Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

Synchrotron Stereotactic Radiation Therapy: A Report on Phase 1/2 Clinical Trial Achievements, Ongoing Developments, and Long-Term Prospects

International audienceTherapeutic applications of synchrotron X rays are becoming a reality. The first phase I/II clinical study of synchrotron stereotactic radiation therapy (SSRT) consists of a dose-escalation protocol to show the feasibility and safety of the technique. Oligo-brain-metastatic patients have been irradiated since June 2012 using 80 keV high-flux quasiparallel monochromatic x-ray beams, in the presence of iodinated compounds injected immediately before irradiation. A localized dose enhancement occurs in the target at this energy, due to the photoelectric effect

Accounting for artificial light impact on bat activity for a biodiversity-friendly urban planning

Light pollution constitutes a major threat to biodiversity by decreasing habitat quality and landscape connectivity for nocturnal species. While there is an increasing consideration of biodiversity in urban management policies, the impact of artificial light is poorly accounted for. This is in a large part due to the lack of quantitative information and relevant guidelines to limit its negative effects. Here we compared the potential of two sources of information on light pollution, remote sensing (nocturnal picture taken from the International Space Station ISS) and ground-based (location of streetlights) data, to measure its impact on bats. Our aims were to (i) evaluate how light pollution affected Pipistrellus pipistrellus activity at the city scale, (ii) determine which source of information was the most relevant to measure light pollution's effect and (iii) define a reproducible methodology applicable in land management to account for biodiversity in lighting planning. We used citizen science data to model the activity of P. pipistrellus, a species considered light tolerant, within three cities of France while accounting for artificial light through a variable based on either source of information. We showed that at the city scale, P. pipistrellus activity is negatively impacted by light pollution irrespective of the light variable used. This detrimental effect was better described by variables based on ISS pictures than on streetlights location. Our methodology can be easily reproduced and used in urban planning to help take the impact of light pollution into consideration and promote a biodiversity-friendly management of artificial light.© 2018 Elsevier B.V.We thank the Association Nationale Recherche Technologie and Auddice Environnment for funding. We deeply thank all the volunteer of the Vigie-Nature for data collection and identification, especially Mathieu Abouladze, Yoann Allanic, Avana Andriamboavonjy, Michel Bonnavenc, Jean Burger, Alix Cosquer, Cecile Edelist, Caroline Fromont, Andreas Goli, Anne-Laure Gourmand, Anne Guezou, Clement Heroguel, Arzvael Jeusset, Robin Julien, Marine Legrand, Julie Marmet, Pierre mathieu, Shankar Meyer, Lara Millon, Jean Pierre Moussu, Julien Penvern, Emmanuelle Porcher, Marie Agnes Rabillard, Isabelle Schmidt, Assaf Shwartz, Celine Teplisky, Anne Tessedre, William Travers, Pauline Van Laere, Alan Vergnes. The field work in Lille was realized within the project TRAMENOIRE funded by the Region Nord Pas de Calais and the Fondation for Research on Biodiversity (FRB) and coordinated by Baptiste Faure and Alexandre Haquart. We deeply thank Alexis Laforge, Anaelle Bissonet and Vanille Thuillier for their help in data collection and identification in Lille.Peer Reviewe

Disentangling the Role of Cortico-Basal Ganglia Loops in Top–Down and Bottom–Up Visual Attention: An Investigation of Attention Deficits in Parkinson Disease

It is solidly established that top–down (goal-driven) and bottom–up (stimulus-driven) attention mechanisms depend on distributed cortical networks, including prefrontal and fronto-parietal regions. On the other hand, it is less clear whether the BG also contribute to one or the other of these mechanisms, or to both. The current study was principally undertaken to clarify this issue. Parkinson disease (PD), a neurodegen-erative disorder primarily affecting the BG, has proven to be an effective model for investigating the contribution of the BG to different brain functions; therefore, we set out to investigate deficits of top–down and bottom–up attention in a selected cohort of PD patients. With this objective in mind, we compared the performance on three computerized tasks of two groups of 12 parkinsonian patients (assessed without any treatment), one otherwise pharmacologically treated and the other also surgically treated, with that of a group of controls. The main behavioral tool for our study was an attentional capture task, which enabled us to tap the competition between top–down and bottom–up mechanisms of visual attention. This task was suitably combined with a choice RT and a simple RT task to isolate any specific deficit of attention from deficits in motor response selection and initiation. In the two groups of patients, we found an equivalent increase of attentional capture but also comparable delays in target selection in the absence of any salient distractor (reflecting impaired top–down mechanisms) and movement initiation compared with controls. In contrast, motor response selection processes appeared to be prolonged only in the operated patients. Our results confirm that the BG are involved in both motor and cognitive domains. Specifically, damage to the BG, as it occurs in PD, leads to a distinct deficit of top–down control of visual attention, and this can account, albeit indirectly, for the enhancement of atten-tional capture, reflecting weakened ability of top–down mechanisms to antagonize bottom–up control