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Tudorie M.,Laboratoire Of Physique Des Lasers | Coudert L.H.,University Paris Est Creteil | Huet T.R.,Laboratoire Of Physique Des Lasers | Jegouso D.,Laboratoire Of Physique Des Lasers | Sedes G.,Laboratoire Of Physique Des Lasers
Journal of Chemical Physics | Year: 2011

The hyperfine structure of methyl formate was recorded in the 2-20 GHz range. A molecular beam coupled to a Fourier transform microwave spectrometer having an instrumental resolution of 0.46 kHz and limited by a Doppler width of a few kHz was used. A-type lines were found split by the magnetic hyperfine coupling while no splittings were observed for E-type lines. Symmetry considerations were used to account for the internal rotation of the methyl top and to derive effective hyperfine coupling Hamiltonians. Neglecting the spin-rotation magnetic coupling, the vanishing splittings of the E-type lines could be understood and analyses of the hyperfine patterns of the A-type lines were performed. The results are consistent with a hyperfine structure dominated by the magnetic spin-spin coupling due to the three hydrogen atoms of the methyl group. © 2011 American Institute of Physics.


Cerezo M.,French Institute of Health and Medical Research | Cerezo M.,University of Nice Sophia Antipolis | Lehraiki A.,French Institute of Health and Medical Research | Lehraiki A.,University of Nice Sophia Antipolis | And 49 more authors.
Cancer Cell | Year: 2016

We have discovered and developed a series of molecules (thiazole benzenesulfonamides). HA15, the lead compound of this series, displayed anti-cancerous activity on all melanoma cells tested, including cells isolated from patients and cells that developed resistance to BRAF inhibitors. Our molecule displayed activity against other liquid and solid tumors. HA15 also exhibited strong efficacy in xenograft mouse models with melanoma cells either sensitive or resistant to BRAF inhibitors. Transcriptomic, proteomic, and biochemical studies identified the chaperone BiP/GRP78/HSPA5 as the specific target of HA15 and demonstrated that the interaction increases ER stress, leading to melanoma cell death by concomitant induction of autophagic and apoptotic mechanisms. Cerezo et al. show that HA15, the lead compound of a series of thiazole benzenesulfonamides that they have developed, kills cancer cells by targeting BiP to increase ER stress. HA15 exhibits strong efficacy in melanoma cells, including those resistant to BRAF inhibitors. © 2016 Elsevier Inc.


Godard M.,University Paris - Sud | Godard M.,NASA | Feraud G.,CNRS Orsay Institute for Molecular Science | Chabot M.,University Paris - Sud | And 9 more authors.
EAS Publications Series | Year: 2012

Hydrogenated amorphous carbons, an important component of the interstellar carbonaceous dust, possess infrared spectral signatures (at 3.4, 6.9 and 7.3 μm) that are ubiquitous in the diffuse interstellar medium of galaxies, but not observed in dense clouds. To better understand the role played by cosmic rays in the disappearance of these absorption bands, irradiation experiments of hydrocarbon dust analogues have been performed with different swift ions. The results obtained through the in situ infrared monitoring of the samples during the irradiations allow to infer the dehydrogenation effect of the cosmic ray distribution on the interstellar hydrogenated amorphous carbons. The importance of this interstellar dust destruction by cosmic rays is discussed in comparison to other energetic processes in different interstellar environments. © The Author(s) 2013.


Borowiec A.-S.,French Institute of Health and Medical Research | Sion B.,University of Auvergne | Chalmel F.,French Institute of Health and Medical Research | Rolland A.D.,French Institute of Health and Medical Research | And 13 more authors.
FASEB Journal | Year: 2016

Testes of most male mammals present the particularity of being externalized from the body and are consequently slightly cooler than core body temperature (4-8°C below). Although, hypothermia of the testis is known to increase germ cells apoptosis, little is known about the underlying molecularmechanisms, including cold sensors, transduction pathways, and apoptosis triggers. In this study, using a functional knockoutmouse model of the cold and menthol receptors, dubbed transient receptor potential melastatine 8 (TRPM8) channels, we found that TRPM8 initiated the cold-shock response by differentially modulating cold- and heat-shock proteins. Besides, apoptosis of germ cells increased in proportion to the cooling level in control mice but was independent of temperature in knockout mice. We also observed that the rate of germcell death correlated positively with the reactive oxygen species level and negatively with the expression of the detoxifying enzymes. This result suggests that the TRPM8 sensor is a key determinant of germ cell fate under hypothermic stimulation.-Borowiec, A.-S., Sion, B., Chalmel, F., Rolland, A.D., Lemonnier, L.,De Clerck, T., Bokhobza, A., Derouiche, S.,Dewailly, E., Slomianny, C., Mauduit,C., Benahmed,M., Roudbaraki,M., Jegou,B., Prevarskaya, N.,Bidaux, G. Cold/mentholTRPM8receptors initiate thecold-shockresponseandprotect germcellsfromcold-shock-inducedoxidation. © The Author(s).


Quesada-Moreno M.M.,University of Jaén | Marquez-Garcia A.A.,University of Jaén | Aviles-Moreno J.R.,Laboratoire Of Physique Des Lasers | Lopez-Gonzalez J.J.,University of Jaén
Tetrahedron Asymmetry | Year: 2013

The biological relevance of amino acids is well known. They can be used as zwitterionic, cationic or anionic forms according to the pH of the medium where they are. Thus, our aim herein was to study the conformational preference of the polar amino acid l-threonine [C4H9NO3, (2S,3R)-2-amino-3-hydroxybutyric acid] under different pH conditions. A conformational study in an aqueous solution of the dissociation equilibrium of the amino acid l-threonine was carried out for this purpose. We recorded, at room temperature, the Mid-IR, Far-IR, Raman and VCD spectra of l-threonine from the aqueous solutions at pH values 5.70 (zwitterionic species), 1.00 (protonated species) and 13.00 (deprotonated species). The number of conformers found with the conformational search was 9 zwitterions, 27 anions and 52 cations. Both the study of the conformational landscape and the theoretical analysis of the vibrational features were accomplished by using DFT and ab initio calculations, that is, B3LYP/6-311++G(d,p) level of theory for all the conformers obtained from the conformational search, M062X/6-311++G(d,p) and MP2/6-311++G(d,p) levels of theory for the most stable conformers. The presence of water was included with the IEF-PCM implicit hydration model. With regard to the zwitterion, the importance of the analysis of the low frequency region (700-30 cm-1) in the Far-IR spectra should be noted, because it provides relevant information that can be used to determine the presence of the most stable structures. © 2013 Elsevier Ltd. All rights reserved.


Van Dorp M.,Catholic University of Leuven | Lannoo B.,Catholic University of Leuven | Lannoo B.,Laboratoire Of Physique Des Lasers | Carlon E.,Catholic University of Leuven
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2013

Using an improved version of an evolutionary algorithm originally proposed by François and Hakim, we generated small gene regulatory networks in which the concentration of a target protein oscillates in time. These networks may serve as candidates for oscillatory modules to be found in larger regulatory networks and protein interaction networks. The algorithm was run for 105 times to produce a large set of oscillating modules, which were systematically classified and analyzed. The robustness of the oscillations against variations of the kinetic rates was also determined, to filter out the least robust cases. Furthermore, we show that the set of evolved networks can serve as a database of models whose behavior can be compared to experimentally observed oscillations. The algorithm found three smallest (core) oscillators in which nonlinearities and number of components are minimal. Two of those are two-gene modules: the mixed feedback loop, already discussed in the literature, and an autorepressed gene coupled with a heterodimer. The third one is a single gene module which is competitively regulated by a monomer and a dimer. The evolutionary algorithm also generated larger oscillating networks, which are in part extensions of the three core modules and in part genuinely new modules. The latter includes oscillators which do not rely on feedback induced by transcription factors, but are purely of post-transcriptional type. Analysis of post-transcriptional mechanisms of oscillation may provide useful information for circadian clock research, as recent experiments showed that circadian rhythms are maintained even in the absence of transcription. © 2013 American Physical Society.


Bidaux G.,French Institute of Health and Medical Research | Bidaux G.,Lille University of Science and Technology | Bidaux G.,Laboratoire Of Physique Des Lasers | Borowiec A.-S.,French Institute of Health and Medical Research | And 32 more authors.
Oncotarget | Year: 2016

Since its cloning a decade ago, TRPM8 channel has emerged as a promising prognostic marker and a putative therapeutic target in prostate cancer (PCa). However, recent studies have brought to light the complexity of TRPM8 isoforms in PCa. Consequently, the respective role of each TRPM8 isoform needs to be deciphered prior to considering TRPM8 as an attractive therapeutic target. Full-length (6 transmembrane (TM)-domain) TRPM8 channel is overexpressed in early PCa and repressed in advanced prostate tumors whereas the localization of the truncated, 4TM-TRPM8 channel (4 transmembrane (TM)-domain), in the membranes of endoplasmic reticulum (ER) is independent of the pathogenic status of epithelial cells. In the same line, expression of non-channel cytoplasmic small TRPM8 isoforms (namely sM8) is conserved in cancer cells. In this study, we identify sM8s as putative regulator of PCa cell death. Indeed, suppression of sM8 isoforms was found to induce concomitantly ER stress, oxidative stress, p21 expression and apoptosis in human epithelial prostate cancer cells. We furthermore demonstrate that induction of such mechanisms required the activity of 4TM-TRPM8 channels at the ER-mitochondria junction. Our study thus suggests that targeting sM8 could be an appropriate strategy to fight prostate cancer.


Tudorie M.,Laboratoire Of Physique Des Lasers | Tudorie M.,Roosevelt University | Ilyushin V.,Ukrainian Academy of Sciences | Auwera J.V.,Roosevelt University | And 4 more authors.
Journal of Chemical Physics | Year: 2012

The far infrared spectrum of cis-methyl formate has been recorded on the AILES beamline of the synchrotron SOLEIL using a Fourier transform infrared spectrometer coupled to a long path cell. The very weak fundamental band associated with the methyl-top torsion mode (ν 18) was observed. The frequency analysis was performed using the rho axis method, and the microwave and millimeter-wave data from the literature. A precise determination of the band origins (ν18A 132.4303 cm -1 and ν18E 131.8445 cm -1) and of the barrier height V 3 370.7398 (58) cm -1 have been obtained. The intensity of the ν 18 fundamental band was determined to be 3.4 × 10 -21 cm -1(molecule cm -2) at 297 K, equally shared among A-A and E-E transitions, thus leading to a dipole moment component μ c (3) equal to 0.0483 D. The results were compared with the ab initio calcula-tions of Senent [Astrophys. J. 627, 567 (2005)]10.1086/430201. © 2012 American Institute of Physics.


PubMed | Laboratoire Of Physique Des Lasers, University of Nice Sophia Antipolis, French Institute of Health and Medical Research, CNRS Gustave Roussy Institute and 3 more.
Type: Journal Article | Journal: Cancer cell | Year: 2016

We have discovered and developed a series of molecules (thiazole benzenesulfonamides). HA15, the lead compound of this series, displayed anti-cancerous activity on all melanoma cells tested, including cells isolated from patients and cells that developed resistance to BRAF inhibitors. Our molecule displayed activity against other liquid and solid tumors. HA15 also exhibited strong efficacy in xenograft mouse models with melanoma cells either sensitive or resistant to BRAF inhibitors. Transcriptomic, proteomic, and biochemical studies identified the chaperone BiP/GRP78/HSPA5 as the specific target of HA15 and demonstrated that the interaction increases ER stress, leading to melanoma cell death by concomitant induction of autophagic and apoptotic mechanisms.


PubMed | Laboratoire Of Physique Des Lasers and French Institute of Health and Medical Research
Type: Journal Article | Journal: Oncotarget | Year: 2016

Since its cloning a decade ago, TRPM8 channel has emerged as a promising prognostic marker and a putative therapeutic target in prostate cancer (PCa). However, recent studies have brought to light the complexity of TRPM8 isoforms in PCa. Consequently, the respective role of each TRPM8 isoform needs to be deciphered prior to considering TRPM8 as an attractive therapeutic target. Full-length (6 transmembrane (TM)-domain) TRPM8 channel is overexpressed in early PCa and repressed in advanced prostate tumors whereas the localization of the truncated, 4TM-TRPM8 channel (4 transmembrane (TM)-domain), in the membranes of endoplasmic reticulum (ER) is independent of the pathogenic status of epithelial cells. In the same line, expression of non-channel cytoplasmic small TRPM8 isoforms (namely sM8) is conserved in cancer cells. In this study, we identify sM8s as putative regulator of PCa cell death. Indeed, suppression of sM8 isoforms was found to induce concomitantly ER stress, oxidative stress, p21 expression and apoptosis in human epithelial prostate cancer cells. We furthermore demonstrate that induction of such mechanisms required the activity of 4TM-TRPM8 channels at the ER-mitochondria junction. Our study thus suggests that targeting sM8 could be an appropriate strategy to fight prostate cancer.

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