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Biology subjects

Roussel, N.

Publications and source records attributed to Roussel, N..

3 recordsLinked to original sources

Alternative Lengthening of Telomeres and CINSARC are interconnected toward non-translocation-related sarcomas progression

Alternative lengthening of telomeres (ALT) is a telomere elongation mechanism activated during oncogenesis and primarily acting in tumors of mesenchymal origin. Although the proteins involved in the machinery enabling ALT to elongate telomeres are becoming better understood, the underlying biology of this mechanism remains unclear. In the present study, we took advantage of a fully characterized cohort of 98 leiomyosarcomas (LMS) from the French Sarcoma Group to further our understanding of the ALT mechanism. We first compared the transcriptomic profiles of ALT+ and TERT+ LMS and demonstrated a strong enrichment of the CINSARC signature in ALT+ tumors. The establishment of an ALT+-related signature in these LMS confirmed the close association between CINSARC and ALT in two additional cohorts of non-translocation-related sarcomas. In vitro mesenchymal models of spontaneous ALT induction showed increased CINSARC expression following acquisition of the ALT mechanism. Conversely, ALT inactivation, through BLM inhibition, led to decreased CINSARC expression. These results establish CINSARC as a new hallmark of the ALT mechanism in non-translocation-related sarcomas and demonstrate the association of a cellular biological process with the CINSARC prognostic signature, namely the ALT mechanism.

cancer biology↗

ClearScope: a fully integrated light sheet theta microscope for sub-cellular resolution imaging without lateral size constraints

Three-dimensional (3D) ex vivo imaging of cleared intact brains of animal models and large human and non-human primate postmortem brain specimens is important for understanding the physiological neural network connectivity patterns and the pathological alterations underlying neuropsychiatric and neurological disorders. Light-sheet microscopy has emerged as a highly effective imaging modality for rapid high-resolution imaging of large cleared samples. However, the orthogonal arrangements of illumination and detection optics in light sheet microscopy limits the size of specimen that can be imaged. Recently developed light sheet theta microscopy (LSTM) technology addressed this by utilizing a unique arrangement of two illumination light paths oblique to the detection light path, while allowing perpendicular arrangement of the detection light path relative to the specimen surface. Here, we report development of a next-generation, fully integrated, and user-friendly LSTM system for rapid sub-cellular resolution imaging uniformly throughout a large specimen without constraining the lateral (XY) size. In addition, we provide a seamlessly integrated workflow for image acquisition, data storage, pre- and post-processing, enhancement, and quantitative analysis. We demonstrate the system performance by high-resolution 3D imaging of intact mouse brains and human brain samples, and complete data analysis including digital neuron tracing, vessel reconstruction and design-based stereological analysis in 3D. This technically enhanced and user-friendly LSTM implementation will enable rapid quantitative mapping of molecular and cellular features of interests in diverse types of very large samples.

neuroscience↗

Age-related kinematic behavior on fast head-neck rotation target task in non-painful individuals aged from 8 to 85 years old

RationaleKinematic behavior during fast cervical rotations is a useful parameter for assessing sensorimotor control performances in neck-pain patients. However, in asymptomatic individuals from children to seniors, the influence of age still needs to be explored. Aim and methodWe assessed the impact of age on sensorimotor control performance of the head-neck with execution time and kinematic variables (time of task, mean speed/acceleration/deceleration, overshoots, minimum/maximum speed) during standardized fast rotation target task using the DidRen Laser test. Eighty volunteers were stratified in four different age-groups: Children [8-14y]: n=16; Young Adults [18-35y]: n=29; Old Adults [36-64y]: n=18; Seniors [65-85y]: n=17. ResultsTo perform the test, Children were slower compared to Young Adults (p<0.001) and Old Adults (p<0.001). It was also slower in Seniors compared to Young Adults (p<0.013). Mean speed was slower in Children and Seniors compared to Young Adults (p<0.001) and Old Adults (p<0.001). Mean acceleration was slower for Children compared to Young Adults (p<0.016) and Old Adults (p<0.015). Mean deceleration was slower for Children compared to Young Adults (p<0.001) and Old Adults (p<0.003). ConclusionThe DidRen Laser test allows us to discriminate age-specific performances for mean speed, acceleration and deceleration. Seniors and Children needed to be slower to become as precise as Young and Old people, no difference was observed for overshoots which assesses accuracy of movement. Age must therefore be considered as a key parameter when analyzing execution time and kinematic results during DidRen Laser test.

physiology↗