Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations

Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. Conclusion: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors.Peer reviewe

Aquatic-terrestrial transitions of feeding systems in vertebrates : a mechanical perspective

Transitions to terrestrial environments confront ancestrally aquatic animals with several mechanical and physiological problems owing to the different physical properties of water and air. As aquatic feeders generally make use of flows of water relative to the head to capture, transport and swallow food, it follows that morphological and behavioral changes were inevitably needed for the aquatic animals to successfully perform these functions on land. Here, we summarize the mechanical requirements of successful aquatic-to-terrestrial transitions in food capture, transport and swallowing by vertebrates and review how different taxa managed to fulfill these requirements. Amphibious ray-finned fishes show a variety of strategies to stably lift the anterior trunk, as well as to grab ground-based food with their jaws. However, they still need to return to the water for the intra-oral transport and swallowing process. Using the same mechanical perspective, the potential capabilities of some of the earliest tetrapods to perform terrestrial feeding are evaluated. Within tetrapods, the appearance of a mobile neck and a muscular and movable tongue can safely be regarded as key factors in the colonization of land away from amphibious habitats. Comparative studies on taxa including salamanders, which change from aquatic feeders as larvae to terrestrial feeders as adults, illustrate remodeling patterns in the hyobranchial system that can be linked to its drastic change in function during feeding. Yet, the precise evolutionary history in form and function of the hyolingual system leading to the origin(s) of a muscular and adhesive tongue remains unknown

Stratégie de restauration de la fonction diaphragmatique après lésion traumatique de la moelle épinière cervicale haute

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

Dynamic modelling for a twin screw food extruder: Analysis of the dynamic behaviour through process variables

International audienceFood extrusion processes are multiple input, multiple output complex systems. In this paper, the extrusion cooker is simplified into a single input, single output dynamic system, even though multi-input tests have also been performed. Its dynamic characteristics are obtained with step tests on different operating variables: feed rate, moisture content and screw speed. The response is monitored on the following outputs: melt pressure, melt temperature and specific mechanical energy.The results show the following: — the behaviour of the extruder generally verifies the conditions of the BIBO (Bounded Input, Bounded Output) stability, — the process can be considered to be stationary and non-linear. The non-linearity of the system is highlighted by: — the variability of the steady state grain as a function of step magnitude, — the lack of superimposition of the gains when performing multi-input tests.The study of the transient behaviour shows that the systems exhibit a non-separable non-linearity. The observed dynamic characteristics are rising problems that must be taken into account in designing control systems for food extrusion