Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The current design studies on sodium-cooled fast reactors (SFRs) are breaking with the past since they are guided by a new set of design criteria arising from the objectives of Generation IV reactors. The new safety requirements lead to designing reactors with breakeven breeding cores because in terms of reactivity control, they minimize the need to limit the consequences of an inadvertent control rod withdrawal event. Furthermore, as the reactivity control needs are low, a breakeven core enables the use of absorbing materials with reduced efficiency (natural boron, hafnium, etc.), which may be less costly than enriched boron. However, control rods designed with low absorbing materials may present the disadvantage of a nonnegligible loss of efficiency due to their consumption under irradn. This paper presents a methodol. to accurately calc. and to analyze the impact of this consumption on reactivity control.
ISSN: 0302-2927

hal-01088526
https://hal.archives-ouvertes.fr/hal-01088526
DOI : 10.13182/NSE13-59

Éditeur(s) : HAL CCSD Optical Society Optical Society - SOA Publishing
Résumé : International audience
We show that the canonical single frequency sarcomeric SHG intensity pattern (SHG-IP) of control muscles is converted to double frequency sarcomeric SHG-IP in preserved mdx mouse gastrocnemius muscles in the vicinity of necrotic fibers. These double frequency sarcomeric SHG-IPs are often spatially correlated to double frequency sarcomeric two-photon excitation fluorescence (TPEF) emitted from Z-line and I-bands and to one centered spot SHG angular intensity pattern (SHG-AIP) suggesting that these patterns are signature of myofibrillar misalignement. This latter is confirmed with transmission electron microscopy (TEM). Moreover, a good spatial correlation between SHG signature of myofibrillar misalignment and triad reduction is established. Theoretical simulation of sarcomeric SHG-IP is used to demonstrate the correlation between change of SHG-IP and -AIP and myofibrillar misalignment. The extreme sensitivity of SHG microscopy to reveal the submicrometric organization of A-band thick filaments is highlighted. This report is a first step toward future studies aimed at establishing live SHG signature of myofibrillar misalignment involving excitation contraction defects due to muscle damage and disease.
ISSN: 2156-7085

hal-00952823
https://hal.archives-ouvertes.fr/hal-00952823
https://hal.archives-ouvertes.fr/hal-00952823/document
https://hal.archives-ouvertes.fr/hal-00952823/file/boe-5-3-858_002.pdf
DOI : 10.1364/BOE.5.000858

Éditeur(s) : HAL CCSD
Résumé : IPC: C07D 311/60 (2006.01), A61K 31/352 (2006.01), A61P 29/00 (2006.01), A61P 35/00 (2006.01), A61P 37/00 (2006.01), C07D 311/64 (2006.01), C07D 335/06 (2006.01), C07D 407/04 (2006.01), C07D 409/04 (2006.01)
The invention relates to new PI3K/AKT/mTOR inhibitors of formula (I) and their use for the prevention and/or the treatment of a disease selected from the group consisting of: inflammatory diseases, autoimmune diseases, neurodegenerative diseases, cancers, transplant rejection, diseases characterized by a premature aging and tuberous sclerosis.
L'invention concerne de nouveaux inhibiteurs de PI3K/AKT/mTOR, et leur utilisation pour la prévention et/ou le traitement d'une maladie choisie dans le groupe constitué par: des maladies inflammatoires, des maladies auto-immunes, des maladies neurodégénératives, des cancers, un rejet de greffe, des maladies caractérisées par un vieillissement prématuré ou la sclérose tubéreuse.
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139914

Patent N° : WO 2015044229 / EP 2853530
hal-01139914
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139914

Éditeur(s) : Pergamon-elsevier Science Ltd
Résumé : We tested the applicability of the BIT (branched and isoprenoid tetraether) index as a proxy for palaeoflood events in the river-dominated continental margin of the Gulf of Lions (NW Mediterranean). We compared the concentrations of branched glycerol dialkyl glycerol tetraethers (br GDGTs) and crenarchaeol in suspended particulate matter (SPM) collected downstream in the Rhône River, as well as in surface sediments and a ca. 8m piston core from the Rhône prodelta. The core covered the last 400 yr, with four distinct intervals recording the river influence under natural and man-induced shifts in four main channels of the river mouth (Bras de Fer, Grand Rhône, Pégoulier,and Roustan). The results indicate that there are mixed sources of br GDGTs and crenarchaeol in the prodelta, complicating applicationof the BIT index as an indicator of continental organic carbon input and thus as a palaeoflood proxy. However, the sedimentary BIT record for the period when continental material was delivered by the river more directly to the core site (Roustan phase;1892 to present) mimics the historical palaeoflood record. This shows the potential of the BIT index as a palaeoflood proxy, provided that the delivery route of the continental material by rivers to the core sites remains constant over time. The study also highlights the idea that shifts in river channels should be taken into account for the use of the BIT index as a palaeoflood proxy.
Organic Geochemistry (0146-6380) (Pergamon-elsevier Science Ltd), 2014-10 , Vol. 75 , P. 99-108

Droits : 2014 Elsevier Ltd. All rights reserved.
http://archimer.ifremer.fr/doc/00198/30969/29345.pdf
DOI:10.1016/j.orggeochem.2014.06.011
http://archimer.ifremer.fr/doc/00198/30969/

Éditeur(s) : HAL CCSD American Society for Biochemistry and Molecular Biology
Résumé : International audience
Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (B(a)P) are widely distributed environmental contaminants, known as potent ligands of the aryl hydrocarbon receptor (AhR). These chemicals trigger an early and transient increase of intracellular calcium concentration ([Ca(2+)](i)), required for AhR-related effects of PAHs. The mechanisms involved in this calcium mobilization were investigated in the present study. We demonstrated that B(a)P-mediated [Ca(2+)](i) induction was prevented in endothelial HMEC-1 cells by counteracting β2-adrenoreceptor (β2ADR) activity using pharmacological antagonists, anti-β2ADR antibodies, or siRNA-mediated knockdown of β2ADR expression; by contrast, it was strongly potentiated by β2ADR overexpression in human kidney HEK293 cells. B(a)P was shown, moreover, to directly bind to β2ADR, as assessed by in vitro binding assays and molecular modeling. Pharmacological inhibition and/or siRNA-mediated silencing of various signaling actors acting downstream of β2ADR in a sequential manner, such as G protein, adenylyl cyclase, Epac-1 protein, and inositol 1,4,5-trisphosphate (IP(3))/IP(3) receptor, were next demonstrated to prevent B(a)P-induced calcium signal. Inhibition or knockdown of these signaling elements, as well as the use of chemical β-blockers, were finally shown to counteract B(a)P-mediated induction of cytochrome P-450 1B1, a prototypical AhR target gene. Taken together, our results show that B(a)P binds directly to β2ADR and consequently utilizes β2ADR machinery to mobilize [Ca(2+)](i), through activation of a G protein/adenylyl cyclase/cAMP/Epac-1/IP(3) pathway. This β2ADR-dependent signaling pathway activated by PAHs may likely be crucial for PAH-mediated up-regulation of AhR target genes, thus suggesting a contribution of β2ADR to the health-threatening effects of these environmental pollutants.
ISSN: 0021-9258

hal-00682497
https://hal.archives-ouvertes.fr/hal-00682497
DOI : 10.1074/jbc.M111.319970
PUBMED : 22167199

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Polarization dependence second harmonic generation (P-SHG) microscopy is gaining increase popularity for in situ quantification of fibrillar protein architectures. In this report, we combine P-SHG microscopy, new linear least square (LLS) fitting and modeling to determine and convert the complex second-order non-linear optical anisotropy parameter ρ of several collagen rich tissues into a simple geometric organization of collagen fibrils. Modeling integrates a priori knowledge of polyhelical organization of collagen molecule polymers forming fibrils and bundles of fibrils as well as Poisson photonic shot noise of the detection system. The results, which accurately predict the known sub-microscopic hierarchical organization of collagen fibrils in several tissues, suggest that they can be subdivided into three classes according to their microscopic and macroscopic hierarchical organization of collagen fibrils. They also show, for the first time to our knowledge, intrahepatic spatial discrimination between genuine fibrotic and non-fibrotic vessels. CCl 4-treated livers are characterized by an increase in the percentage of fibrotic vessels and their remodeling involves peri-portal compaction and alignment of collagen fibrils that should contribute to portal hypertension. This integrated P-SHG image analysis method is a powerful tool that should open new avenue for the determination of pathophysiological and chemo-mechanical cues impacting collagen fibrils organization.
ISSN: 2045-2322

hal-01592192
https://hal.archives-ouvertes.fr/hal-01592192
https://hal.archives-ouvertes.fr/hal-01592192/document
https://hal.archives-ouvertes.fr/hal-01592192/file/s41598-017-12398-0.pdf
DOI : 10.1038/s41598-017-12398-0

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
: We investigated the in vitro effects of four alkyl-galactofuranoside derivatives, i.e. octyl-β-D-galactofuranoside (1), 6-amino-β-D-galactofuranoside (2), 6-N-acetamido-β-D-galactofuranoside (3), and 6-azido-β-D-galactofuranoside (4) on Leishmania donovani. Their mechanism of action was explored using electron paramagnetic resonance spectroscopy (EPR) and nuclear magnetic resonance (NMR), and ultrastructural alterations by transmission electron microscopy (TEM). Compound 1 showed the most promising effects by inhibiting promastigote growth at IC50 8.96 ± 2.5 μM. All compounds exhibit low toxicity towards human macrophages. Compound 1 had a higher selectivity index than the comparative molecule used, i.e. miltefosine (159.7 versus 37.9, respectively). EPR showed that compound 1 significantly reduced membrane fluidity, compared to control promastigotes and to compound 3. The furanose ring was shown to support this effect since the isomer galactopyranose had no effect on parasite membrane fluidity or growth. NMR showed a direct interaction of all compounds (1>2>3>4) with the promastigote membrane, as well as with octyl-galactopyranose and octanol, providing evidence that the n-octyl chain was primarily involved in the anchoring with the parasite membrane, followed by the putative crucial role of furanose ring in the anti-leishmanial activity. A morphologic analysis of compound 1-treated promastigotes by TEM revealed profound alterations on parasite membrane and organelles, but not with compound 3. Quantification of annexinV binding by flow cytometry confirmed that compound 1 induced apoptosis in >90% promastigotes. The effect of compound 1 was also assessed on intra-macrophagic amastigotes, and showed a reduction in amastigote growth associated with an increase of ROS production, thus validating its promising effect.
ISSN: 0066-4804

hal-00941772
https://hal.archives-ouvertes.fr/hal-00941772
PUBMED : 24468785
DOI : 10.1128/AAC.01350-13

Éditeur(s) : HAL CCSD Optical Society of America
Résumé : International audience
A linear least square (LLS) method is proposed to process polarization dependent SHG intensity analysis at pixel-resolution level in order to provide an analytic solution of nonlinear susceptibility χ(2) coefficients and of fibril orientation. This model is applicable to fibrils with identical orientation in the excitation volume. It has been validated on type I collagen fibrils from cell-free gel, tendon and extracellular matrix of F1 biliary epithelial cells. LLS is fast (a few hundred milliseconds for a 512 × 512 pixel image) and very easy to perform for non-expert in numerical signal processing. Theoretical simulation highlights the importance of signal to noise ratio for accurate determination of nonlinear susceptibility χ(2) coefficients. The results also suggest that, in addition to the peptide group, a second molecular nonlinear optical hyperpolarizability β contributes to the SHG signal. Finally from fibril orientation analysis, results show that F1 cells remodel extracellular matrix collagen fibrils by changing fibril orientation, which might have important physiological function in cell migration and communication.
ISSN: 1094-4087

hal-01139871
https://hal.archives-ouvertes.fr/hal-01139871
DOI : 10.1364/OE.23.013309
PUBMED : 26074581

Éditeur(s) : Paris : Imprimerie des Journaux officiels
Résumé : Extrait du Journal Officiel des 14 et 17 décembre 1912
Siècle(s) traité(s) : 20
Droits : Domaine public
Provenance : Collectivité territoriale de Guyane. Bibliothèque Alexandre-Franconie
Permalien : http://www.manioc.org/patrimon/FRA12050
FRA12050

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Second harmonic generation (SHG) microscopy is a powerful tool for studying submicron architecture of muscles tissues. Using this technique, we show that the canonical single frequency sarcomeric SHG intensity pattern (SHG-IP) of premetamorphic xenopus tadpole tail muscles is converted to double frequency (2f) sarcomeric SHG-IP in metamorphic climax stages due to massive physiological muscle proteolysis. This conversion was found to rise from 7% in premetamorphic muscles to about 97% in fragmented muscular apoptotic bodies. Moreover a 66% conversion was also found in non-fragmented metamorphic tail muscles. Also, a strong correlation between predominant 2f sarcomeric SHG-IPs and myofibrillar misalignment is established with electron microscopy. Experimental and theoretical results demonstrate the higher sensitivity and the supra resolution power of SHG microscopy over TPEF to reveal 3D myofibrillar misalignment. From this study, we suggest that 2f sarcomeric SHG-IP could be used as signature of triad defect and disruption of excitation–contraction coupling. As the mechanism of muscle proteolysis is similar to that found in mdx mouse muscles, we further suggest that xenopus tadpole tail resorption at climax stages could be used as an alternative or complementary model of Duchene muscular dystrophy.
ISSN: 1047-8477

hal-01134174
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134174
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134174/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134174/file/Recher%20et%20al_JSB-2015_hal.pdf
DOI : 10.1016/j.jsb.2015.03.003

Éditeur(s) : HAL CCSD Royal Society of Chemistry
Résumé : International audience
ISSN: 2046-2069

hal-01116129
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01116129
DOI : 10.1039/C3RA47255H

Éditeur(s) : HAL CCSD Wiley-VCH Verlag
Résumé : International audience
Deciphering the assembly history of the Milky Way is a formidable task, which becomes possible only if one can produce high-resolution chrono-chemo-kinematical maps of the Galaxy. Data from large-scale astrometric and spectroscopic surveys will soon provide us with a well-defined view of the current chemo-kinematical structure of the Milky Way, but will only enable a blurred view on the temporal sequence that led to the present-day Galaxy. As demonstrated by the (ongoing) exploitation of data from the pioneering photometric missions CoRoT, Kepler, and K2, asteroseismology provides the way forward: solar-like oscillating giants are excellent evolutionary clocks thanks to the availability of seismic constraints on their mass and to the tight age-initial-mass relation they adhere to. In this paper we identify five key outstanding questions relating to the formation and evolution of the Milky Way that will need precise and accurate ages for large samples of stars to be addressed, and we identify the requirements in terms of number of targets and the precision on the stellar properties that are needed to tackle such questions. By quantifying the asteroseismic yields expected from PLATO for red-giant stars, we demonstrate that these requirements are within the capabilities of the current instrument design, provided that observations are sufficiently long to identify the evolutionary state and allow robust and precise determination of acoustic-mode frequencies. This will allow us to harvest data of sufficient quality to reach a 10% precision in age. This is a fundamental pre-requisite to then reach the more ambitious goal of a similar level of accuracy, which will only be possible if we have to hand a careful appraisal of systematic uncertainties on age deriving from our limited understanding of stellar physics, a goal which conveniently falls within the main aims of PLATO's core science.
ISSN: 0004-6337

hal-01541393
https://hal.archives-ouvertes.fr/hal-01541393
ARXIV : 1706.3778
BIBCODE : 2017AN....338..644M
DOI : 10.1002/asna.201713385

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
A thorough phytochemical study of Stereocaulon evolutum was conducted, for the isolation of structurally related atranorin derivatives. Indeed, pilot experiments suggested that atra-norin (1), the main metabolite of this lichen, would interfere with the lifecycle of hepatitis C virus (HCV). Eight compounds, including one reported for the first time (2), were isolated and characterized. Two analogs (5, 6) were also synthesized, to enlarge the panel of atra-norin-related structures. Most of these compounds were active against HCV, with a half-maximal inhibitory concentration of about 10 to 70 µM, with depsides more potent than monoaromatic phenols. The most effective inhibitors (1, 5 and 6) were then added at different steps of the HCV lifecycle. Interestingly, atranorin (1), bearing an aldehyde function at C-3, inhibited only viral entry, whereas the synthetic compounds 5 and 6, bearing a hydroxy-methyl and a methyl function, respectively, at C-3 interfered with viral replication.
ISSN: 1932-6203

hal-01134343
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134343
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134343/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134343/file/Depsides-PloS.pdf
DOI : 10.1371/journal.pone.0120405

Éditeur(s) : HAL CCSD Biophysical Society
Résumé : International audience
SHG angular intensity pattern (SHG-AIP) of healthy and proteolysed muscle tissues are simulated and imaged here for the first time to our knowledge. The role of the spatial distribution of second-order nonlinear emitters on SHG-AIP is highlighted. SHG-AIP with two symmetrical spots is found to be a signature of healthy muscle whereas SHG-AIP with one centered spot in pathological mdx muscle is found to be a signature of myofibrillar disorder. We also show that SHG-AIP provides information on the three-dimensional structural organization of myofibrils in physiological and proteolysed muscle. Our results open an avenue for future studies aimed at unraveling more complex physiological and pathological fibrillar tissues organization.
ISSN: 0006-3495

hal-00825645
https://hal.archives-ouvertes.fr/hal-00825645
https://hal.archives-ouvertes.fr/hal-00825645/document
https://hal.archives-ouvertes.fr/hal-00825645/file/Theoretical-SHG-accepted.pdf
DOI : 10.1016/j.bpj.2013.02.047

Éditeur(s) : HAL CCSD American Physical Society
Résumé : International audience
It is getting increasingly evident that physical properties such as elastoviscoplastic properties of living materials are quite important for the process of tissue development, including regulation of genetic pathways. Measuring such properties in vivo is a complicated and challenging task. In this paper, we present an instrument, a scanning air puff tonometer, which is able to map point by point the viscoelastic properties of flat or gently curved soft materials. This instrument is an improved version of the air puff tonometer used by optometrists, with important modifications. The instrument allows one to obtain a direct insight into gradients of material properties in vivo. The instrument capabilities are demonstrated on substances with known elastoviscoplastic properties and several biological objects. On the basis of the results obtained, the role of the gradients of elastoviscoplastic properties is outlined for the process of angiogenesis, limb development, bacterial colonies expansion, etc. which is important for bridging the gaps in the theory of the tissue development and highlighting new possibilities for tissue engineering, based on a clarification of the role of physical features in developing biological material.
ISSN: 1539-3755

hal-00666187
https://hal.archives-ouvertes.fr/hal-00666187
https://hal.archives-ouvertes.fr/hal-00666187/document
https://hal.archives-ouvertes.fr/hal-00666187/file/FLEURY_PRE_2010.pdf
DOI : 10.1103/PhysRevE.81.021920

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Meconium is the earliest stool of newborns, and is a complex matrix that reflects the degree of exposure of the fetus to xenobiotics. To investigate fetal exposure to volatile organic compounds, an analytical method was developed to identify and quantify BTEX (benzene, toluene, ethylbenzene, and o,m,p-xylene) and two chlorinated solvents (trichloroethylene and tetrachloroethylene) in meconium. Headspace-solid-phase microextraction coupled with gas chromatography-mass spectrometry was selected because it is simple, sensitive, can be automated, and requires no extensive sample preparation. Several extraction variables were optimized (fiber type, incubation time, temperature of fiber, and use of salt). Because meconium is a complex matrix, quantification by SPME was considered carefully because of potential interference, for example competitive adsorption. Calibration in water was compared with calibration in meconium using external and internal methods (with isotope-labeled compounds). In meconium, limits of quantification were determined to be in the range 0.064-0.096 ng g(-1) for the investigated compounds. All target compounds were determined in "real-case" meconium samples.
ISSN: 1618-2642

hal-01064967
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01064967
DOI : 10.1007/s00216-014-7836-2
PUBMED : 24838489

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Chaperone synthesis in response to proteotoxic stress is dependent on a family of transcription factors named heat shock factors (HSFs). The two main factors in this family, HSF1 and HSF2, are co-expressed in numerous tissues where they can interact and form heterotrimers in response to proteasome inhibition. HSF1 and HSF2 exhibit two alternative splicing isoforms, called α and β, which contribute to additional complexity in HSF transcriptional regulation, but remain poorly examined in the literature. In this work, we studied the transcriptional activity of HSF1 and HSF2 splicing isoforms transfected into immortalized Mouse Embryonic Fibroblasts (iMEFs) deleted for both Hsf1 and Hsf2, under normal conditions and after proteasome inhibition. We found that HSF1α is significantly more active than the β isoform after exposure to the proteasome inhibitor MG132. Furthermore, we clearly established that, while HSF2 had no transcriptional activity by itself, short β isoform of HSF2 exerts a negative role on HSF1β-dependent transactivation. To further assess the impact of HSF2β inhibition on HSF1 activity, we developed a mathematical modelling approach which revealed that the balance between each HSF isoform in the cell regulated the strength of the transcriptional response. Moreover, we found that cellular stress such as proteasome inhibition could regulate the splicing of Hsf2 mRNA. All together, our results suggest that relative amounts of each HSF1 and HSF2 isoforms quantitatively determine the cellular level of the proteotoxic stress response.
ISSN: 1932-6203

inserm-00814784
http://www.hal.inserm.fr/inserm-00814784
http://www.hal.inserm.fr/inserm-00814784/document
http://www.hal.inserm.fr/inserm-00814784/file/journal.pone.0056085.pdf
DOI : 10.1371/journal.pone.0056085

Éditeur(s) : HAL CCSD
Rencontres Biologie Physique RBPGO4
Berder, France

hal-00919259
https://hal.archives-ouvertes.fr/hal-00919259

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé :  
We compared floral odour profiles among populations of two Arum species which show different degrees of specificity for their fly pollinators. Insects were collected from inflorescences in four populations of Arum italicum and two populations of Arum maculaturn. In six Arum populations, we compared inflorescences odour profiles collected by Solid Phase Micro Extraction (SPME) and analysed by gas chromatography. We confirmed that from a pollination point of view, A. italicum is an opportunist species, as it is mainly pollinated by insects of the families Psychodidae, Chironomidae and Sciaridae, whereas A. maculatum is a specialist species, as it is 90% pollinated by Psychodidae. In all populations, Arum italicum was less attractive to pollinators than Arum maculatum. Floral odour profiles of A. italicum were not geographically structured among populations, suggesting a high gene flow or adaptation to a fluctuant guild of pollinators. On the contrary, odour profiles of A. maculatum varied between the two populations studied suggesting a lower gene flow or adaptation to different local pollinator preferences
ISSN: 0037-9271

hal-01019003
https://hal.archives-ouvertes.fr/hal-01019003

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 0168-583X

hal-01685822
https://hal.univ-antilles.fr/hal-01685822
DOI : 10.1016/0168-583X(90)90675-K