Combining intracellular selection with protein-fragment complementation to derive A interacting peptides

Aggregation of the β-amyloid (Aβ) peptide into toxic oligomers is considered the primary event in the pathogenesis of Alzheimer's disease. Previously generated peptides and mimetics designed to bind to amyloid fibrils have encountered problems in solubility, protease susceptibility and the population of small soluble toxic oligomers oligomers. We present a new method that opens the possibility of deriving new amyloid inhibitors. The intracellular protein-fragment complementation assay (PCA) approach uses a semi-rational design approach to generate peptides capable of binding to Aβ. Peptide libraries are based on Aβ regions responsible for instigating amyloidosis, with screening and selection occurring entirely inside Escherichia coli. Successfully selected peptides must therefore bind Aβ and recombine an essential enzyme while permitting bacterial cell survival. No assumptions are made regarding the mechanism of action for selected binders. Biophysical characterisation demonstrates that binding induces a noticeable reduction in amyloid. Therefore, this amyloid-PCA approach may offer a new pathway for the design of effective inhibitors against the formation of amyloid in general

Bury me, my love: (non)choosing reading paths

This contribution falls within the domain of children’s and young adults’ digital literature and, in particular, in that segment of the field aimed at exploring both the potential and the limits of reading digital literary works at school. In order to describe the actual reception process (and eventually to accompany the formal introduction of e-lit creations in the French literature school programs), a selection of literary apps was presented to eight groups of young readers, across different school levels: two adaptations of contemporary picturebooks were read in four primary school classes (I can’t wait [France Télévision, 2013] and With a few bricks [Dieudonne, 2014]), while an interactive literary narrative experience (Loss of grasp [Bouchardon, 2016]) and a scrolling graphic novel (Phallaina [France Télévision, 2016]) were respectively analyzed in two middle and high-schools groups. If those experiences lead to describe how young readers handle the narrative interface and manage to combine the multimodal materials composing the message to build their comprehension, they couldn’t clarify how non-linear reading paths and discontinuous narrative flows may be perceived and analyzed in a school reading situation. We thus involved a sample of 32 high-school students in the reading of Bury me, me love [Plug In Digital, 2017], a non-linear fictional creation(inspired from a true story) partially determined by the literary device, that offers different issues according to the readers’ choices.Defined as a game of reality , the story follows the vicissitudes of Nour, a young Syrian woman who tries to flee her country, and appears as a conversation via a messaging app between the protagonist and his companion, who is embodied by the reader him/herself. By following the flow of the exchanges, the story progresses, and the journey of the protagonist is at the same established and addressed towards one of its 19 possible endings. The time of the narration also depends on the reader, who can either respect the rhythm of the conversation, intended to reproduce the actual chronology of the journey, or accelerate the narration in order to read the sequence of sms in a continuous flow. In both cases, each choice is irreversible and has unexpected consequences on the narrative. A double discontinuity in the reading is thus installed: one concerns the narrative, whose deployment may abruptly deviate from its most likely issue; the other concerns the reading itself, quickly but systematically interrupted by the necessity of selecting a crucial preference among a limited set of options. In this context, it is worth observing if the role of the device, the programmed choices and the discontinuity of the narrative plot are effectively considered as part of the literary construction. In order to answers to those questions, we will analyze the verbal exchanges held by the students during thethree-week reading sessions, the reading diaries written during the experience and the 50 answers they submitted in the final questionnaire. The interpretation of the data will lay out different positions and, globally, a certain resistance at accepting a renewed reading role. Literary apps With a few bricks,Dieudonne, 2014. Loss of grasp, Bouchardon, 2016. I can’t wait, France Télévision, 2013. Phallaina, France Télévision, 2016. Bury me, me love, Plug In Digital, 2017

No more time to stay ‘single’ in the detection of Anisakis pegreffii, A. simplex (s. s.) and hybridization events between them: a multi-marker nuclear genotyping approach

A multi-marker nuclear genotyping approach was performed on larval and adult specimens of Anisakis spp. (N = 689) collected from fish and cetaceans in allopatric and sympatric areas of the two species Anisakis pegreffii and Anisakis simplex (s. s.), in order to: (1) identify specimens belonging to the parental taxa by using nuclear markers (allozymes loci) and sequence analysis of a new diagnostic nuclear DNA locus (i.e. partial sequence of the EF1 α−1 nDNA region) and (2) recognize hybrid categories. According to the Bayesian clustering algorithms, based on those markers, most of the individuals (N = 678) were identified as the parental species [i.e. A. pegreffii or A. simplex (s. s.)], whereas a smaller portion (N = 11) were recognized as F1 hybrids. Discordant results were obtained when using the polymerase chain reaction–restriction fragment length polymorphisms (PCR–RFLPs) of the internal transcribed spacer (ITS) ribosomal DNA (rDNA) on the same specimens, which indicated the occurrence of a large number of ‘hybrids’ both in sympatry and allopatry. These findings raise the question of possible misidentification of specimens belonging to the two parental Anisakis and their hybrid categories derived from the application of that single marker (i.e. PCR–RFLPs analysis of the ITS of rDNA). Finally, Bayesian clustering, using allozymes and EF1 α−1 nDNA markers, has demonstrated that hybridization between A. pegreffii and A. simplex (s. s.) is a contemporary phenomenon in sympatric areas, while no introgressive hybridization takes place between the two species

Stroke, complex regional pain syndrome and phantom limb pain: Can commonalities direct future management?

Despite being different conditions, complex regional pain syndrome type 1, phantom limb pain and stroke share some potentially important similarities. This report examines experimental and clinical findings from each patient population. It identifies common aspects of symptomatic presentation, sensory phenomena and patterns of cortical reorganization. Based on these common findings, we argue that established principles of stroke rehabilitation are also applicable to rehabilitation of complex regional pain syndrome type 1 and phantom limb pain. In addition, we contend that promising treatment approaches for complex regional pain syndrome type I and phantom limb pain may be helpful in stroke rehabilitation. Examples of emerging supportive evidence for these hypotheses are provided and discussed

Des rafles de Boscawen au « Vengeur du Peuple »

La bataille navale est, par nature, un acte de guerre violent se déroulant dans l’espace maritime lui-même hostile à l’homme. Les évolutions perceptibles dans cet art de la guerre, du XVIIe siècle à la fin du Premier Empire, s’accompagnent d’indices prouvant l’agressivité croissante des combats. Cette violence accrue précède nettement les guerres révolutionnaires et impériales qui la porteront à son paroxysme. Elle apparaît au milieu du XVIIIe siècle, avec en particulier les combats de la guerre de Sept Ans.Auparavant, outil de prestige à la pointe de la technologie navale, le vaisseau de guerre est la cible de l’ennemi qui cherche à le prendre pour l’exhiber comme symbole de sa domination maritime. Avec le basculement de la guerre de Sept Ans, apparaît la destruction comme langage de puissance ciblant l’outil avant de viser les hommes, potentiel naval d’une nation. La panoplie des moyens s’élargit alors pour anéantir l’autre. L’enfermement concentrationnaire et funeste sur les pontons, la mise au point d’armes létales, l’utilisation de techniques de combat meurtrières, laissent peu de chance aux hommes d’échapper à l’acharnement et annoncent la fin des principes d’humanité.A naval battle is, by nature, a violent act of war taking place in the maritime space—itself hostile to man. Perceptible evolutions in this art of war, from the 17th century to the end of the First French Empire, were accompanied by various signs proving the growing aggressiveness of fights. This increased violence began far before the revolutionary and imperial wars—days when violence was at its height. It appeared in the mid-17th century, in particular with the fights of the Seven Years’ War. Before, a warship—a prestige tool in the forefront of naval technology—was the target of the enemy, so as to be potentially displayed as a symbol of maritime domination. With the shift of the Seven Years’ War, destruction became a language of power targetting the tool before aiming at the men (the naval potential of a nation). The range of the possible means of how to wipe the other out then got wider. The harmful confinement on the hulk, the perfecting of lethal weapons, the recourse to deadly fighting techniques, gave men little chance to escape such fierceness, and foreshadowed the end of humane principles

Helicorder digitale

Helicorder digital

Safety roads: the analysis of driving behaviour and the effects on the infrastructural design

Road design should ensure the correct behaviour of drivers in terms of speed and level of attention. Nevertheless, in some cases users are not able to visualize the carriageway enough correctly, owing to the misled road layout or the loss of visibility. In this research, road safety management was assessed with the driving and visual behaviour of users, considering the impact of different configurations of pedestrian crossings and road signs in order to reduce accidents. Even if users focus their attention on the zebra crossing (60%) and the vertical sign (24%), 16% of them have had no perception of the pedestrian crossings. This result shows how pedestrian crossings represent critical points that could compromise the safety of vulnerable users also in relation to speed. In fact, driving behaviour highlights 50 km/h of the average speed at 100 meters before the crosswalk, which allows having a too short time to stop the vehicle in safety. Moreover, the maximum speed underlines that users drive beyond the limit imposed by the road’s rules. It is thus necessary to require the implementation of road infrastructure so as to modify the driving behaviour. Starting from the Road Safety Review, it was then possible to detect the critical issues and correlate a visual and kinematic analysis so as to intervene accurately

Zones construites, zones désertes sur le littoral atlantique. Les leçons du passé

Cet article explore la question des relations entre les installations en zone littorale, la mémoire locale et les connaissances officielles sur l’environnement littoral. Sous l’angle historique, cette étude peut débuter sous le règne de Louis XIV. Les archives officielles témoignent de l’intérêt de Colbert pour la mémoire locale dans le processus de décision de l’installation du port et arsenal de Rochefort. La Révolution Française a modifié ce mode de décision et la Monarchie Libérale (1830-1848) en a fondé un autre. Ainsi, les autorités ont laissé les communautés littorales libres d’aménager des marais et des polders par elles mêmes, en intervenant le moins possible. Le siècle suivant (1850-1950) a connu un accroissement du contrôle administratif. La mémoire locale a été collectée et connectée aux progrès scientifiques afin de donner naissance à une doctrine officielle de développement littoral. La croissance du tourisme a définitivement brisé ce modèle, en substituant une société urbaine et sans racines aux modes de vie traditionnels et anciens, réglés par la mémoire locale. Au même moment, les technologies numériques ont établi un monopole sur la formation des ingénieurs. Cela a contribué à faire avancer la connaissance des littoraux mais cela a aussi accéléré la perte de la mémoire locale, particulièrement celle des risques côtiers.This article explores the question of relationships between coastal settlements, inhabitants memory and official knowledges about littoral environment. From an historical point of view, the study begins during the reign of Louis 14. The official archives show that Colbert was interested in collecting people’s experience so as to decide where and how would be created the new harbour and arsenal of Rochefort by the monarchy. Such decision process has been changed by the French Revolution and a new one was built during the Liberal Monarchy (1830-1848). Therefore, the authorities let the littoral communities free to make up polders and marshes, with few interventions. The following century (1850-1950) has been a time for an increasing adminitrative control. The strong local experience has been collected and connected to the science’s progress so as to create an official doctrine of coastal development. The take-off of the tourism has definitly broken this model, replacing the old and traditionnal way of life – ruled by the local memory – by an urban and rootless society. At the same time, the monopoly of numeric technologies on ingeneer’s sciences has become a reality. Althought it seems to be a good way to fill some gap of knowledges, it has also accelerated the loss of experience and local memory, specialy about maritime risks