Articles
Yves-Henri Sanejouand

US2B, UMR 6286 du CNRS, Bat.25, Bureau 8, Faculte des Sciences et des Techniques, 2, rue de la Houssiniere, 44322 Nantes Cedex 3, France. Tel: +33 (0) 2 51 12 57 76; .

Reload several times to see, at random, my face (at rest, at work abroad, at work in my previous lab), a Discrete Breather poping up or jumping to another site (within the frame of a non-linear network model of proteins), a N-neighbor Elastic Network Model, a water channel inside a glycoside hydrolase, or the predicted 3D domain-swapping motion of CD4...

Most of my work has turned around the (normal, harmonic, linear, or not) modes of proteins and their relationship with function. However, I also worked on the sequence-structure relationship, on unknown proteins, host-virus interactions, as well as on force-field parametrization, and used standard methods to study various systems, like the NMDA receptor, antibodies, parvalbumin or glycoside hydrolases, within the frame of a collaboration with the glycobiology team of US2B (formerly called UFIP, U3B). I am also interested by other fields.

My bash scripts and fortran softwares for normal mode analysis are here. Bash one-liners I found useful are there.

Protein normal modes:

Sanejouand, Y.H. (2021): "Normal-mode driven exploration of protein domain motions", J. Comput. Chem., vol.42 (31), p2250-2257, DOI 10.1002/jcc.26755. Submitted version: arXiv 2103.11959. Where it is shown that, with the help of ROSETTA, it is possible to build crystal-like conformers close to actual endpoints of known conformational changes, using the values of at most six normal coordinates. Like in our previous study on this topic, model conformers were generated from normal mode coordinates with dq_modes, normal modes being obtained with enm_modes.

Sanejouand, Y.H. (2021): "On the vibrational free energy of hydrated proteins", Phys. Biol., vol.18 (3), 036003, DOI 10.1088/1478-3975/abdc0f. Submitted version: arXiv 2010.10313. Where it is shown that there is a significant anti-correlation between the vibrational free energy and the potential energy of proteins hydrated with more than 0.6 gram of water per gram.

Mahajan, S. & Sanejouand, Y.H. (2017): "Jumping between protein conformers using normal modes", J. Comput. Chem., vol.38, p1622-1630 , DOI 10.1002/jcc.24803. Where it is shown that, with the help of ROSETTA, mode following can yield crystal-like conformers close to actual endpoints of known conformational changes. Model conformers were generated from normal mode coordinates using dq_modes. Normal modes were obtained with enm_modes.

Mahajan, S. & Sanejouand, Y.H. (2015): "On the relationship between low-frequency normal modes and the large-scale conformational changes of proteins", Archives of Biochemistry and Biophysics, vol.567, p59-65 , DOI 10.1016/j.abb.2014.12.020. A short review, with some emphasis on the applications derived from this relationship.

Sanejouand, Y.H. (2015): "Simplified flexibility analysis of proteins" in Computational Approaches to Protein Dynamics: from Quantum to Coarse-Grained Methods, p154-177, Monika Fuxreiter ed., CRC Press; arXiv 1312.5639. A short review, with some emphasis on the interest of the highest-frequency modes of protein elastic networks.

Sanejouand, Y.H. (2012): "Elastic Network Models: Theoretical and Empirical Foundations" in Biomolecular simulations: Methods and Protocols, Methods in Molecular Biology, vol.924, p601-616, Emppu Salonen, Luca Monticelli eds, Humana Press, Springer; arXiv 1102.2402.

Sanejouand, Y.H. (2007): "Les modes normaux de vibration de basse frequence des proteines". Habilitation a diriger des recherches, Universite de Lyon-I (in french).

Suhre, K., Navaza, J., & Sanejouand, Y.H. (2006): "NORMA: a tool for flexible fitting of high resolution protein structures into low resolution electron microscopy derived density maps", Acta Cryst. D, vol.62(9), p1098-1100 . NORMA can be downloaded here.

Nicolay, S., & Sanejouand, Y.H. (2006): "Functional modes of proteins are among the most robust", Phys. Rev. letters, vol.96, 078104 ; arXiv 0509020, where modes obtained with standard Elastic Network Models are compared to those obtained with a N-neighbor one, the most robust ones being found to be likely involved in function.

Sanejouand, Y.H. (2005): "Functional information from slow mode shapes", in Normal Mode Analysis: Theory and Applications to Biological and Chemical Systems, C&H/CRC Mathematical & Computational Biology Series, vol. 9, p91-109. Ivet Bahar & Qiang Cui eds, CRC press (A book with contributions from L. Mouawad & D. Perahia, I. Bahar, Q. Cui, C.L. Brooks & F. Tama, J.P. Ma, G.N. Phillips, H. Van Vlijmen, J. Bowman, etc, and a foreword from M. Karplus).

Suhre, K., & Sanejouand, Y.H. (2004): " ElNemo: a normal mode server for protein movement analysis and the generation of templates for molecular replacement", Nucl. Ac. Res. vol.32 (Web server issue), pW610-W614 .

Suhre, K., & Sanejouand, Y.H. (2004): "On the potential of normal mode analysis for solving difficult molecular replacement problems", Acta Cryst. D vol.60, p796-799 .

Sanejouand, Y.H. (2004): "Protein functional dynamics: computational approaches", in Energy localisation and transfer in crystals, biomolecules and josephson arrays, Advanced Series in Nonlinear Dynamics, vol.22, p273-300. Thierry Dauxois, Anna Litvak-Hinenzon, Robert MacKay & Anna Spanoudaki eds, World Scientific.

Valadie, H., Lacapere, J.J., Sanejouand, Y.H., & Etchebest, C. (2003): "Dynamical properties of the MscL of Escherichia coli: A normal mode analysis", J. Mol. Biol. vol.332, p657-674.

Elezgaray, J., Marcou, G., & Sanejouand, Y.H. (2002): "Exploring the natural conformational changes of the C-terminal domain of calmodulin", Phys. Rev. E vol. 66, p31908-31915.

Delarue, M., & Sanejouand, Y.H. (2002): "Simplified normal modes analysis of conformational transitions in DNA-dependant polymerases: the Elastic Network Model", J. Mol. Biol. vol.320, p1011-1024, where previous results are confirmed while the importance of protein shape is underlined.

Tama, F., & Sanejouand, Y.H. (2001) : "Conformational change of proteins arising from normal modes calculations", Protein Engineering vol.14, p1-6, where the link between protein large-amplitude conformational changes and their low-frequency modes is confirmed, even when the latter are obtained with an Elastic Network Model. Moreover, the limits of this relationship are exhibited. PDBMAT, the corresponding stand-alone software, is available here.

Elezgaray, J., Marcou, G., & Sanejouand, Y.H. (2001): "Coupling overall rotations with modal dynamics", Theor. Chem. Acc. vol.106, p62-68.

Elezgaray, J., & Sanejouand, Y.H. (2000): "Modal dynamics of proteins in water", J. Comput. Chem. vol.21, p1274-1282.

Tama, F., Gadea, F.X., Marques, O., & Sanejouand, Y.H. (2000) : "Building-block approach for determining low-frequency normal modes of macromolecules", Proteins: Structure, Function and Genetics vol.41(1), p1-7, where the RTB approximation is used for calculating the low-frequency normal modes of large proteins. DIAGRTB, the corresponding stand-alone software, is available here.

Elezgaray, J., & Sanejouand, Y.H. (1998): "Modeling large-scale dynamics of proteins", Biopolymers vol.46, p493-501.

Marques, O., & Sanejouand, Y.H. (1995) : "Hinge-bending motion in citrate synthase arising from Normal Mode calculations", Proteins: Structure, Function and Genetics, vol.23, p557-560 (Scanned: 6 Mo).

Sanejouand, Y.H., & Tapia, O. (1995): "Low-frequency domain motions in the Carboxy Terminal Fragment of the L7/L12 Ribosomal Protein studied with MD techniques : Are these movements model independant ?", J. Phys. Chem., vol.99, p5698-5704. (Scanned: 9 Mo)

Durand, P., Trinquier, G., & Sanejouand, Y.H. (1994) : "A new approach for determining low-frequency normal modes in macromolecules", Biopolymers, vol.34, p759-771, where the RTB approximation is introduced (Scanned: 7 Mo).

Sanejouand, Y.H. (1990): "Etude theorique des mouvements internes de grande amplitude de la decaalanine et du fragment C-terminal de la proteine ribosomale L7/L12", Ph.D. thesis, Universite Paris Sud (Scanned: 97 Mo; in french).

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Nonlinear modes of proteins:

Piazza, F., & Sanejouand, Y.H. (2011): "Breather-mediated energy transfer in proteins", DCDS-S vol.4 (5), p1247-1266, where more details about the series of previous works are given. Most of our results can be reproduced with nnmdw.

Piazza, F., & Sanejouand, Y.H. (2009): "Energy transfer in nonlinear network models of proteins", EPL vol.88, 68001 ; arXiv 0905.1570, where some energy transfers in nonlinear network models of proteins are analyzed in depth.

Piazza, F., & Sanejouand, Y.H. (2009): "Long-range energy transfer in proteins", Phys. Biol. vol.6, 046014 ; arXiv 0908.2378, where it is shown that after a localized kick energy transfer can indeed occur, both efficiently and over large distances.

Piazza, F., & Sanejouand, Y.H. (2008): "Discrete breathers in protein structures", Phys. Biol. vol.5, 026001 ; arXiv 0802.3593, where the previous results are analyzed in depth, and compared to analytical solutions which suggest that energy can jump from a site to another. See also the comments of Peter Csermely in Nature (Journal Club) vol.454, p.5 (2008).

Juanico, B., Sanejouand, Y.H., Piazza, F., & De Los Rios, P. (2007): "Discrete breathers in nonlinear network models of proteins", Phys. Rev. letters, vol.99, 238104 ; arXiv 0706.1017, where it is shown that high amounts of energy may pop up in (or near) enzyme active sites, as a consequence of large and long-lived thermal fluctuations of nonlinear origin. See also the comments of Phil Schewe in Physics news update, issue 846(2), November 12 (2007), and of Mark Buchanan in New Scientist, issue 2637, January 5, p.8 (2008). Figure 1 can (almost) be reproduced with the demo script of nnmdw.

Piazza, F., De Los Rios, P., & Sanejouand, Y.H. (2005): "Slow energy relaxation of macromolecules and nanoclusters in solution", Phys. Rev. letters, vol.94, 145502 ; arXiv 0503436. The insets of Figure 2 can (almost) be reproduced with the demo script of nnmdw.

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Host-virus interactions:

Sanejouand, Y.H. (2017): "Mutational dynamics of influenza A viruses: a principal component analysis of hemagglutinin sequences of subtype H1", arXiv 1710.01594, DOI 10.5281/zenodo.2566385. This analysis shows that the 2009 pandemic was associated to a major change in the hydrophobicity pattern of hemagglutinin. It also highlights the high variability of viral sequences coming from swine.

Sanejouand, Y.H. (2017): "A singular mutation in the hemagglutinin of the 1918 pandemic virus", Archives of Biochemistry and Biophysics, vol.625, p13-16; arXiv 1610.04470). Gly 188 (H3 subtype numbering) was found in the 1918 hemagglutinin sequence (H1 subtype), rarely afterwards, and never again in sequences of human viruses of subtype H1.

Maekawa, A., Schmidt, B., Fasekas de St. Groth, B., Sanejouand, Y.H., & Hogg, P.J. (2006): "Evidence for a domain-swapped CD4 dimer as the co-receptor for binding to class II major histocompatibility complex", J. Immunol., vol.176, p6873-6878.

Sanejouand, Y.H. (2004): "Domain-swapping of CD4 upon dimerization", Proteins: Structure, Function and Bioinformatics vol.57(1), p205-212. PDB files of the proposed contact dimer and of the predicted domain-swapped form, where domain-swapping implies disulfide exchange, yielding disulfide-bonded dimers.

Sanejouand, Y.H. (1997) "Rôle du changement de conformation du CD4 lors de la fusion VIH/cellule", C.R. Acad. Sci., Sciences de la vie, vol.320, p163-170 (editor: Luc Montagnier). A check of previous results, starting from other cristallographic data, and a proposal for the underlying mechanism (in french, but with an extended english summary).

Sanejouand, Y.H. (1996): " Normal-mode analysis suggests important flexibility between the two N-terminal domains of CD4 and supports the hypothesis of a conformational change in CD4 upon HIV binding", Protein Engineering, vol.9, p671-676. (Scanned: 6 Mo)

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Sequence-structure relationship:

Sanejouand, Y.H. (2023): "Are most human specific proteins encoded by long non-coding RNAs ?". Under review. Submitted version: biorXiv 2023.11.09.566363. Where human proteins with no known homologue in a reference database of 27 proteomes of primates are considered. Among them, only 2 are known at the protein level and 23 at the transcript level. 21 of these 25 proteins are found encoded by an open reading frame of a long non-coding RNA, but a majority of them are predicted to be globular.

Sanejouand, Y.H. (2023): "On the unknown proteins of eukaryotic proteomes". Journal of Molecular Evolution, vol.91, p492-501. Submitted version: arXiv 2209.11001. Where proteins of 362 proteomes with no known homologue in a reference database of 36 proteomes as taxonomically diverse as possible have been considered, suggesting that unknown (possibly new, young, lineage-specific) proteins do not seem to accumulate in metazoan proteomes in the same way as in proteomes from other eukaryotic lineages.

Dhingra, S., Sowdhamini, R., Sanejouand, Y.H., Cadet, F. & Offmann, B. (2020): "Customised fragment libraries for ab initio protein structure prediction using a structural alphabet", arXiv 2005.01696.

Vetrivel, I., Mahajan, S., Tyagi, M., Hoffmann, L., Sanejouand, Y.H., Srinivasan, N., de Brevern, A.G., Cadet, F. & Offmann, B. (2017): "Knowledge-based prediction of protein backbone conformation using a structural alphabet", PLOS ONE, vol.12(11), e0186215, DOI 10.1371/journal.pone.0186215.

Mahajan, S., de Brevern, A.G., Sanejouand, Y.H., Srinivasan, N., & Offmann, B. (2015): "Use of a structural alphabet to find compatible folds for amino acid sequences", Protein Science, vol.24, p145-153, DOI 10.1002/pro.2581.

Sanejouand, Y.H., & Trinquier, G. (2003): "Proteinlike properties of simple models" , In Mathematical Methods for Protein Structure Analysis and Design, p147-153, C. Guerra & S. Istrail eds, Springer (Scanned: 2 Mo).

Sanejouand, Y.H., & Trinquier, G. (2000): "L'apport des modeles sur reseau cubique a l'etude des proprietes des proteines ", Bull. Soc. Fr. Phys. vol.125, p25-27 (Scanned: 3 Mo; in french).

Trinquier, G., & Sanejouand, Y.H. (1999): "New proteinlike properties of cubic lattice models.", Phys. Rev. E. vol.59(1), p942-946 .

Trinquier, G., & Sanejouand, Y.H. (1998) "Which effective property is best preserved by the genetic code ?", Protein Engineering, vol.11, p153-169 .

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Applications of standard methods:

Sanejouand, Y.H. (2022): "At least three xenon binding sites in the glycine binding domain of the N-methyl D-aspartate receptor", Archives of Biochemistry and Biophysics, vol.724, 109265. Submitted version: arXiv 2203.02219. Five MD docking simulations allowed to find three different binding sites for xenon, which induces anesthesia by inhibiting NMDA receptors. These three sites are next to each other, one of them being next to the glycine site. See the PDB file with the three sites occupied by xenon.

Teze, D., Zhao, J., Wiemann, M., Kazi, Z.G.A., Lupo, R., Zeuner, B., Vuillemin, M., Ronne, M.E., Carlstrom, G., Duus, J.O., Sanejouand, Y.H., O'Donohue, M.J, Karlsson, E.N., Faure, R., Stalbrand, H., & Svensson, B. (2021): "Rational Enzyme Design Without Structural Knowledge: A Sequence-Based Approach for Efficient Generation of Transglycosylases " Chemistry: a european journal, vol.27 (40), p10323-10334. Submitted version: ChemrXiv 11538708; the make_msa software used for sequence conservation analyzes. Mutating highly conserved residues also proved efficient in the case of enzymes from GH2, GH10, GH20, GH29 and GH51 families.

Hendrickx, J., Tran, V., Sanejouand, Y.H. (2020): "Numerous severely twisted N-acetylglucosamine conformations found in the protein databank", Proteins: Structure, Function and Genetics, vol.88 (10), p1376-1383 . Where it is noteworthy shown that there were numerous local errors in protein structures uploaded in the PDB between 2000 and 2015.

David, B., Arnaud, P., Tellier, C., & Sanejouand, Y.H. (2019): "Toward the design of efficient transglycosidases: the case of the GH1 of Thermus thermophilus" Protein Engineering, vol.32 (7), p309-316 , DOI 10.1093/protein/gzz032. Catalytically efficient mutants with high transglycosylation yields were obtained by mutating residues nearby the acid-base. Interestingly, while in the wild type the sidechain of the acid-base is only found able to sample a pair of equivalent conformations during 500 ns-long molecular dynamics simulations, its flexibility is found much higher in the case of the high transglycosylation yield mutants.

David, B., Irague, R., Jouanneau, D., Daligault, F., Czjzek, M., Sanejouand, Y.H. & Tellier, C. (2017): "Internal water dynamics control the transglycosylation/hydrolysis balance in the agarase (AgaD) of Zobellia galactanivorans" ACS Catalysis, vol.7, p3357-3367. In the case of this GH16 (GH-B clan, jelly roll fold), mutating residues flanking an internal water chain nearby the active site allowed to impair severely hydrolysis, without perturbing the transglycosylation activity.

Teze, D., Daligault, F., Ferriere, V., Sanejouand, Y.H. & Tellier, C. (2015): "Semi-rational approach for converting a GH36 alpha-glycosidase into an alpha-transglycosidase" Glycobiology, vol.25 (4), p420-427; HAL 01114459. Mutating highly conserved residues nearby the -1 site proved efficient in the case of a GH36 (GH-D clan, TIM-barrel fold).

Teze, D., Hendrickx, J., Czjzek, M., Ropartz, D., Sanejouand, Y.H., Tran, V. Tellier, C. & Dion, M. (2014): "Semi-rational approach for converting a GH1 beta-glycosidase into a beta-transglycosidase", Protein Engineering, vol.27 (1), p13-19, DOI 10.1093/protein/gzt057. Structures of two GH1 mutants with improved transglycosylation yields were obtained (PDB 3ZJK and 4BCE). No significant difference with the wild type (PDB 1UG6) could be noticed. On the other hand, other mutants with high transglycosylation yields were found, by mutating highly conserved residues nearby the -1 site.

Teze, D., Hendrickx, J., Dion, M., Tellier, C., Woods, V.L., Tran, V. & Sanejouand, Y.H. (2013): "Conserved water molecules in family 1 glycosidases: a DXMS and molecular dynamics study", Biochemistry, vol.52 (34), p5900-5910, DOI 10.1021/bi400260b. Experimental and simulation data in favor of the existence of several narrow (or intermittent) water channels in GH1 (GH-A clan, TIM barrel fold) were examined.

Chaput, L., Sanejouand, Y.H., Balloumi, A., Tran, V., & Graber, M. (2012): " Contribution of both catalytic constant and Michaelis constant to CALB enantioselectivity; use of FEP calculations for prediction studies ", J. Mol. Catal. B vol.76, p29-36 (PDF).

Tabrett, C., Harrison, C.F., Schmidt, B., Bellingham, S.A., Hardy, T., Sanejouand, Y.H., Hill, A.F., & Hogg, P.J. (2010): "Changing the solvent accessibility of the prion protein disulfide bond markedly influences its trafficking and effect on cell function", Biochem. J., vol.428(2), p169-182.

Gomes, E., Sagot, E., Gaillard, C., Laquitaine, L., Poinsot, B., Sanejouand, Y.H., Delrot, S., & Coutos-Thevenot, P. (2003): " Nonspecific Lipid-Transfer Protein Genes Expression in Grape (Vitis sp.) cells in Response to Fungal Elicitor Treatments.", M.P.M.I., vol.16, p456-464.

Willson, M., Sanejouand, Y.H., Perie, J., Hannaert, V., & Opperdoes, F. (2002): "Sequencing, Modelling, and Selective Inhibition of Trypanosoma brucei hexokinase.", Chemistry & Biology vol.9, p1-20.

Allouche, D., Parello, J., & Sanejouand, Y.H. (1999): "Ca/Mg exchange in parvalbumin and other EF-hand proteins. A theoretical study.", J. Mol. Biol. vol.285(2), p855-873.

Willson, M., Alric, I., Perie, J., & Sanejouand, Y.H. (1997): "Yeast hexokinase inhibitors designed from the 3-D enzyme structure rebuilding", J. Enzyme Inhibition vol.12, p101-127.

Fabiano, A.S., Allouche, D., Sanejouand, Y.H., Paillous, N. (1997): "Synthesis of a new cationic Pyropheophorbide derivative and studies of its aggregation process in aqueous solution", Photochemistry and Photobiology vol.66, p336-345.

Durup, J., Alary, F., & Sanejouand, Y.H. (1994): "Molecular dynamics simulation of an antigen-antibody complex: hydration structure and dissociation dynamics" in Statistical mechanics, protein structure and protein-substrate interactions, S. Doniach ed., Plenum Press, NY, p339.

Alary, F., Durup, J., & Sanejouand, Y.H. (1993): "Molecular dynamics study of the hydration structure of an antigen-antibody complex", J. Phys. Chem., vol.97, p13864-13876 (Scanned: 26 Mo). Two simulations, less than 100 ps each, were analyzed.

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Force field parametrization:

Periole, X., Allouche, D., Ramirez-Solis, A., Ortega-Blake, I, Daudey, J.-P., & Sanejouand, Y.H (1998): "New effective potentials extraction method for the interaction between cations and water.", J. Phys. Chem. B. vol.102, p8579-8587.

Periole, X., Allouche, D., Daudey, J.-P., & Sanejouand, Y.H. (1997) "Simple two-body cation-water interaction potentials derived from ab-initio calculations. Comparison to results obtained with an empirical approach", J. Phys. Chem. B, vol.101, p5018-5025.

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Other field:

Sanejouand, Y.H. (2023): "A robust assessment of the local anisotropy of the Hubble constant" Under review. Submitted versions: arXiv 2312.05896. Comments of first one (Qeios). Seven cosmological models are found to be not consistent with both low and high redshift supernovae of the Pantheon+ sample. When low-redshift supernovae are ignored, or when subsets of low-redshift supernovae roughly centered on the direction of the CMB dipole are considered, a pair of cosmological models become consistent with supernova data, namely, Lambda-CDM and the tired-light model proposed previously.

Sanejouand, Y.H. (2022): "A framework for the next generation of stationary cosmological models" Int. J. Mod, Phys. D, vol.31 (10), 2250084; submitted versions: arXiv 2005.07931. Another generic tired-light hypothesis that yields the same Hubble-like law, combined with the hypothesis that the Universe is far from being as transparent as assumed nowadays, yields distance-redshift relationships matching various observational data up to redshift two, at least.

Sanejouand, Y.H. (2019): "A loss of photons along the line-of-sight can explain the Hubble diagram for quasars", HAL 02190771, DOI 10.13140/RG.2.2.23497.29280. A new luminosity-distance is proposed, which allows to match the standard cosmic distance duality relation up to redshift 0.2.

Sanejouand, Y.H. (2019): "No obvious change in the number density of galaxies up to z=3.5", HAL 02019920, DOI 10.13140/RG.2.2.34513.99688. Previous results obtained with counts of long gamma-ray bursts are confirmed by the study of counts of galaxies in the Hubble Ultra Deep Field.

Sanejouand, Y.H. (2018): "Has the density of sources of gamma-ray bursts been constant over the last ten billion years ?", arXiv 1803.05303. A generic tired-light hypothesis yields the Hubble-like law advocated in the previous paper. The analysis of counts of long gamma-ray bursts suggests that the number density of galaxies has been nearly constant for a while.

Sanejouand, Y.H. (2014): "A simple Hubble-like law in lieu of dark energy", arXiv 1401.2919. Starting from a simple formula for the age-redshift relationship, it is shown that relaxing the Etherington cosmic distance duality relation provides a new way to get rid of the so-called "dark energy".

Sanejouand, Y.H. (2009): "About some possible empirical evidences in favor of a cosmological time variation of the speed of light", EPL vol.88, 59002 ; submitted version: arXiv 0908.0249. See also the comment in Optics and Photonics Focus vol.8, s.4 (2010), by Giovanni Volpe. With respect to the previous paper, a discussion of the Pioneer anomaly has been added.

Sanejouand, Y.H. (2005): "A simple varying-speed-of-light hypothesis is enough for explaining high-redshift supernovae data", arXiv 050958.

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(Reload several times to see the Erdre, nearby the University, in Nantes, the Rhone, in Lyon, the Dune du Pilat, near Arcachon, the Garonne, in Toulouse, a flower, in the Anjou countryside, or a view from the Boboli garden, in Firenze)