http://hdl.handle.net/2268/139 Search this channel search http://orbi.ulg.ac.be/simple-search http://hdl.handle.net/2268/148614 Title: Computers As Genomic Time Machines for Meeting our Ancestors <br/> <br/>Author, co-author: Baurain, Denis Thu, 16 May 2013 19:40:36 GMT http://hdl.handle.net/2268/148613 Title: The African coelacanth genome provides insights into tetrapod evolution. <br/> <br/>Author, co-author: Amemiya, Chris T.; Alfoldi, Jessica; Lee, Alison P.; Fan, Shaohua; Philippe, Herve; Maccallum, Iain; Braasch, Ingo; Manousaki, Tereza; Schneider, Igor; Rohner, Nicolas; Organ, Chris; Chalopin, Domitille; Smith, Jeramiah J.; Robinson, Mark; Dorrington, Rosemary A.; Gerdol, Marco; Aken, Bronwen; Biscotti, Maria Assunta; Barucca, Marco; Baurain, Denis; Berlin, Aaron M.; Blatch, Gregory L.; Buonocore, Francesco; Burmester, Thorsten; Campbell, Michael S.; Canapa, Adriana; Cannon, John P.; Christoffels, Alan; De Moro, Gianluca; Edkins, Adrienne L.; Fan, Lin; Fausto, Anna Maria; Feiner, Nathalie; Forconi, Mariko; Gamieldien, Junaid; Gnerre, Sante; Gnirke, Andreas; Goldstone, Jared V.; Haerty, Wilfried; Hahn, Mark E.; Hesse, Uljana; Hoffmann, Steve; Johnson, Jeremy; Karchner, Sibel I.; Kuraku, Shigehiro; Lara, Marcia; Levin, Joshua Z.; Litman, Gary W.; Mauceli, Evan; Miyake, Tsutomu; Mueller, M. Gail; Nelson, David R.; Nitsche, Anne; Olmo, Ettore; Ota, Tatsuya; Pallavicini, Alberto; Panji, Sumir; Picone, Barbara; Ponting, Chris P.; Prohaska, Sonja J.; Przybylski, Dariusz; Saha, Nil Ratan; Ravi, Vydianathan; Ribeiro, Filipe J.; Sauka-Spengler, Tatjana; Scapigliati, Giuseppe; Searle, Stephen M. J.; Sharpe, Ted; Simakov, Oleg; Stadler, Peter F.; Stegeman, John J.; Sumiyama, Kenta; Tabbaa, Diana; Tafer, Hakim; Turner-Maier, Jason; van Heusden, Peter; White, Simon; Williams, Louise; Yandell, Mark; Brinkmann, Henner; Volff, Jean-Nicolas; Tabin, Clifford J.; Shubin, Neil; Schartl, Manfred; Jaffe, David B.; Postlethwait, John H.; Venkatesh, Byrappa; Di Palma, Federica; Lander, Eric S.; Meyer, Axel; Lindblad-Toh, Kerstin <br/> <br/>Abstract: The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution. Thu, 16 May 2013 19:34:12 GMT http://hdl.handle.net/2268/148557 Title: Function, diversity and therapeutic potential of the N-terminal domain of human chemokine receptors <br/> <br/>Author, co-author: Szpakowska, Martyna; Fievez, Virginie; Arumugan, Karthik; van Nuland, Nico; Schmit, Jean-Claude; Chevigné, Andy Thu, 16 May 2013 09:43:41 GMT http://hdl.handle.net/2268/148470 Title: Complex regulation of the FRD3 gene in Arabidopsis relatives <br/> <br/>Author, co-author: Charlier, Jean-Benoit; Polese, Catherine; Nouet, Cécile; Krämer, Ute; Motte, Patrick; Hanikenne, Marc Tue, 14 May 2013 13:20:24 GMT http://hdl.handle.net/2268/148459 Title: Replacing explicit water and membrane molecules in molecular dynamics simulation to boost simulation speed <br/> <br/>Author, co-author: Steinhauer, Sven; Crowet, Jean-Marc; Lins, Laurence; Brasseur, Robert <br/> <br/>Abstract: Molecular dynamics (MD) is an appropriate method for investigation of biomolecular systems and helps in explaining results from wet lab experiments or in getting further insight into details, which are not accessible by experimental methods(Lindahl, 2008). By now, many biologically relevant processes for drug design, toxicological studies and other fields of application, can not be performed by atomistic MD simulations (Lindahl, 2008). In MD, the necessary time effort for carrying out a simulation is considerable and depends mainly on (1) the complexity of the simulated system (2) the simulated time scale (3) the simulation method (4) the efficiency of used hardware and software algorithms. Carried out MD simulations nowadays may still take weeks of calculation on high end computers. In practice, biologically relevant processes, as e.g. protein folding, take usually place above the time scale of milli seconds. They can take up to the order of some thousands of seconds (in case of the folding of membrane proteins). Molecular dynamics computer simulations have reached the scale of micro seconds for simulations of systems where each atom was described and simulated over time.(Lindahl, 2008) Nevertheless, MD has risen to an important promoter methodology for many different fields of application. By replacing bunches of atoms by artificial particles, complexity of the systems can be reduced. This method is called the coarse grain method (CG). Biggin and Bond (2008) found an acceleration of their simulation processes for self assembling membrane / protein systems in water by factor 100. They estimated one to two days of calculation for a simulated time scale of 0.1 to 0.2 micro seconds for their systems. Implicit force fields like "IMPALA", aim to describe water and/or membrane molecules in simulations by a couple of simple and partially precalculable equations. “IMPALA” is a force field initially developed by our laboratory. Using this method, thousands of water and lipid molecules can be replaced, leading to a reduced complexity of the system to be simulated. "IMPALA"(Ducarme et al., 1998) based on the assumption of rigid peptides and aimed to find the insertion characteristics of such in membranes. Elimination of the necessity for simulating the aqueous and lipid phase atom by atom in the software package "Gromacs"(Berendsen et al., 1995) will permit both: a gain of speed, as it was already the case for the introduction of the coarse grain method, and a gain of precision by turning rigid molecules flexible through "Gromacs". Our current work is the integration of the "IMPALA" implicit force field into "Gromacs". Biggin, P.C. & Bond, P.J. Molecular dynamics simulations of membrane proteins. Methods Mol. Biol. 443, 147-60(2008). Berendsen, et al. (1995) Comp. Phys. Comm. 91: 43-56. Ducarme, P., Rahman, M. & Brasseur, R. IMPALA: a simple restraint field to simulate the biological membrane in molecular structure studies. Proteins 30, 357-71(1998). Lindahl, E.R. (2008). Molecular dynamics simulations. Methods Mol. Biol. 443, 3-23. Tue, 14 May 2013 12:12:29 GMT http://hdl.handle.net/2268/148443 Title: MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy. <br/> <br/>Author, co-author: Halkein, Julie; Tabruyn, Sebastien P.; Ricke-Hoch, Melanie; Haghikia, Arash; Nguyen, Ngoc-Quynh-Nhu; Scherr, Michaela; Castermans, Karolien; Malvaux, Ludovic; Lambert, Vincent; Thiry, Marc; Sliwa, Karen; Noël, Agnès; Martial, Joseph; Hilfiker-Kleiner, Denise; Struman, Ingrid <br/> <br/>Abstract: Peripartum cardiomyopathy (PPCM) is a life-threatening pregnancy-associated cardiomyopathy in previously healthy women. Although PPCM is driven in part by the 16-kDa N-terminal prolactin fragment (16K PRL), the underlying molecular mechanisms are poorly understood. We found that 16K PRL induced microRNA-146a (miR-146a) expression in ECs, which attenuated angiogenesis through downregulation of NRAS. 16K PRL stimulated the release of miR-146a-loaded exosomes from ECs. The exosomes were absorbed by cardiomyocytes, increasing miR-146a levels, which resulted in a subsequent decrease in metabolic activity and decreased expression of Erbb4, Notch1, and Irak1. Mice with cardiomyocyte-restricted Stat3 knockout (CKO mice) exhibited a PPCM-like phenotype and displayed increased cardiac miR-146a expression with coincident downregulation of Erbb4, Nras, Notch1, and Irak1. Blocking miR-146a with locked nucleic acids or antago-miRs attenuated PPCM in CKO mice without interrupting full-length prolactin signaling, as indicated by normal nursing activities. Finally, miR-146a was elevated in the plasma and hearts of PPCM patients, but not in patients with dilated cardiomyopathy. These results demonstrate that miR-146a is a downstream-mediator of 16K PRL that could potentially serve as a biomarker and therapeutic target for PPCM. Tue, 14 May 2013 09:31:00 GMT http://hdl.handle.net/2268/148434 Title: Adavances in proteomics for the FP7 Venomics project <br/> <br/>Author, co-author: Degueldre, Michel; Quinton, Loïc; De Pauw, Edwin Tue, 14 May 2013 08:26:35 GMT http://hdl.handle.net/2268/148096 Title: Identification et caractérisation des sous-unités ELP5 et ELP6 du complexe Elongator humain <br/> <br/>Author, co-author: Gillard, Magali <br/> <br/>Abstract: Familial Dysautonomia is a neurodegenerative disorder that affects the autonomic and sensory nervous systems. This disease results from loss-of-function mutations of the ELP1-encoding gene. ELP1 is required for the integrity of the so-called Elongator complex, which is composed of two sub-proteins complexes, namely the core-Elongator (ELP1 to ELP3) and HAP (ELP4 to ELP6). While ELP3 is acting as an acetyltransferase that target multiple substrates such as nuclear histones and cytoplasmic α-tubulin, the ELP4-6 has been recently described as an ATPase. This complex has been initially identified as a component of a hyperphosphorylated RNA polymerase II holoenzyme. As a result, Elongator is involved in transcriptional elongation. Since, other roles have been assigned. Elongator is indeed also required for some tRNA modifications in the cytoplasm and consequently controls translation fidelity. Those molecular functions underlie the capacity of Elongator to regulate cell division, DNA-damage response and cell motility. It is likely that a better understanding of the molecular functions of Elongator will clarify its role in these cellular processes and probably highlight new features. The identity of human ELP1 through ELP4 has been reported but human ELP5 and ELP6 have remained uncharacterized. We therefore initiated a study dedicated to the identification and characterization of both proteins. A biochemical purification of ELP4 was conducted to isolate all associated proteins. Such experimental approach led to the identification of DERP6 and C3ORF75 as human ELP5 and ELP6 subunits of the Elongator complex, respectively. We further investigated the cellular functions of both subunits by combining biochemical analysis and cellular assays. Our results show that DERP6/Elp5 is required for the integrity and the fucntion of Elongator and directly connects ELP3 to ELP4. Our laboratory has previously demonstrated the key role of Elongator in cell migration. As cell motility is required for cell invasion and metastasis, we therefore investigated to which extent Elongator is involved in those processes. The migration and tumorigenicity of melanoma-derived cells are significantly decreased upon Elongator invalidation through Elp1 or Elp3 depletion. Strikingly, DERP6/Elp5 and C3ORF75/Elp6-depleted melanoma cells have similar defects, further supporting the idea that DERP6/Elp5 and C3ORF75/Elp6 are essential for Elongator function. Together, our data identify DERP6/ELP5 and C3ORF75/ELP6 as key players for migration, invasion and tumorigenicity of melanoma cells, as integral subunits of Elongator.; La dysautonomie familiale est une pathologie neurodégénérative qui touche les systèmes nerveux sensoriel et autonome. Cette maladie résulte de mutations de perte de fonction du gène codant pour la protéine ELP1. Celle-ci permet l’assemblage d’Elongator, un complexe doué d’une activité acétyltransférase et composé de six sous-unités réparties en deux sous-complexes protéiques : d’une part le « core-Elongator » (ELP1 à ELP3) et d’autre part le complexe HAP (ELP4 à ELP6). Alors que la sous-unité ELP3 est capable d’acétyler de nombreux substrats dont les histones nucléaires et la tubuline-α cytoplasmique, une activité ATPase a récemment été identifiée dans le complexe ELP4-6. Initialement identifié sur base de son association à l’ARN polymérase II, Elongator a depuis été caractérisé comme un acteur important de l’acétylation des microtubules, de même que comme complexe requis pour certaines modifications des ARNs de transfert. Ces fonctions moléculaires très diverses lui confèrent la capacité de réguler de nombreux processus physiologiques tels que la division ou la migration cellulaire. Une meilleure connaissance des fonctions moléculaires d’Elongator permettrait non seulement d’éclaircir son rôle dans ces différents processus cellulaires mais également de révéler de nouvelles fonctions. Au moment d’entamer nos travaux, l’identité des sous-unités humaines ELP1, 2, 3 et 4 était connue, à l’inverse des sous-unités ELP5 et ELP6. Nous avons donc entrepris d’identifier et de caractériser ces deux protéines. La purification de la protéine ELP4 humaine nous a permis d’isoler le complexe Elongator dans son intégralité. Ainsi, nous avons pu identifier les protéines DERP6 et C3ORF75 comme étant respectivement les sous-unités ELP5 et ELP6 du complexe Elongator humain. Nous avons en outre démontré qu’ELP5 est indispensable pour permettre l’association entre ELP3 et à ELP4, ceci suggérant qu’ELP5 est également requis pour l’intégrité et la fonction d’Elongator. Notre laboratoire a précédemment mis en évidence l’importance d’Elongator dans la migration cellulaire. Compte-tenu du fait que la migration est une étape critique dans l’acquisition du pouvoir invasif et métastatique des cellules cancéreuses, nous avons voulu déterminer dans quelle mesure Elongator intervenait dans ces processus physiopathologiques en étudiant une lignée dérivée de mélanome murin à titre de modèle expérimental. La perte de fonction d’Elongator altère la mobilité de ces cellules de même que leur capacité à former des colonies en agar mou. Les mêmes résultats ont été obtenus en invalidant les sous-unités Elp5 et Elp6 nouvellement identifiées dans ces cellules murines. L’ensemble de nos résultats montre qu’Elongator est requis pour la migration et la tumorigénicité des cellules cancéreuses issues de mélanome murin et que les sous-unités DERP6/ELP5 et C3ORF75/ELP6 confèrent ces propriétés cellulaires en tant que sous-unités de ce complexe. Thu, 09 May 2013 09:45:12 GMT http://hdl.handle.net/2268/148083 Title: Replacing explicit water and lipids by implicit representation in molecular dynamics simulations <br/> <br/>Author, co-author: Steinhauer, Sven; Crowet, Jean-Marc; Lins, Laurence; Brasseur, Robert <br/> <br/>Abstract: Molecular dynamics (MD) is an appropriate method for investigation of biomolecular systems and helps in explaining results from wet lab experiments or in getting further insight into details, which are not accessible by experimental methods(Lindahl, 2008). By now, many biologically relevant processes for drug design, toxicological studies and other fields of application, can not be performed by atomistic MD simulations (Lindahl, 2008). <br />In MD, the necessary time effort for carrying out a simulation is considerable and depends mainly on (1) the complexity of the simulated system (2) the simulated time scale (3) the simulation method (4) the efficiency of used hardware and software algorithms. Carried out MD simulations nowadays may still take weeks of calculation on high end computers. <br /> <br />In practice, biologically relevant processes, as e.g. protein folding, take usually place above the time scale of milli seconds. They can take up to the order of some thousands of seconds (in case of the folding of membrane proteins). Molecular dynamics computer simulations have reached the scale of micro seconds for simulations of systems where each atom was described and simulated over time.(Lindahl, 2008) <br /> <br />Nevertheless, MD has risen to an important promoter methodology for many different fields of application. By replacing bunches of atoms by artificial particles, complexity of the systems can be reduced. This method is called the coarse grain method (CG). Biggin and Bond (2008) found an acceleration of their simulation processes for self assembling membrane / protein systems in water by factor 100. They estimated one to two days of calculation for a simulated time scale of 0.1 to 0.2 micro seconds for their systems. <br /> <br />Implicit force fields like "IMPALA", aim to describe water and/or membrane molecules in simulations by a couple of simple and partially precalculable equations. “IMPALA” is a force field initially developed by our laboratory. Using this method, thousands of water and lipid molecules can be replaced, leading to a reduced complexity of the system to be simulated. <br />"IMPALA"(Ducarme et al., 1998) based on the assumption of rigid peptides and aimed to find the insertion characteristics of such in membranes. Elimination of the necessity for simulating the aqueous and lipid phase atom by atom in the software package "Gromacs"(Berendsen et al., 1995) will permit both: a gain of speed, as it was already the case for the introduction of the coarse grain method, and a gain of precision by turning rigid molecules flexible through "Gromacs". Our current work is the integration of the "IMPALA" implicit force field into "Gromacs". <br /> <br />Biggin, P.C. & Bond, P.J. Molecular dynamics simulations of membrane proteins. Methods Mol. Biol. 443, 147-60(2008). <br />Berendsen, et al. (1995) Comp. Phys. Comm. 91: 43-56. <br />Ducarme, P., Rahman, M. & Brasseur, R. IMPALA: a simple restraint field to simulate the biological membrane in molecular structure studies. Proteins 30, 357-71(1998). <br />Lindahl, E.R. (2008). Molecular dynamics simulations. Methods Mol. Biol. 443, 3-23. Wed, 08 May 2013 12:29:25 GMT http://hdl.handle.net/2268/147961 Title: Study of the structural factors that modulate the metal binding affinity of the Arabidopsis halleri HMA4 <br/> <br/>Author, co-author: Laurent, Clémentine; Hanikenne, Marc; Galleni, Moreno Mon, 06 May 2013 13:50:21 GMT http://hdl.handle.net/2268/147960 Title: Study of the structural factors that modulate the metal binding affinity of the N-terminal domain of the Arabidospsis halleri HMA4 <br/> <br/>Author, co-author: Laurent, Clémentine; Damblon, Christian; Hanikenne, Marc; Galleni, Moreno Mon, 06 May 2013 13:46:52 GMT http://hdl.handle.net/2268/147893 Title: MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines. <br/> <br/>Author, co-author: Grosso, S.; Doyen, J.; Parks, S. K.; Bertero, T.; Paye, Alexandra; Cardinaud, B.; Gounon, P.; Lacas-Gervais, S.; Noël, Agnès; Pouyssegur, J.; Barbry, P.; Mazure, N. M.; Mari, B. <br/> <br/>Abstract: The resistance of hypoxic cells to radiotherapy and chemotherapy is a major problem in the treatment of cancer. Recently, an additional mode of hypoxia-inducible factor (HIF)-dependent transcriptional regulation, involving modulation of a specific set of micro RNAs (miRNAs), including miR-210, has emerged. We have recently shown that HIF-1 induction of miR-210 also stabilizes HIF-1 through a positive regulatory loop. Therefore, we hypothesized that by stabilizing HIF-1 in normoxia, miR-210 may protect cancer cells from radiation. We developed a non-small cell lung carcinoma (NSCLC)-derived cell line (A549) stably expressing miR-210 (pmiR-210) or a control miRNA (pmiR-Ctl). The miR-210-expressing cells showed a significant stabilization of HIF-1 associated with mitochondrial defects and a glycolytic phenotype. Cells were subjected to radiation levels ranging from 0 to 10 Gy in normoxia and hypoxia. Cells expressing miR-210 in normoxia had the same level of radioresistance as control cells in hypoxia. Under hypoxia, pmiR-210 cells showed a low mortality rate owing to a decrease in apoptosis, with an ability to grow even at 10 Gy. This miR-210 phenotype was reproduced in another NSCLC cell line (H1975) and in HeLa cells. We have established that radioresistance was independent of p53 and cell cycle status. In addition, we have shown that genomic double-strand breaks (DSBs) foci disappear faster in pmiR-210 than in pmiR-Ctl cells, suggesting that miR-210 expression promotes a more efficient DSB repair. Finally, HIF-1 invalidation in pmiR-210 cells removed the radioresistant phenotype, showing that this mechanism is dependent on HIF-1. In conclusion, miR-210 appears to be a component of the radioresistance of hypoxic cancer cells. Given the high stability of most miRNAs, this advantage could be used by tumor cells in conditions where reoxygenation has occurred and suggests that strategies targeting miR-210 could enhance tumor radiosensitization. Sat, 04 May 2013 03:00:07 GMT http://hdl.handle.net/2268/147886 Title: Recherches de lignées aromatiques d'Abies par hybridation somatique <br/> <br/>Author, co-author: Wathelet, Jean-Paul; Fauconnier, Marie-Laure; Michels, Franck; Misson, Jean-Pierre Fri, 03 May 2013 14:42:24 GMT http://hdl.handle.net/2268/147875 Title: Knock-down of the COX3 and COX17 gene expression of cytochrome c oxidase in the unicellular green alga Chlamydomonas reinhardtii <br/> <br/>Author, co-author: Remacle, Claire; Coosemans, Nadine; Jans, Frédéric; Hanikenne, Marc; Motte, Patrick; Cardol, Pierre <br/> <br/>Abstract: The COX3 gene encodes a core subunit of mitochondrial cytochrome c oxidase (complex IV) whereas the COX17 gene encodes a chaperone delivering copper to the enzyme. Mutants of these two genes were isolated by RNA interference in the microalga Chlamydomonas. The COX3 mRNA was completely lacking in the cox3-RNAi mutant and no activity and assembly of complex IV were detected. The cox17-RNAi mutant presented a reduced level of COX17 mRNA, a reduced activity of the cytochrome c oxidase but no modification of its amount. The cox3-RNAi mutant had only 40% of the wild-type rate of dark respiration which was cyanide-insensitive. The mutant presented a 60% decrease of H2O2 production in the dark compared to wild type, which probably accounts for a reduced electron leakage by respiratory complexes III and IV. In contrast, the cox17-RNAi mutant showed no modification of respiration and of H2O2 production in the dark but a two to threefold increase of H2O2 in the light compared to wild type and the cox3-RNAi mutant. The cox17-RNAi mutant was more sensitive to cadmium than the wild-type and cox3-RNAi strains. This suggested that besides its role in complex IV assembly, Cox17 could have additional functions in the cell such as metal detoxification or Reactive Oxygen Species protection or signaling. Concerning Cox3, its role in Chlamydomonas complex IV is similar to that of other eukaryotes although this subunit is encoded in the nuclear genome in the alga contrary to the situation found in all other organisms. Fri, 03 May 2013 11:50:43 GMT http://hdl.handle.net/2268/147870 Title: A type II NAD(P)H dehydrogenase mediates light-independent plastoquinone reduction in the chloroplast of Chlamydomonas. <br/> <br/>Author, co-author: Jans, Frédéric; Mignolet, Emmanuel; Houyoux, Pierre-Alain; Cardol, Pierre; Ghysels, Bart; Cuiné, S; Cournac, L; Peltier, G; Remacle, Claire; Franck, Fabrice <br/> <br/>Abstract: In photosynthetic eukaryotes, nonphotochemical plastoquinone (PQ) reduction is important for the regulation of photosynthetic electron flow. In green microalgae where this process has been demonstrated, the chloroplastic enzyme that catalyses nonphotochemical PQ reduction has not been identified yet. Here, we show by an RNA interference (RNAi) approach that the NDA2 gene, belonging to a type II NAD(P)H dehydrogenases family in the green microalga Chlamydomonas reinhardtii, encodes a chloroplastic dehydrogenase that functions to reduce PQ nonphotochemically in this alga. Using a specific antibody, we show that the Nda2 protein is localized in chloroplasts of wild-type cells and is absent in two Nda2-RNAi cell lines. In both mutant cell lines, nonphotochemical PQ reduction is severely affected, as indicated by altered chlorophyll fluorescence transients after saturating illumination. Compared with wild type, change in light excitation distribution between photosystems ('state transition') upon inhibition of mitochondrial electron transport is strongly impaired in transformed cells because of inefficient PQ reduction. Furthermore, the amount of hydrogen produced by Nda2-RNAi cells under sulfur deprivation is substantially decreased compared with wild type, which supports previous assumptions that endogenous substrates serve as source of electrons for hydrogen formation. These results demonstrate the importance of Nda2 for nonphotochemical PQ reduction and associated processes in C. reinhardtii. Fri, 03 May 2013 10:23:30 GMT http://hdl.handle.net/2268/147800 Title: The transcription factor Egr1 in zebrafish cartilage development <br/> <br/>Author, co-author: Dalcq, Julia <br/> <br/>Abstract: The cartilaginous elements forming the pharyngeal arches of the zebrafish derive from cranial neural crest cells. Their proper differentiation and patterning are regulated by reciprocal interactions between neural crest cells and surrounding endodermal, ectodermal and mesodermal tissues. In this study, we show that the endodermal factors Runx3 and Sox9b form a regulatory cascade with Egr1 resulting in transcriptional repression of the fsta gene, encoding a BMP antagonist, in pharyngeal endoderm. Using a transgenic line expressing a dominant negative BMP receptor or a specific BMP inhibitor (dorsomorphin), we show that BMP signaling is indeed required around 30 hpf in the neural crest cells to allow cell differentiation and proper pharyngeal cartilage formation. Runx3, Egr1, Sox9b and BMP signaling are required for expression of runx2b, one of the key regulators of cranial cartilage maturation and bone formation. Finally, we show that egr1 depletion leads to increased expression of fsta and inhibition of BMP signaling in the pharyngeal region. In conclusion, we show that the successive induction of the transcription factors Runx3, Egr1 and Sox9b constitutes a regulatory cascade that controls expression of Follistatin A in pharyngeal endoderm, the latter modulating BMP signaling in developing cranial cartilage in zebrafish. Thu, 02 May 2013 11:56:39 GMT http://hdl.handle.net/2268/147659 Title: Bolaamphiphiles Derived from Alkenyl L-rhamnosides and Alkenyl D-xylosides: Importance of the Hydrophilic Head <br/> <br/>Author, co-author: Gatard, Sylvain; Nasir, Mehmet Nail; Deleu, Magali; Legrand, Vincent; Bouquillon, Sandrine <br/> <br/>Abstract: The two step synthesis of a new bolaamphiphile derived from alkenyl L-rhamnosides was described. The general synthetic strategy of bolaamphiphiles derived from L-rhamnose was based on a previous work describing the synthesis of bolaamphiphiles derived from D-xylose. The conformational properties of this new compound were investigated by FTIR spectroscopy in an aqueous film in order to obtain a reference for further studies about the membrane-interacting properties. Moreover, the surface activity of this new bolaamphiphile was analyzed by Langmuir balance technology and was compared with that of the analogous bolaamphiphile derived from alkenyl D-xylosides. The findings indicate that the rhamnoside-based bolaform has an increased surface activity and a better ability to form aggregates than xyloside-based one. Mon, 29 Apr 2013 14:05:50 GMT http://hdl.handle.net/2268/147589 Title: Influence of the 524-VAAEIL-529 sequence of annexins A6 in their interfacial behavior and interaction with lipid monolayers. <br/> <br/>Author, co-author: Domon, Magdalena; Nasir, Mehmet Nail; Pikula, Slawomir; Besson, Françoise <br/> <br/>Abstract: Annexin A6 (AnxA6), a calcium- and membrane-binding protein, is expressed in mammalian cells in two isoforms: AnxA6-1 and AnxA6-2, the latter lacking the 524- VAAEIL-529 sequence at the start of repeat 7. The different intracellular localization of these two isoforms suggests distinct function in membrane dynamics. The aim of this work was to analyze the behavior of AnxA6 isoforms at the air/water interface alone and in the presence of membrane mimicking lipid monolayers. Using Langmuir technique showed that AnxA6-2 was less adsorbed to the neat air-water interface than AnxA6-1 at acidic pH and minor differences in their PM-IRRAS spectra were observed. Both isoforms exhibited similar behavior towards cholesterol monolayer. However, the interactions of AnxA6-2 with cholesterol ester monolayer were most favorable compared to AnxA6-1. Our experimental data are discussed in relation with the different intracellular localization of the two isoforms and with our constructed model of AnxA6-2 with the known crystal structure of AnxA6-1 showing the persistence of the 516-529 α- helix in AnxA6-2 despite the absence of the 524-VAAEIL-529 sequence. Mon, 29 Apr 2013 11:54:39 GMT http://hdl.handle.net/2268/147255 Title: Structural and functional study of the Arabidopsis halleri HMA4 N-terminal domain <br/> <br/>Author, co-author: Lekeux, Gilles; Laurent, Clémentine; Damblon, Christian; Hanikenne, Marc; Galleni, Moreno Tue, 23 Apr 2013 12:13:36 GMT http://hdl.handle.net/2268/147253 Title: Interactions of iturinic antibiotics with plasma membrane. Contribution of biomimetic membranes. <br/> <br/>Author, co-author: Nasir, Mehmet Nail; Besson, Françoise; Deleu, Magali <br/> <br/>Abstract: Iturinic antibiotics are produced by Bacillus subtilis strains and constitute a family including iturin A, mycosubtilin and bacillomycins D, F and Lc. They are cyclic lipopeptides having -amino fatty acids linked up to a peptide constituted by seven -aminoacids with an invariable LDDLLDL chiral sequence. The first three -aminoacids containing the tyrosyl residue are the same for all members. They are well-known by their strong antifungal activities but they have also antibacterial and hemolytic properties. These biological properties are due to their amphiphilic nature allowing interactions with different membrane components. Sterols found in plasma membranes are the privileged interaction partners of these lipopeptides. Moreover, the tyrosyl residue of the iturinic antibiotics seems to play an important role during their fixation to the plasma membrane, the result of which is often the cellular lysis. Within plasma membranes, there are particular regions with high sterol content. These microdomains have a different composition compared to the rest of the membrane; they are enriched in certain lipids and proteins and they are involved in many key cellular processes. Their perturbation could then have an important impact on the cell. Due to their composition, these microdomains could constitute the preferential target of iturin antibiotics. This review aims to synthetize the works related to the biological activities of iturinic antibiotics and focusses especially to their understanding at the molecular level with a discussion on the key chemical groups of the iturin antibiotics and on the potentiality of microdomains to constitute a target for these molecules Tue, 23 Apr 2013 12:07:28 GMT