Rgulations on seeds and varieties established 80 years ago proved to be to be efficient for European agriculture. Genetic progress for many traits, such as yield resistance to pests and diseases, have been observed for all cultivated crops. Plant variety protection by the UPOV (Union Internationale pour la Protetion Végétable) sytem came into being with the adoption of the International Convention for the Protection of New Varieties of Plants by a diplomatic conference in Paris on December 2, 1961. At this point the rights of plant breeders were recognized on an international basis. The UPOV Convention provides a sui generis form of intellectual property protection which has been specifically adapted for the process of plant breeding and has been developed with the aim of encouraging breeders to develop new varieties of plants. In contrast, the European GM regulation is very difficult to apply, very expensive and limits the development of biotechnology in Europe, as well for research as for development.
Transgenic plant varieties are grown since 1996 on surfaces increasing each year. They covered 114 million hectares worldwide in 2007, which shows their success among the farmers in developed as well as developing countries, despite the propaganda campaigns of the environmental movements and advocates of decline. The first transgenic crops (soybean, corn, coton and rapeseed) offer benefits in terms of health, economy and environment. Europe and especially France, which reject this technology, sentence their research to death and penalize their agriculture.
In this presentation, we review the complexity of the different biological events which occur during life cell cycles. Indeed transgenesis is not an unknown event for cells. In the second part of this article, the complex and complete evaluation process destined to assure the food safety of GMOs, before they are released on the market, is describd. Some ansers to questions frequently asked about the GMOs are given. It is concludedthat GMOs are probably more safe than their conventional non-GM counterpart.
The first transgenic animals, mice, were obtained in 1980. The techniques of gene transfer had to be adapted to obtain transgenic animals with an acceptable yield in about fifteen species. When the yield is low (low rate of random integration and targeted integration via homologous recombination), genetic modifications must be achieved in intermediate cells able to participate to the development of chimeric transgenic animals (ES cells, EG cells, iPS obtained by the dedifferentiation of somatic cells) or in somatic cells used as nuclear donor to generate transgenic clones. Various tools make possible a marked increase of homologous recombination efficiency (meganucleases and ZFN), or a gene inactivation at the genome level (direct or conditional knock out) or at the mRNA level (interfering RNAs). Vectors allow a more reliable transgene expression. Genetically modified animals are used mainly to obtain information on biological functions and human diseases. Transgenic animals produce recombinant pharmaceutical proteins in milk and soon in egg white. Pig organs adapted to be tolerated by patients might be tested in humans in five years. The projects based on the use of transgenesis to improve animal production are presently few. Transgenic salmon with accelerated growth might be on the market when their possible escape in oceans will be controlled.
The renin-angiotensin system (RAS) is one of the most important systems in physiology and in pathology. The (pro)renin receptor [(P)RR] is a new component of the system that has attracted much attention, being potentially a new therapeutic target, because the binding of renin and of prorenin triggers the activation of the mitogen-activated protein kinase p42/p44 followed by up-regulation of the expression of profibrotic genes. and because prorenin bound to (P)RR becomes catalytically active. The introduction of a renin inhibitor in the treatment of hypertension and of organ damages, together with the discovery of (P)RR, has revived the interest for the RAS and for potential new RAS blockers, in order to optimize RAS blockade in tissues.
Angiotensin II AT1 receptor is a G protein coupled receptor, which transduces the physiological effects (vasoconstriction, aldosterone secretion) f this vasoactive peptide. On an evolutionary point of view, this receptor has appeared early in the development of vertebrates, since it is present in cartilagenous fish. It has been duplicated in rodents without any consequence on its functions. It is unlikely that the angiotensin AT2 receptor, whose functions are still debated, has diverged from a common ancestral angiotensin receptor with the AT1 receptor. Numerous activating or inactivating point mutations have been identified by site-directed mutagenesis of the AT1 receptor sequence. However, such natural mutations do not appear to be frequent in the genesis of human diseases or in the diversity of phenotypic traits.
Autosomal recessive renal tubular dysgenesis (RTD) is a clinical disorder observed in fetuses, characterized by absence or poor development of proximal tubules and early onset and persistent oligohydramnios leading to the Potter sequence, associated with skull ossification defect. The disease is uniformly severe resulting in low blood pressure and perinatal death in most cases or in chronic renal disease in the few surviving patients. Based on the phenotype and the finding of striking changes in renal renin expression (absent or massive), we hypothesized and demonstrated that genetic defects in the renin-angiotensin system (RAS) components are the underlying causes of the disease. At the present time, molecular screening has been performed in 46 families (F) and homozygous or compound heterozygous mutations have been detected in 41. They affect the genes encoding renine (9F), angiotensinogen (3F), AT1 receptor (3F) and angiotensin converting enzyme (26F). These findings highlight the importance of the RAS during human kidney development. Moreover, the identification of the disease based on precise histological and immunohistological analysis, and the research of the genetic defect, now allow genetic counseling and early prenatal diagnosis.
The Angiotensin-Converting Enzyme (ACE) is crucial for vascular homeostasis in mammals. Three isoforms are present in the human. the somatic ACE (sACE) generates the vasoactive angiotensin II. The testicular isoform (tACE) is required for male fertility. ACE2 was cloned from another gene and displays an antagonistic role. Several ACEs were cloned from insects, despite their lack of a closed circulatory system. Insect isoforms are implied in reproduction and development. No sequence in the C. elegans genome is able to encode a functional enzyme. Nevertheless, an active ACE was characterized in an even more distant organism, the leech, in which the enzyme is mainly expressed within the digestive tract. The presence of ACE is lophotrochozoans raises questions about the appearance and original functions of the enzyme. Besides, the recent availability of genomic data unraveled the putative presence of orthologues in even more distant phyla such as cnidaria, placozoa and even many procaryotes. Moreover, the characterization of an active ACE in a proteobacteria indicates that the ancestor isoform was already functional. Thus, ACE is present from bacteria to mammals and exhibits incredibly conserved molecular, biochemical as well as structural features. The absence of ACE in all eucaryotic bicounts could thus result from a secondary loss. Taken together, these data suggest that ACE appeared early during the course of evolution. Mammalian ACE features could thus be a result of the long evolutive specialization of an ancient protease whose physiological functions remain to be elucidated.
The GABA(B) receptors belong to the family of class C metabotropic receptors. They are inhibitory receptors forming obligatory heterodimers. Their analgesic role in the dorsal horn of the spinal cord is well established since more than 25 years ago. However, Baclofen, the reference agonist of the GABA(B) receptor, proved to have little efficiency in clinics in neuropathic patients. It seems therefore useful to decipher GABA(B) functions in the nociceptive circuitry, and their regulation in conditions of chronic pain. In the present review, we will focus first on the distribution of the GABA(B) subtypes. Then, we will consider their pre- and post-synaptic functions in the dorsal horn of naïve rats. Finally, we will document the mechanisms that may lead to receptor impairment in neuropathic conditions.
La Societe de Biologie a ete le theâtre de nombreuses polemiques au sujet du mode d'action du curare pendant plus de trente annees. Apres une periode de mise au point technique des protocoles d'empoisonnement sur divers animaux, a laquelle contribuent Claude Bernard, Vulpian et leurs collegues, succede une autre, ou l'electrophysiologie allemande entre en scene, se combine avec les nouvelles donnees histologiques sur les plaques motrices, pour soutenir les vues de physiologistes plus jeunes qui s'affrontent a Claude Bernard et finissent par le convaincre. Selon eux, Vulpian en premier lieu, le curare abolit la transmission entre la plaque motrice et le muscle. Cette premiere ebauche d'une theorie de la neurotransmission nous aide a comprendre comment une nouvelle physiologie se met en place dans le sillage de l'ecole bernardienne par une meilleure integration des disciplines, une foi plus grande accordee au reductionnisme et au materialisme.
L'Enzyme de Conversion de l'Angiotensine (ECA) est cruciale dans l'homeostasie vasculaire des Mammiferes. Chez l'Homme, trois ECAs co-existent. L'ECA somatique (ECAso) produit l'angiotensine II vasoactive. L'ECA testiculaire (ECAt), est indispensable a la fertilite. L'ECA2, codee par un autre gene, possede un role antagoniste a celui de l'ECAso. Plusieurs ECAs ont ete clonees chez les Insectes, pourtant depourvus de systeme circulatoire ferme. Ces enzymes sont impliquees dans le developpement et la reproduction. Bien qu'aucune sequence du genome de Caenorhabditis elegans ne code pour une ECA fonctionnelle, une enzyme active est neanmoins presente chez un organisme encore plus distant, la sangsue. Cette enzyme est majoritairement exprimee dans le tractus digestif. Sa presence chez les Lophotrochozoaires pose les questions de l'apparition de l'ECA et de ses fonctions originelles. En outre, l'apport recent de nombreuses donnees genomiques a revele la presence surprenante d'orthologues chez des groupes encore plus distants, dont les Cnidaires, les Placozoaires, et meme de nombreux Procaryotes. Par ailleurs, la caracterisation d'une ECA active chez une Proteobacterie indique que l'enzyme ancestrale serait fonctionnelle. Ainsi, l'ECA est presente des Procaryotes aux Mammiferes. Ses proprietes moleculaires, biochimiques et structurales sont incroyablement conservees. L'absence d'ECA dans tous les genomes d'Eucaryotes bicontes sequences a ce jour pourrait alors resulter d'une perte secondaire. L'ensemble de ces elements suggere que l'ECA serait apparue tres tot au cours de la phylogenese. Les caracteristiques de l'ECA mammalienne refleteraient la longue evolution d'une enzyme ancestrale peu specialisee, dont les fonctions restent enigmatiques.
The formation of blood cells and vascular networks occurs simultaneously during development, and both lineages remain in close association in all adult tissues. The functional setting of both systems within the embryo and their renewal during adult life are highly complex processes, and require the involvement of numerous molecular actors, the activities of which are often overlapping. Here, I review the activity of TAL-1, a basic-helix-loop-helix transcription factor, which plays a key role in the formation and functioning of both blood and endothelial systems, with a particular emphasis on recent data that associate TAL-1 with angiogenesis.
Depuis plusieurs decennies, les anti-oxydants ont ete beaucoup etudies, et les scientifiques cherchent a prouver leurs effets preventifs et curatifs dans certaines pathologies chroniques. Cependant, il n’est pas rare de trouver des etudes cliniques aux resultats tres contradictoires, ce qui peut expliquer en partie la perte d’engouement du consommateur pour les complements alimentaires anti-oxydants. Avant toute chose, des definitions doivent etre revues, comme celle des radicaux libres (RL) ; ils ne sont pas tous toxiques. Certains d’entre eux, comme le monoxyde d’azote, sont necessaires au bon fonctionnement physiologique de l’organisme, et les eliminer serait une erreur ! Par contre, d’autres especes reactives de l’oxygene (ROS), qui ne sont pas des RL, sont toxiques pour l’organisme ; c’est le cas du peroxyde d’hydrogene qui est toxique. Nous avons egalement redefini le stress oxydatif : il n’est pas le simple resultat d’un desequilibre entre oxydants et anti-oxydants, mais egalement la consequence du desequilibre de l’etat redox cellulaire. Les mecanismes d’action, la biodisponibilite, la synergie et les methodes de dosage des anti-oxydants sont des themes tres sensibles, et il est primordial de les etudier en profondeur si l’on veut aboutir a des etudes cliniques fiables. Face a l’echec des etudes cliniques utilisant les anti-oxydants, nous avons tente d’expliquer les strategies a suivre. Tout d’abord, la nature de l’anti-oxydant est importante, il faut toujours preferer un anti-oxydant d’origine naturelle. Ensuite, nous avons explique que l’effet-dose etait certainement responsable de l’echec des essais. En effet, la dose administree dans les etudes etait soit trop faible pour obtenir des resultats significatifs, soit trop forte, devenant ainsi pro-oxydante et eliminant la concentration basale de ROS (role physiologique). Nous avons mis en lumiere de nouveaux mecanismes, comme l’implication de la mitochondrie et des phenomenes de glycation dans l’etablissement d’une multitude de physiopathologies. La nutrigenomique et la nutrigenetique ont ete abordees : elles etudient les interactions entre le patrimoine genetique et l’alimentation. Le polymorphisme genetique explique la variabilite de l’absorption des micronutriments. Ce dernier theme aboutit a affirmer la necessite de fournir le bon anti-oxydant, en quantite adequate, au bon endroit et au bon moment et pour un individu particulier. Pour accroitre la capacite anti-oxydante globale de l’organisme, il faut augmenter l’apport exogene en anti-oxydants ou stimuler la synthese endogene d’anti-oxydants (SOD, GPX, GSH). D’autre part, il faut cibler la mitochondrie et intensifier sa defense globale (veritable defi a relever), augmenter la biodisponibilite des anti-oxydants, et etudier leur passage a travers la barriere hemato-encephalique.
Cet exposé a pour but de montrer quels sont les précautions prises avant de mettre une plante génétiquement modifiée (PGM) sur le marché. La première partie présente les événements biologiques qui se produisent de manière permanente au cours de la vie de la cellule et d'un organisme. L'événement biologique que représente une transgénèse n'est pas quelque chose d'inconnu pour les cellules. La deuxième partie présente l'évaluation qui est faite des PGM avant de les mettre sur le marché et qui, en France, suit les lignes directrices de l'AESA (Autorité Européenne de Sécurité Alimentaire). La troisième évoque des questions fréquemment posées dans le débat sur les PGM. Il est conclu que les PGM sont au moins aussi sûres pour l'alimentation humaine et animale que leur contrepartie non-GM.
