoking-induced early vascular damage.Trial registration number NCT03028207