Nucleocytoplasmic shuttling of the rabies virus P protein requires a nuclear localization signal and a CRM1-dependent nuclear export signal

AbstractRabies virus P protein is a co-factor of the viral RNA polymerase. It has been shown previously that P mRNA directs the synthesis of four N-terminally truncated P products P2, P3, P4, and P5 due to translational initiation by a leaky scanning mechanism at internal Met codons. Whereas P and P2 are located in the cytoplasm, P3, P4, and P5 are found in the nucleus. Here, we have analyzed the molecular basis of the subcellular localization of these proteins. Using deletion mutants fused to GFP protein, we show the presence of a nuclear localization signal (NLS) in the C-terminal part of P (172–297). This domain contains a short lysine-rich stretch (211KKYK214) located in close proximity with arginine 260 as revealed by the crystal structure of P. We demonstrate the critical role of lysine 214 and arginine 260 in NLS activity. In the presence of Leptomycin B, P is retained in the nucleus indicating that it contains a CRM1-dependent nuclear export signal (NES). The subcellular distribution of P deletion mutants indicates that the domain responsible for export is the amino-terminal part of the protein. The use of fusion proteins that have amino terminal fragments of P fused to β-galactosidase containing the NLS of SV40 T antigen allows us to identify a NES between residues 49 and 58. The localization of NLS and NES determines the cellular distribution of the P gene products

Federated learning enables big data for rare cancer boundary detection.

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

Author Correction: Federated learning enables big data for rare cancer boundary detection.

10.1038/s41467-023-36188-7NATURE COMMUNICATIONS14

Federated Learning Enables Big Data for Rare Cancer Boundary Detection

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

La trajectoire de vie d'une femme ayant projeté et vécu la parentalité seule saisie selon une méthode descriptive

Ce mémoire a pour objet la lecture d'une trajectoire de vie de femme ayant projeté et vécu la parentalité seule. La problématique est étayée selon diverses perspectives scientifiques qui examinent le vécu de chefs de familles monoparentales, qui sont le plus souvent des femmes célibataires, veuves ou séparées, afin par la suite de saisir, selon un alliage de ces perspectives qui se veut qualitatif, l'expérience de vie résultant de l'acte volontaire d'être le seul parent d'un enfant. Une méthode descriptive de lecture de données a été développée afin de dépeindre le détail de la vie d'une femme ayant pour plus de dix ans vécu ce choix de vie. Cette méthode vise plus spécifiquement à isoler les données portant sur l'expérience vocationnelle

La trajectoire de vie d'une femme ayant projeté et vécu la parentalité seule saisie selon une méthode descriptive

Ce mémoire a pour objet la lecture d'une trajectoire de vie de femme ayant projeté et vécu la parentalité seule. La problématique est étayée selon diverses perspectives scientifiques qui examinent le vécu de chefs de familles monoparentales, qui sont le plus souvent des femmes célibataires, veuves ou séparées, afin par la suite de saisir, selon un alliage de ces perspectives qui se veut qualitatif, l'expérience de vie résultant de l'acte volontaire d'être le seul parent d'un enfant. Une méthode descriptive de lecture de données a été développée afin de dépeindre le détail de la vie d'une femme ayant pour plus de dix ans vécu ce choix de vie. Cette méthode vise plus spécifiquement à isoler les données portant sur l'expérience vocationnelle

Les protéines issues du gène de la phosphoprotéine rabique (étude du trafic intracellulaire et identification de partenaires cellulaires)

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Le nouveau visage de l'expertise de gestion à la lumière de l'expérience anglaise

The 1984 reform of French company law has given investigations into companies a new look by enlarging the right to apply to applicants other than shareholders, such as the Commission des operations de bourse, the « ministère public » (public prosecutor) and worker's committees. Did it change its nature too ? Comparison with English Law has a great interest : its experience of such an intervention into the affairs of a company by a public authority (that is to say the secretary of state for trade) helps to understand better the new role of the COB and the « ministère public ». On the light of this comparison, it appears that in France these investigations remain conditionned by the interest of the company and, despite what the reform seemed to imply, are still a means of information as well as control for the benefit main of the shareholders.La loi du 1er mars 1984 a donné un nouveau visage à l'expertise de gestion en étendant la qualité de demandeur, auparavant réservée aux actionnaires, au comité d'entreprise, au ministère public et à la Commission des opérations de bourse. En a-t-elle changé aussi la nature ? Le rapprochement avec le droit anglais présente un grand intérêt pour mieux appréhender ces nouvelles attributions de la COB et du ministère public, car l'autorité publique (en l'occurrence le ministère du Commerce) joue depuis longtemps un rôle essentiel dans ce domaine. A la lueur de cette comparaison, il apparaît que l'expertise de gestion reste conditionnée par l'intérêt de la société et qu'elle est une mesure non seulement d'information mais aussi de contrôle dont les principaux bénéficiaires sont, malgré les apparences de la réforme, toujours les actionnaires.Poisson Schodermeier Marie-Danielle. Le nouveau visage de l'expertise de gestion à la lumière de l'expérience anglaise. In: Revue internationale de droit comparé. Vol. 39 N°4, Octobre-décembre 1987. pp. 913-944

A functional magnetic resonance imaging study of pathophysiological changes responsible for mirror movements in Parkinson's disease.

Mirror movements correspond to involuntary movements observed in the limb contralateral to the one performing voluntary movement. They can be observed in Parkinson's disease (PD) but their pathophysiology remains unclear. The present study aims at identifying their neural correlates in PD using functional magnetic resonance imaging. Ten control subjects and 14-off drug patients with asymmetrical right-sided PD were included (8 with left-sided mirror movements during right-hand movements, and 6 without mirror movements). Between-group comparisons of BOLD signal were performed during right-hand movements and at rest (p<0.005 uncorrected). The comparison between PD patients with and without mirror movements showed that mirror movements were associated with an overactivation of the insula, precuneus/posterior cingulate cortex bilaterally and of the left inferior frontal cortex and with a deactivation of the right dorsolateral prefrontal cortex, medial prefrontal cortex, and pre-supplementary motor area and occipital cortex. These data suggest that mirror movements in Parkinson's disease are promoted by: 1- a deactivation of the non-mirroring inhibitory network (dorsolateral prefrontal cortex, pre-supplementary motor area); 2- an overactivation of prokinetic areas (notably the insula). The concomitant overactivation of a proactive inhibitory network (including the posterior cingulate cortex and precuneus) could reflect a compensatory inhibition of mirror movements

BOLD signal changes related to Mirror Movements.

<p><b>A:</b> Reduction of activation during MM (PD+MM B: Increase of activation during MM (PD+MM >PD-MM). Graphs show the regionally averaged beta weights across patients from each group. Error bars indicate inter-patient standard error of the mean (SEM). L = left; R = right.</p