Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Thyroid volume measurement in external beam radiotherapy patients using CT imaging: correlation with clinical and anthropometric characteristics

International audienceThe aim of this study is to define criteria for accurate representation of the thyroid in human models used to represent external beam radiotherapy (EBRT) patients and evaluate the relationship between the volume of this organ and clinical and anthropometric characteristics. From CT images, we segmented the thyroid gland and calculated its volume for a population of 188 EBRT patients of both sexes, with ages ranging from 1 to 89 years. To evaluate uncertainties linked to measured volumes, experimental studies on the Livermore anthropomorphic phantom were performed. For our population of EBRT patients, we observed that in children, thyroid volume increased rapidly with age, from about 3 cm(3) at 2 years to about 16 cm(3) at 20. In adults, the mean thyroid gland volume was 23.5 ± 9 cm(3) for males and 17.5 ± 8 cm(3) for females. According to anthropometric parameters, the best fit for children was obtained by modeling the log of thyroid volume as a linear function of body surface area (BSA) (p < 0.0001) and age (p = 0.04) and for adults, as a linear function of BSA (p < 0.0001) and gender (p = 0.01). This work enabled us to demonstrate that BSA was the best indicator of thyroid volume for both males and females. These results should be taken into account when modeling the volume of the thyroid in human models used to represent EBRT patients for dosimetry in retrospective studies of the relationship between the estimated dose to the thyroid and long-term follow-up data on EBRT patients

Radiation doses to normal tissues and organs outside the target volume during radiotherapy

Public Health Codes more and more require that any information relevant to the estimation of the high doses delivered within the target volumes and low doses delivered outside should be recorded. In this context, the availability for each radiotherapy patient of the magnitude of the unavoidable low doses delivered outside the target-volumes becomes an important issue. However, to date, Treatment Planning Systems (TPS) are not designed for this issue. Therefore, we have developed a new version of the ISOgray TPS which can provide, in addition to the doses distributions in the fields, the magnitude of the doses to distant healthy tissues in the course of common radiotherapeutic procedures. Our strategy involves 3 modules: A library of adjustable whole-body patient models in treatment position which allows different patient anatomies to be simulated; A multi-sources beam model, which allows the description of the irradiation field to be extended to the whole body; A dose calculation engine producing the distributions of doses in the fields and in any organ outside. This paper describes the principles of the system and provides data on doses distributions to distant organs for various common radiotherapeutic procedures. At this stage of development, the agreement of measured and calculated doses reaches ±3% in the radiation field and is better than ±15% outside. In the case of a 17 years aged girl treated for Hodgkin's disease using two 6MV opposite photon beams, when a dose of 20 Gy was delivered to the target volume, outside the beam, the dose to the brain was 0.37 Gy (1.85% of the tumor dose), the kidney 0.06 Gy (0.30%) and the ovaries below 0.02 Gy (<0.1%). Although the development of our system is still in progress, these preliminary results are encouraging. Allowing the realization of whole-body dose evaluations for each patient in the course of radiation therapy treatment planning, our approach must provide relevant information required to meet the current requirements of patient radiation protection and radiation therapy benefit-risk management purposes. The systematic evaluation of low doses outside the radiation therapy fields creates new opportunities in quality assurance of radiation therapy and prospective studies of long-term risks of radiation modern radiotherapeutic procedures

Migration of surface-associated microbial communities in spaceflight habitats

Astronauts are spending longer periods locked up in ships or stations for scientific and exploration spatial missions. The International Space Station (ISS) has been inhabited continuously for more than 20 years and the duration of space stays by crews could lengthen with the objectives of human presence on the moon and Mars. If the environment of these space habitats is designed for the comfort of astronauts, it is also conducive to other forms of life such as embarked microorganisms. The latter, most often associated with surfaces in the form of biofilm, have been implicated in significant degradation of the functionality of pieces of equipment in space habitats. The most recent research suggests that microgravity could increase the persistence, resistance and virulence of pathogenic microorganisms detected in these communities, endangering the health of astronauts and potentially jeopardizing long-duration manned missions. In this review, we describe the mechanisms and dynamics of installation and propagation of these microbial communities associated with surfaces (spatial migration), as well as long-term processes of adaptation and evolution in these extreme environments (phenotypic and genetic migration), with special reference to human health. We also discuss the means of control envisaged to allow a lasting cohabitation between these vibrant microscopic passengers and the astronauts