Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Androgen signaling, via the androgen receptor (AR), is crucial in mediating prostate cancer (PCa) initiation and progression. Identifying new downstream effectors of the androgens/AR pathway will allow a better understanding of these mechanisms and could reveal novel biomarkers and/or therapeutic agents to improve the rate of patient survival. We compared the microRNA expression profiles in androgen-sensitive LNCaP cells stimulated or not with 1 nM R1881 by performing a high-throughput reverse transcriptase-quantitative PCR and found that miR-135a was upregulated. After androgen stimulation, we showed that AR directly activates the transcription of miR-135a2 gene by binding to an androgen response element in the promoter region. Our findings identify miR-135a as a novel effector in androgens/AR signaling. Using xenograft experiments in chick embryos and adult male mice, we showed that miR-135a overexpression decreases in vivo invasion abilities of prostate PC-3 cells. Through in vitro wound-healing migration and invasion assays, we demonstrated that this effect is mediated through downregulating ROCK1 and ROCK2 expression, two genes that we characterized as miR-135a direct target genes. In human surgical samples from prostatectomy, we observed that miR-135a expression was lower in tumoral compared with paired adjacent normal tissues, mainly in tumors classified with a high Gleason score (⩾8). Moreover, miR-135a expression is lower in invasive tumors, showing extraprostatic extension, as compared with intraprostatic localized tumors. In tumor relative to normal glands, we also showed a more frequently higher ROCK1 protein expression determined using a semi-quantitative immunohistochemistry analysis. Therefore, in tumor cells, the lower miR-135a expression could lead to a higher ROCK1 protein expression, which could explain their invasion abilities. The highlighted relationship between miR-135a expression level and the degree of disease aggressiveness suggests that miR-135a may be considered as a prognostic marker in human PCa.Oncogene advance online publication, 28 July 2014; doi:10.1038/onc.2014.222.
ISSN: 0950-9232

hal-01063902
https://hal.archives-ouvertes.fr/hal-01063902
https://hal.archives-ouvertes.fr/hal-01063902/file/Androgen-regulated%20microRNA-135a.pdf
DOI : 10.1038/onc.2014.222
PUBMED : 25065599

Éditeur(s) : HAL CCSD
Résumé : International audience
Necroptosis is a regulated form of cell death involved in several disease models including in particular liver diseases. Receptor-interacting protein kinases, RIPK1 and RIPK3, are the main serine/threonine kinases driving this cell death pathway. We screened a noncommercial, kinase-focused chemical library which allowed us to identify Sibiriline as a new inhibitor of necroptosis induced by tumor necrosis factor (TNF) in Fas-associated protein with death domain (FADD)-deficient Jurkat cells. Moreover, Sib inhibits necroptotic cell death induced by various death ligands in human or mouse cells while not protecting from caspase-dependent apoptosis. By using competition binding assay and recombinant kinase assays, we demonstrated that Sib is a rather specific competitive RIPK1 inhibitor. Molecular docking analysis shows that Sib is trapped closed to human RIPK1 adenosine triphosphate-binding site in a relatively hydrophobic pocket locking RIPK1 in an inactive conformation. In agreement with its RIPK1 inhibitory property, Sib inhibits both TNF-induced RIPK1-dependent necroptosis and RIPK1-dependent apoptosis. Finally, Sib protects mice from concanavalin A-induced hepatitis. These results reveal the small-molecule Sib as a new RIPK1 inhibitor potentially of interest for the treatment of immune-dependent hepatitis. © 2017 Federation of European Biochemical Societies
ISSN: 1742464X

hal-01616420
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616420
DOI : 10.1111/febs.14176
PUBMED : 28715128

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 Elsevier
Résumé : International audience
Technologies for wireless telecommunication systems using millimeter waves (MMW) will be widely deployed in the near future. Forthcoming applications in this band, especially around 60 GHz, are mainly developed for high data-rate local and body-centric telecommunications. At those frequencies, electromagnetic radiations have a very shallow penetration into biological tissues, making skin keratinocytes, and free nerve endings of the upper dermis the main targets of MMW. Only a few studies assessed the impact of MMW on neuronal cells, and none of them investigated a possible effect on neuronal differentiation. We used a neuron-like cell line (PC12), which undergoes neuronal differentiation when treated with the neuronal growth factor (NGF). PC12 cells were exposed at 60.4 GHz for 24 h, at an incident power density averaged over the cell monolayer of 10 mW/cm2. Using a large scale cell-by-cell analysis based on high-content screening microscopy approach, we assessed potential effects of MMW on PC12 neurite outgrowth and cytoskeleton protein expression. No differences were found in protein expression of the neuronal marker β3-Tubulin nor in internal expression control β-Tubulin. On the other hand, our data showed a slight increase, although insignificant, in neurite outgrowth, induced by MMW exposure. However, experimental controls demonstrated that this increase was related to heating
ISSN: 0304-3940

hal-01281481
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01281481
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01281481/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01281481/file/Effects%20of%2060-GHz%20Millimeter%20Waves%20on%20Neurite.pdf
DOI : 10.1016/j.neulet.2016.02.038

Éditeur(s) : HAL CCSD Institute of Electrical and Electronics Engineers
Résumé : International audience
ISSN: 1536-1225

hal-01118086
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118086
DOI : 10.1109/LAWP.2014.2351780

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Emerging high data rate wireless communication systems, currently under development, will operate at millimeter waves (MMW) and specifically in the 60 GHz band for broadband short-range communications. The aim of this study was to investigate potential effects of MMW radiation on the cellular endoplasmic reticulum (ER) stress. Human skin cell lines were exposed at 60.4 GHz, with incident power densities (IPD) ranging between 1 and 20 mW/cm(2) . The upper IPD limits correspond to the ICNIRP local exposure limit for the general public. The expression of ER-stress sensors, namely BIP and ORP150, was then examined by real-time RT-PCR. Our experimental data demonstrated that MMW radiations do not change BIP or ORP150 mRNA basal levels, whatever the cell line, the exposure duration or the IPD level. Co-exposure to the well-known ER-stress inducer thapsigargin (TG) and MMW were then assessed. Our results show that MMW exposure at 20 mW/cm(2) inhibits TG-induced BIP and ORP150 over expression. Experimental controls showed that this inhibition is linked to the thermal effect resulting from the MMW exposure. Bioelectromagnetics. 35:444-451, 2014. © 2014 Wiley Periodicals, Inc.
ISSN: 0197-8462

hal-01063910
https://hal.archives-ouvertes.fr/hal-01063910
DOI : 10.1002/bem.21864
PUBMED : 25099539

Éditeur(s) : HAL CCSD
Résumé : International audience
The deformation of natural systems in response to subsurface water storage and redistribution provides insightsinto the main water flow path within heterogeneous systems, including the role of faults or fractures. A longbaseline tiltmeter was installed in the low-noise underground laboratory of Rustrel (LSBB) to study the responseof the Fontaine de Vaucluse (FDV) karst hydrosystem to water cycle. Tilt data and piezometric levels recorded in aborehole close to the LSBB show a strong correlation with the discharge of the system observed at the FDV spring30 km away. Over several months, tilt data were recorded on three base lines, thus allowing, for the first time,to study the tilt gradient variation that appears homogeneous. Such information provides a significant constrainton hydrological processes leading to the measured deformation. Several deformation models were tested usingthe ADELI code to estimate the type of hydro-mechanical structure that could reproduce the measured tilt andits gradient. On one hand, models show that uniform loading at the surface produces a much smaller signal thanobserved on measured data. On the other hand, the deformation related to the filling of a fracture following aprecipitation event requires unrealistic fracture size. Finally, we found that a suitable hydro-mechanical modelcorresponds to the loading of numerous fractures at the interface between the saturated and unsaturated zones. Sucha configuration predicts a tilt distribution in agreement with observations. This study suggests that tilt networksinto a karst system should provide key observation for deciphering hydrological processes
Geophysical Research Abstracts
Vienne, Austria

insu-01308594
https://hal-insu.archives-ouvertes.fr/insu-01308594

Éditeur(s) : HAL CCSD
Résumé : International audience
Extract the features for a multi-touch gesture is difficult due to the complex temporal and motion relations between multiple trajectories. In this paper we present a new generic graph model to quantify the shape, temporal and motion information from multi-touch gesture. To make a comparison between graph, we also propose a specific graph matching method based on graph edit distance. Results prove that our graph model can be fruitfully used for multi-touch gesture pattern recognition purpose with the classifier of graph embedding and SVM.
17th Biennial Conference of the International Graphonomics Society
Pointe-à-Pitre, Guadeloupe

hal-01165768
https://hal.univ-antilles.fr/hal-01165768
https://hal.univ-antilles.fr/hal-01165768/document
https://hal.univ-antilles.fr/hal-01165768/file/IGS_2015_submission_6.pdf

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
We study if the multilevel algorithm introduced by Debussche, T. Dubois and R. Temam [Theoret. Comput. Fluid Dynam. 7 (1995), no. 4, 279-315; Zbl 838.76060] and Dubois, F. Jauberteau and Temam [J. Sci. Comput. 8 (1993), no. 2, 167-194; MR1242960 (94f:65098)] for the 2D Navier-Stokes equations with periodic boundary conditions and spectral discretization can be generalized to more general boundary conditions and to finite elements. We first show that a direct generalization, as in [C. Calgaro, J. Laminie and R. Temam, Appl. Numer. Math. 23 (1997), no. 4, 403-442; MR1453424 (98d:76124)], for the Burgers equation, would not be very efficient. We then propose a new approach where the domain of integration is decomposed into subdomains. This enables us to define localized small-scale components and we show that, in this context, there is a good separation of scales. We conclude that all the ingredients necessary for the implementation of the multilevel algorithm are present.
ISSN: 0271-2091

hal-00730709
https://hal.archives-ouvertes.fr/hal-00730709

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
The etiology of congenital heart defect (CHD) combines environmental and genetic factors. So far, there were studies reporting on the screening of a single gene on unselected CHD or on familial cases selected for specific CHD types. Our goal was to systematically screen a proband of familial cases of CHD on a set of genetic tests to evaluate the prevalence of disease-causing variant identification. A systematic screening of GATA4, NKX2-5, ZIC3 and Multiplex ligation-dependent probe amplification (MLPA) P311 Kit was setup on the proband of 154 families with at least two cases of non-syndromic CHD. Additionally, ELN screening was performed on families with supravalvular arterial stenosis. Twenty-two variants were found, but segregation analysis confirmed unambiguously the causality of 16 variants: GATA4 (1 x), NKX2-5 (6 x), ZIC3 (3 x), MLPA (2 x) and ELN (4 x). Therefore, this approach was able to identify the causal variant in 10.4% of familial CHD cases. This study demonstrated the existence of a de novo variant even in familial CHD cases and the impact of CHD variants on adult cardiac condition even in the absence of CHD. This study showed that the systematic screening of genetic factors is useful in familial CHD cases with up to 10.4% elucidated cases. When successful, it drastically improved genetic counseling by discovering unaffected variant carriers who are at risk of transmitting their variant and are also exposed to develop cardiac complications during adulthood thus prompting long-term cardiac follow-up. This study provides an important baseline at dawning of the next-generation sequencing era.
ISSN: 1018-4813

hal-01404211
https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01404211
DOI : 10.1038/ejhg.2015.105
PUBMED : 26014430

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: The meiotic developmental pathway in yeast enables both differentiation of vegetative cells into haploid spores that ensure long-term survival, and recombination of the parental DNA to create genetic diversity. Despite the importance of proper metabolic regulation for the supply of building blocks and energy, little is known about the reprogramming of central metabolic pathways in meiotically differentiating cells during passage through successive developmental stages. Results: Metabolic regulation during meiotic differentiation in budding yeast was analyzed by integrating information on genome-wide transcriptional activity, 26 enzymatic activities in the central metabolism, the dynamics of 67 metabolites, and a metabolic flux analysis at mid-stage meiosis. Analyses of mutants arresting sporulation at defined stages demonstrated that metabolic reprogramming is tightly controlled by the progression through the developmental pathway. The correlation between transcript levels and enzymatic activities in the central metabolism varies significantly in a developmental stage-dependent manner. The complete loss of phosphofructokinase activity at mid-stage meiosis enables a unique setup of the glycolytic pathway which facilitates carbon flux repartitioning into synthesis of spore wall precursors during the co-assimilation of glycogen and acetate. The need for correct homeostasis of purine nucleotides during the meiotic differentiation was demonstrated by the sporulation defect of the AMP deaminase mutant amd1, which exhibited hyper-accumulation of ATP accompanied by depletion of guanosine nucleotides. Conclusions: Our systems-level analysis shows that reprogramming of the central metabolism during the meiotic differentiation is controlled at different hierarchical levels to meet the metabolic and energetic needs at successive developmental stages.
ISSN: 1471-2180

inserm-01094132
http://www.hal.inserm.fr/inserm-01094132
http://www.hal.inserm.fr/inserm-01094132/document
http://www.hal.inserm.fr/inserm-01094132/file/s12915-014-0060-x.pdf
DOI : 10.1186/s12915-014-0060-x