Dialogue entre les voies de signalisation de l’insuline et de la sérotonine dans le cerveau : Implication de la voie PI3K/Akt et conséquences comportementales dans des modèles d’insulino-résistance

Insulin and serotonin (5-HT) are two key players in the maintenance of energy homeostasis which is controlled by the hypothalamus. In this brain region, insulin mediates numerous metabolic effects via the activation of the PI3K/Akt signaling pathway. 5-HT exerts similar biological properties by acting in the hypothalamus but the signaling pathways accountable for these effects are still unclear. Moreover, it has been reported that 5-HT induces the activation of the PI3K/Akt pathway in the hippocampus and the inhibition of GSK3β, suggesting this action as a potential mechanism for the antidepressant effects of this neurotransmitter.The main objectives of this thesis were to study 1/ the serotonin-induced activation of the PI3K/Akt in the hypothalamus of wild type and diabetic rats (Goto-Kakizaki model) and search a potential cross-talk with insulin and, 2/ the mechanisms underlying the high-fat diet induced depression by investigating the role of the phosphorylation of Akt and GSK3β by 5-HT, insulin and leptin in the hippocampus of rats.Here, we show that 5-HT triggers the PI3K/Akt signaling pathway in the rat hypothalamus, and that this activation is attenuated in insulin-resistant conditions, suggesting a cross-talk between insulin and 5-HT. Moreover, we reported that high-fat diet feeding induces a reversible depressive-like behavior, which may involve the PI3K/Akt/GSK3β pathway in subgranular neurons of the dentate gyrus. In conclusion, the activation of the PI3K/Akt pathway and its target GSK3β by 5-HT in the hypothalamus and in the dentate gyrus, respectively, can be impaired in insulin-/leptin-resistant states, which may underlie a link between metabolic diseases and depression.L’insuline et la sérotonine (5-HT) sont deux acteurs majeurs du maintien de l’homéostasie énergétique, fonction placée sous le contrôle de l’hypothalamus. En ciblant cette région, l’insuline remplit de nombreuses fonctions métaboliques via l’activation de la voie PI3K/Akt. La 5-HT exercent des effets biologiques similaires mais les voies de signalisation impliquées dans ces processus étaient jusqu’alors mal connues. De plus, il avait été démontré que la 5-HT est capable d’activer la voie PI3K/Akt/GSK3β dans l’hippocampe, mécanisme sous-tendant potentiellement les effets antidépresseurs du neurotransmetteur. Les principaux objectifs de cette thèse étaient d’étudier 1/ l’activation de la voie PI3K/Akt par la 5-HT dans l’hypothalamus de rats diabétiques (modèle Goto-Kakizaki) et chercher un potentiel dialogue avec l’insuline and 2/ les mécanismes sous-tendant l’induction de la dépression par une alimentation hyperlipidique, par l’analyse de la phosphorylation d’Akt et GSK3β sous l’action de l’insuline, de la leptine et de la 5-HT dans l’hippocampe de rat.Ici on montre que 1/ la 5-HT stimule la voie PI3K/Akt dans l’hypothalamus et que la phosphorylation d’Akt induite par la 5-HT est atténuée dans des conditions d’insulino-résistance, suggérant l’existence d’un dialogue entre les voies de signalisation de l’insuline et de la 5-HT. Par ailleurs, nos résultats indiquent qu’une alimentation hyperlipidique induit un comportement dépressif réversible chez le rat, qui pourrait impliquer la voie PI3K/Akt/GSK3β dans les neurones subgranulaires du gyrus denté. La mise en évidence d’un dialogue entre les voies de signalisation de la 5-HT, de la leptine et de l’insuline au niveau central enrichit nos connaissances sur le rôle de ces facteurs dans la régulation de l’homéostasie énergétique et de l’humeur, et propose un lien moléculaire entre diabète de type 2, obésité et dépressio

A methodology for the assessment of the proliferation resistance of nuclear power systems: topical report

A methodology for the assessment of the differ- ential resistance of various nuclear power systems to misuse for the production of nuclear weapons is developed. In the context of this study, a nuclear system comprises a particular fuel cycle and the political/institutional framework in which it oper- ates. The latter may be country-specific. The methodology is based on the principles of Multiattribute Decision Analysis, wherein a set of in- dices or attributes which characterize the prolifera- tion resistance of nuclear systems is defined and evaluated for particular systems. Emphasis has been placed on delineating the logical structure of the problem, rather than on rank ordering the various systems of interest via techniques which aggregate the attribute values in a consistent manner. However, examples of the application of decision analysis in the latter situation have also been given to illustrate the potential of this approach to the proliferation problem

Revisiting the effect of income on health in Europe : evidence from the 8th round of the European social survey

First published online: February 2020This study provides new evidence about the effects of income on population health. To do so, our first research question controls for the absolute income hypothesis : Has the recent deterioration of individual income had as a result a lower health status in population across European countries? : We assume, as the bulk of the associated studies have found, that the lower the income of an individual, the lower his/her health status. Our second research objective is to examine the validity of the relative income hypothesis. To shed light on this issue, we test two different questions : What is the relationship between an individual's health status and a country's wealth and how self-rated health is associated with the degree of income inequality in a society? : We expect that the population in wealthier countries report higher health status and individuals who live in countries with higher income inequalities report lower health status. By employing a multilevel binomial model and treating data from the latest European Social Survey Round 8 (2016/2017) from 23 countries in Europe, we have found strong evidence in favor of the above-mentioned hypotheses

The Radion in the Karch-Randall Braneworld

In a braneworld context, the radion is a massless mode coupling to the trace of the matter stress tensor. Since the radion also governs the separation between branes, it is expected to decouple from the physical spectrum in single brane scenarios, such as the one-brane Randall-Sundrum model. However, contrary to expectations, we demonstrate that the Karch-Randall radion always remains as a physical excitation, even in the single brane case. Here, the radion measures the distance not between branes, but rather between the brane and the anti-de Sitter boundary on the other side of the bulk.Comment: 19 pages, Plain Te

Correction: Mutations in LRRK2 linked to Parkinson disease sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microglia

[This corrects the article DOI: 10.1371/journal.pbio.3001480.]

An authoring tool for educators to make virtual labs

This paper focuses on the design and implementation of a tool that allows educators to author 3D virtual labs. The methodology followed is based on web 3D frameworks such as three.js and WordPress that allowed us to develop simplified interfaces for modifying Unity3D templates. Two types of templates namely one for Chemistry and one for Wind Energy labs were developed that allow to test the generalization, user-friendliness and usefulness of such an approach. Results have shown that educators are much interested on the general concept, but several improvements should be made towards the user-friendliness and the intuitiveness of the interfaces in order to allow the inexperienced educators in 3D gaming to make such an attempt.peer-reviewe

AEDGE: Atomic Experiment for Dark Matter and Gravity Exploration in Space

Abstract: We propose in this White Paper a concept for a space experiment using cold atoms to search for ultra-light dark matter, and to detect gravitational waves in the frequency range between the most sensitive ranges of LISA and the terrestrial LIGO/Virgo/KAGRA/INDIGO experiments. This interdisciplinary experiment, called Atomic Experiment for Dark Matter and Gravity Exploration (AEDGE), will also complement other planned searches for dark matter, and exploit synergies with other gravitational wave detectors. We give examples of the extended range of sensitivity to ultra-light dark matter offered by AEDGE, and how its gravitational-wave measurements could explore the assembly of super-massive black holes, first-order phase transitions in the early universe and cosmic strings. AEDGE will be based upon technologies now being developed for terrestrial experiments using cold atoms, and will benefit from the space experience obtained with, e.g., LISA and cold atom experiments in microgravity. KCL-PH-TH/2019-65, CERN-TH-2019-12

The role of photodynamic cystoscopy in diagnosis of urinary bladder cancer and follow up of patients with non muscle invasive bladder cancer who have undergone adjuvant therapy with intravesical instillations

Objective: This study evaluated the efficacy of hexaminolevulinate fluorescence cystoscopy as a diagnostic tool for bladder cancer and as a tool for the follow up in patients with non-invasive bladder cancer. The study was performed in the Department of Urology in Hippokratio General Hospital of Athens between October 2008 and May 2012. Material and Methods: Fifty patients (43 males and 7 females) who were investigated for hematuria were included in the study. White light cystoscopy (WLC) was first performed in all patients and after was performed a fluorescence cystoscopy (BLC-blue light cystoscopy). Biopsies were collected from any suspiciousarea and resection of the tumors identified (TUR). Three and twelve months after the first TUR a second BLC and WLC were performed and if there was recurrence we performed a TUR. Results: Patients demographic data and clinical history are presented. Two-hundred twenty specimens were extracted and bladder cancer was diagnosed in 137. There were 17 CIS lesions all diagnosed with BLC whereas only 11 with WLC. WLC correctly diagnosed 109/140 specimens and the positive and negative predictive values were 77, 9% and 65% respectively. The sensitivity and specificity were 79, 6% and 62, 6% respectively. BLC diagnosed 125/169 specimens and the positive and negative predictive values were 73, 9% and 76,5% respectively. The sensitivity of BLC was 91, 2% and the specificity 46, 9%. In 3 months follow up, 126 specimens were extracted where Ca was found in 68 and no cancer in 58 (22 were normal tissue and 36 were chronic inflammation). From these specimens 38 were positive for cancer with BCL (false positive) vs. 28 false positive with WLC. There were 4 CIS. All CIS were detected with BLC and ¾ with WLC.In twelve months 98 specimens were extracted where 56 of them were cancer and 42 no cancer. The False positive with BLC were 16 and with WLC 13. Seven patients had cancer recurrence and two of them had invasive bladder cancer. Conclusion: BLC is a valuable diagnostic method for the diagnosis of non-muscle invasive bladder cancer(NMIBC) and especially for CIS. False positive biopsies with BLC after intravescical treatment is similar to those with WLC. BLC seems to be a method for the improvement of management in patients with NMIBCΣκοπός: Αυτή η μελέτη εκτίμησε την αποτελεσματικότητα της BLC στη διάγνωση και στην παρακολούθηση ασθενών με μη διηθητικό καρκίνο της ουροδόχουκύστεως. Η μελέτη έγινε στην Ουρολογική Κλινική στο Ιπποκράτειο Νοσοκομείο Αθήνας από τον Οκτώβριο του 2008 έως το Μάιο του 2012.Υλικό και Μέθοδος: Πενήντα ασθενείς (43 άνδρες και 7 γυναίκες) που υποβλήθηκαν σε έλεγχο για αιματουρία περιλήφθηκαν στη μελέτη. Η WLC πραγματοποιήθηκε αρχικά σε όλους τους ασθενείς και μετά έγινε σε όλους BLC. Λήφθηκαν βιοψίες από όλες τις ύποπτες περιοχές και σε περίπτωση όγκων γινόταν διουρηθρική εκτομή (TURBT). Τρεις και δώδεκα μήνες μετά την πρώτη TURBT οι ασθενείς υποβλήθηκαν και πάλι στον ίδιο έλεγχο και σε παρουσία όγκων έγινε ξανά διουρηθρική εκτομή .Αποτελέσματα:Λήφθηκαν 220 δείγματα όπου διαγνώστηκε καρκίνος στα 137. Υπήρχαν 17 καρκίνο ιinsitu που διαγνώστηκαν με BLC ενώ η WLC διέγνωσε τους 11. Με τη WLC διαγνώστηκαν σωστά 109/140 δείγματα και οι θετική και αρνητική προγνωστική αξία ήταν αντίστοιχα 77, 9% και 65%. Ευαισθησία και η ειδικότητα ήταν 79, 6% και 62, 6% αντίστοιχα. Με την BLC διαγνώστηκαν 125/169 δείγματα και η θετική και αρνητική προγνωστική αξία ήταν 73, 9% και 76,5% αντίστοιχα. Η ευαισθησία της BLC ήταν 91,2% και η ειδικότητα 46,9%. Στους 3 μήνες, λήφθηκαν 126 δείγματα όπου βρέθηκε καρκίνος στα 68. Σε 58 δείγματα δεν ανευρέθηκε καρκίνος. Από αυτά 22 ήταν φυσιολογικός ιστός και 36 χρόνια φλεγμονή. Βρέθηκαν 38 ψευδώςθετικά με την BLC και 28 με την WLC. Υπήρχαν 4 CIS που εντοπίστηκαν με BLC και ¾ εντοπίστηκαν με WLC. Στους 12 μήνες λήφθηκαν 98 δείγματα όπου 56 ήταν καρκίνος και 42 δεν έδειξαν καρκίνο. Τα ψευδώς θετικά με την BLC ήταν 16 ενώ με τη WLC 13. Επτά ασθενείς είχαν υποτροπή στους 12 μήνες και 2 από αυτούς ανέπτυξαν διηθητικό καρκίνο.Συμπέρασμα: Η BLC είναι μια σημαντική διαγνωστική μέθοδος για τη διάγνωση και την παρακολούθηση ασθενών με μη διηθητικό καρκίνο της ουροδόχου κύστεως και ειδικά με CIS

Dialogue entre les voies de signalisation de l insuline et de la sérotonine dans le cerveau (Implication de la voie PI3K/Akt et conséquences comportementales dans des modèles d insulino-résistance)

L insuline et la sérotonine (5-HT) sont deux acteurs majeurs du maintien de l homéostasie énergétique, fonction placée sous le contrôle de l hypothalamus. En ciblant cette région, l insuline remplit de nombreuses fonctions métaboliques via l activation de la voie PI3K/Akt. La 5-HT exercent des effets biologiques similaires mais les voies de signalisation impliquées dans ces processus étaient jusqu alors mal connues. De plus, il avait été démontré que la 5-HT est capable d activer la voie PI3K/Akt/GSK3b dans l hippocampe, mécanisme sous-tendant potentiellement les effets antidépresseurs du neurotransmetteur. Les principaux objectifs de cette thèse étaient d étudier 1/ l activation de la voie PI3K/Akt par la 5-HT dans l hypothalamus de rats diabétiques (modèle Goto-Kakizaki) et chercher un potentiel dialogue avec l insuline and 2/ les mécanismes sous-tendant l induction de la dépression par une alimentation hyperlipidique, par l analyse de la phosphorylation d Akt et GSK3b sous l action de l insuline, de la leptine et de la 5-HT dans l hippocampe de rat.Ici on montre que 1/ la 5-HT stimule la voie PI3K/Akt dans l hypothalamus et que la phosphorylation d Akt induite par la 5-HT est atténuée dans des conditions d insulino-résistance, suggérant l existence d un dialogue entre les voies de signalisation de l insuline et de la 5-HT. Par ailleurs, nos résultats indiquent qu une alimentation hyperlipidique induit un comportement dépressif réversible chez le rat, qui pourrait impliquer la voie PI3K/Akt/GSK3b dans les neurones subgranulaires du gyrus denté. La mise en évidence d un dialogue entre les voies de signalisation de la 5-HT, de la leptine et de l insuline au niveau central enrichit nos connaissances sur le rôle de ces facteurs dans la régulation de l homéostasie énergétique et de l humeur, et propose un lien moléculaire entre diabète de type 2, obésité et dépressionInsulin and serotonin (5-HT) are two key players in the maintenance of energy homeostasis which is controlled by the hypothalamus. In this brain region, insulin mediates numerous metabolic effects via the activation of the PI3K/Akt signaling pathway. 5-HT exerts similar biological properties by acting in the hypothalamus but the signaling pathways accountable for these effects are still unclear. Moreover, it has been reported that 5-HT induces the activation of the PI3K/Akt pathway in the hippocampus and the inhibition of GSK3b, suggesting this action as a potential mechanism for the antidepressant effects of this neurotransmitter.The main objectives of this thesis were to study 1/ the serotonin-induced activation of the PI3K/Akt in the hypothalamus of wild type and diabetic rats (Goto-Kakizaki model) and search a potential cross-talk with insulin and, 2/ the mechanisms underlying the high-fat diet induced depression by investigating the role of the phosphorylation of Akt and GSK3b by 5-HT, insulin and leptin in the hippocampus of rats.Here, we show that 5-HT triggers the PI3K/Akt signaling pathway in the rat hypothalamus, and that this activation is attenuated in insulin-resistant conditions, suggesting a cross-talk between insulin and 5-HT. Moreover, we reported that high-fat diet feeding induces a reversible depressive-like behavior, which may involve the PI3K/Akt/GSK3b pathway in subgranular neurons of the dentate gyrus. In conclusion, the activation of the PI3K/Akt pathway and its target GSK3b by 5-HT in the hypothalamus and in the dentate gyrus, respectively, can be impaired in insulin-/leptin-resistant states, which may underlie a link between metabolic diseases and depression.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF