How to measure the relevance of a retargeting approach?

International audienceMost cell phones today can receive and display video content. Nonetheless, we are still significantly behind the point where premium made for mobile content is mainstream, largely available, and affordable. Significant issues must be overcome. The small screen size is one of them. Indeed, the direct transfer of conventional contents (not specifically shot for mobile devices) will provide a video in which the main characters or objects of interest may become indistinguishable from the rest of the scene. Therefore, it is required to retarget the content. Different solutions exist, either based on distortion of the image, on removal of redundant areas, or cropping. The most efficient ones are based on dynamic adaptation of the cropping window. They significantly improve the viewing experience by zooming in the regions of interest. Currently, there is no common agreement on how to compare different solutions. A retargeting metric is proposed in order to gauge its quality. Eye-tracking experiments, zooming effect through coverage ratio and temporal consistency are introduced and discussed

Control of the Unfolded Protein Response in Health and Disease

International audienceThe unfolded protein response (UPR) is an integrated, adaptive biochemical process that is inextricably linked with cell homeostasis and paramount to maintenance of normal physiological function. Prolonged accumulation of improperly folded proteins in the endoplasmic reticulum (ER) leads to stress. This is the driving stimulus behind the UPR. As such, prolonged ER stress can push the UPR past beneficial functions such as reduced protein production and increased folding and clearance to apoptotic signaling. The UPR is thus contributory to the commencement, maintenance, and exacerbation of a multitude of disease states, making it an attractive global target to tackle conditions sorely in need of novel therapeutic intervention. The accumulation of information of screening tools, readily available therapies, and potential pathways to drug development is the cornerstone of informed clinical research and clinical trial design. Here, we review the UPR's involvement in health and disease and, beyond providing an in-depth description of the molecules found to target the three UPR arms, we compile all the tools available to screen for and develop novel therapeutic agents that modulate the UPR with the scope of future disease intervention

L'étuve dans les châteaux et palais du Moyen Âge en France

The steam room in medieval french châteaux and palaces, by jean Mesqui. The private steam rooms in medieval châteaux and palaces constituted a luxury reserved for a minority of princes and great lords, essentially from the 1340 onwards. A synthesis concerning these little known installations is proposed on the basis of an inventory of preserved examples.Les chambres d'étuve privées dans les châteaux et palais du Moyen Age constituent un luxe réservé à une minorité de princes et de grands seigneurs, essentiellement à partir des années 1340. Un inventaire des exemplaires conservés à ce jour permet de proposer une synthèse de ces aménagements encore peu connus.Mesqui Jean, Amiot Christophe, Bon Philippe, Brodeur Jean, Carru Dominique, Chevet Pierre, Faucherre Nicolas, Marchant Sylvie. L'étuve dans les châteaux et palais du Moyen Âge en France. In: Bulletin Monumental, tome 159, n°1, année 2001. Les Bains privés au Moyen âge et à la Renaissance. pp. 7-20

NUPR1 interacts with eIF2α and is required for resolution of the ER stress response in pancreatic tissue

Nuclear protein 1 (NUPR1) is a stress response protein overexpressed upon cell injury in virtually all organs including the exocrine pancreas. Despite NUPR1\u27s well-established role in the response to cell stress, the molecular and structural machineries triggered by NUPR1 activation remain largely debated. In this study, we uncover a new role for NUPR1, participating in the unfolded protein response (UPR) and the integrated stress response. Biochemical results and ultrastructural morphological observations revealed alterations in the UPR of acinar cells of germline-deleted NUPR1 murine models, consistent with the inability to restore general protein synthesis after stress induction. Bioinformatic analysis of NUPR1-interacting partners showed significant enrichment in translation initiation factors, including eukaryotic initiation factor (eIF) 2α. Co-immunoprecipitation and proximity ligation assays confirmed the interaction between NUPR1 and eIF2α and its phosphorylated form (p-eIF2α). Furthermore, our data suggest loss of NUPR1 in cells results in maintained eIF2α phosphorylation and evaluation of nascent proteins by click chemistry revealed that NUPR1-depleted PANC-1 cells displayed a slower poststress protein synthesis recovery when compared to wild-type. Combined, these data propose a novel role for NUPR1 in the integrated stress response pathway, at least partially through promoting efficient PERK branch activity and resolution through a unique interaction with eIF2α

NUPR1 interacts with eIF2α and is required for resolution of the ER stress response in pancreatic tissue

International audienceNuclear protein 1 (NUPR1) is a stress response protein overexpressed upon cell injury in virtually all organs including the exocrine pancreas. Despite NUPR1’s well-established role in the response to cell stress, the molecular and structural machineries triggered by NUPR1 activation remain largely debated. In this study, we uncover a new role for NUPR1, participating in the unfolded protein response (UPR) and the integrated stress response. Biochemical results and ultrastructural morphological observations revealed alterations in the UPR of acinar cells of germline-deleted NUPR1 murine models, consistent with the inability to restore general protein synthesis after stress induction. Bioinformatic analysis of NUPR1-interacting partners showed significant enrichment in translation initiation factors, including eukaryotic initiation factor (eIF) 2α. Co-immunoprecipitation and proximity ligation assays confirmed the interaction between NUPR1 and eIF2α and its phosphorylated form (p-eIF2α). Furthermore, our data suggest loss of NUPR1 in cells results in maintained eIF2α phosphorylation and evaluation of nascent proteins by click chemistry revealed that NUPR1-depleted PANC-1 cells displayed a slower poststress protein synthesis recovery when compared to wild-type. Combined, these data propose a novel role for NUPR1 in the integrated stress response pathway, at least partially through promoting efficient PERK branch activity and resolution through a unique interaction with eIF2α

In situ quantification of diverse titanium dioxide nanoparticles unveils selective endoplasmic reticulum stress-dependent toxicity

Although titanium dioxide nanoparticles (TiO2 NPs) have been extensively studied, their possible impact on health due to their specific properties supported by their size and geometry, remains to be fully characterized to support risk assessment. To further document NPs biological effects, we investigated the impact of TiO2 NPs morphology on biological outcomes. To this end, TiO2 NPs were synthesized as nanoneedles (NNs), titanate scrolled nanosheets (TNs), gel-sol-based isotropic nanoparticles (INPs) and tested for perturbation of cellular homeostasis (cellular ion content, cell proliferation, stress pathways) in three cell types and compared to the P25. We showed that TiO2 NPs were internalized at various degrees and their toxicity depended on both titanium content and NPs shape, which impacted on intracellular calcium homeostasis thereby leading to endoplasmic reticulum stress. Finally, we showed that a minimal intracellular content of TiO2 NPs was mandatory to induce toxicity enlightening once more the crucial notion of internalized dose threshold beside the well-recognized dose of exposure.Mécanismes d'internalisation et de toxicité des nanoparticules d'oxyde de titane dans des organismes multicellulaires eucaryotesSupport of Public and Industrial Research using Ion Beam Technolog

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sous la direction d'I. de Lamberterie et J.-L. Lor

Comment la sûreté nucléaire et la radioprotection ont évolué après les accidents survenus en France et dans le monde.

Document sous copyright ASN en accès libre sur leur site internet : https://www.asn.fr/l-asn-informe/publications/les-cahiers-de-l-asn/les-cahiers-histoire-de-l-asn-n-1Les cahiers Histoire de l'ASNCe premier numéro des Cahiers Histoire de l’ASN est consacré au thème des « accidents nucléaires ». Si certains accidents nucléaires sont connus, au point d’ailleurs que leur nom propre est entré dans le langage courant, d’autres oscillent entre mémoire et oubli. C’est le cas pour deux accidents décrits dans ce numéro, ceux de Saint-Laurent-des-Eaux. Or, nous avons un devoir de construire une mémoire collective en capacité de servir pour demain.Trois idées clés nous semblent devoir être retenues à ce stade. D’abord, dans une société qui se veut sans risque, il est nécessaire de rappeler que le risque zéro n’existe pas et le nucléaire n’échappe pas à cette règle universelle. Comme le rappelle André-Claude Lacoste, président de l’ASN de 2006 à 2012, « personne ne peut garantir qu’il n’y aura jamais un accident grave en France. Il convient de faire deux choses : essayer de réduire la probabilité que cela arrive, ainsi que les conséquences, si cela arrive. C’est toute la philosophie de la sûreté nucléaire ».Ensuite, vis-à-vis des accidents du passé, il est nécessaire d’aller au-delà du caractère unique de ceux-ci pour en explorer les causes profondes et en tirer les enseignements qui permettront d’anticiper le potentiel accident, de le gérer au mieux, ainsi que la phase postaccidentelle. Nombre d’évolutions en matière organisationnelle ou de doctrine de sûreté nucléaire et de radioprotection proviennent de ce travail de retour d’expérience. Nous avons choisi de décrire ce travail au travers de cinq événements marquants, qui ont chacun généré des avancées majeures en matière de sûreté nucléaire et de radioprotection.Enfin, une des conséquences des accidents majeurs est bien l’émergence d’une conscience internationale des risques liés au nucléaire. Le message selon lequel la sûreté nucléaire est un bien commun et ne doit pas faire l’objet d’une compétition ou bien encore de manipulations géostratégiques, demeure, au regard des événements récents, plus que jamais d’actualité

A Novel Extrinsic Pathway for the Unfolded Protein Response in the Kidney

International audienceThe ribonuclease angiogenin is a component of the mammalian stress response, and functions in both cell-autonomous and non-cell-autonomous ways to promote tissue adaptation to injury. We recently showed that angiogenin regulates tissue homeostasis during AKI associated with endoplasmic reticulum (ER) stress through the production of transfer RNA fragments that interfere with translation initiation and thereby alleviate ER stress. However, whether the paracrine signaling mediated by angiogenin secretion is a genuine component of the ER stress response to kidney injury is unknown. Here, we explored the molecular mechanisms by which angiogenin is secreted upon ER stress, and determined how it modulates the inflammatory microenvironment. In cultured renal epithelial cells, ER stress specifically induced angiogenin secretion under the selective control of inositol-requiring enzyme 1α, a key activator of the unfolded protein response. The transcription factors spliced X-box-binding protein 1 and p65, which are activated by inositol-requiring enzyme 1α upon ER stress, each bound the angiogenin promoter and controlled the amount of angiogenin secreted. Furthermore, p65 promoted angiogenin transcription in an ER stress-dependent manner. Similar to secretion of the ER stress-induced proinflammatory cytokine IL-6, secretion of angiogenin required the ER-Golgi pathway. Notably, incubation of human macrophages with angiogenin promoted macrophage reprogramming toward an activated and proinflammatory phenotype. In patients, angiogenin expression increased upon renal inflammation, and the urinary concentration of angiogenin correlated with the extent of immune-mediated kidney injury. Collectively, our data identify angiogenin as a mediator of the ER stress-dependent inflammatory response and as a potential noninvasive biomarker of AK