Evénements traumatiques et réponses de stress: le rôle de l'ocytocine et de l'attachement [Traumatic events and stress responses: the role of oxytocin and attachement].

Being repeatedly confronted to very difficult situations since childhood influences the way indivuals will later respond to even mildly stressful events. The hypothalamic-pituitary-adrenal axis (HPA) is a complex system implicated in regulating neuroendocrine responses to stress. Its activation produces among others the <stress hormonea, cortisol. However, the regulation of the physiological response to stress depends on psychological factors linked with the representations that individuals develop regarding their close relationships i.e. attachment. Furthermore, attachment representations seem to be associated with oxytocin, a hormone involved both in cortisol reduction and in positive social behaviours.

Correlative light and electron microscopy in parasite research.

The interaction of a parasite and a host cell is a complex process, which involves several steps: (1) attachment to the plasma membrane, (2) entry inside the host cell, and (3) hijacking of the metabolism of the host. In biochemical experiments, only an event averaged over the whole cell population can be analyzed. The power of microscopy, however, is to investigate individual events in individual cells. Therefore, parasitologists frequently perform experiments with fluorescence microscopy using different dyes to label structures of the parasite or the host cell. Though the resolution of light microscopy has greatly improved, it is not sufficient to reveal interactions at the ultrastructural level. Furthermore, only specifically labeled structures can be seen and related to each other. Here, we want to demonstrate the additional value of electron microscopy in this area of research. Investigation of the different steps of parasite-host cell interaction by electron microscopy, however, is often hampered by the fact that there are only a few cells infected, and therefore it is difficult to find enough cells to study. A solution is to profit from low magnification, hence large overview, and specific location of the players by fluorescence labels in a light microscope with the high power resolution and structural information provided by an electron microscope, in short by correlative light and electron microscopy.

Biosphere/lithosphere interface : microbially-mediated CaCO3 precipitation in hypersaline and freshwater environments

Abstract: Microbial mats very efficiently cycle elements, such as C, 0, N, S and H, which makes them key players of redox processes at the biosphere-lithosphere interface. They are characterized by high metabolic activities and high turnover rates (production and consumption) of biomass, which mainly consists of cell material and of extracellular organic matter (EOM). The EOM forms a matrix, embedding the microbial cells and fulfilling various functions within the microbial mat, including: mat attachment to surfaces; creation of micro-domains within the mat; physical stabilization under hy- drodynamic stress and the protection of the cells in multiple other stress conditions. EOM mainly consists of polysaccharides, amino acids, and a variety of chemical func-tional groups {e.g., -C00H, - SH -OH). These groups strongly bind cations such as Ca2+ and Mg2+ and thus exert a strong control on carbonate mineral formation within the microbial mat. A feedback mechanism between community metabolisms, their prod¬ucts, and the surrounding physicochemical microenvironment thus influences the de¬gree of carbonate saturation favoring either carbonate precipitation or dissolution. We investigated the driving forces and mechanisms of microbialite formation in the Sari ne River, FR, Switzerland, the hypersaline lake, Big Pond, Bahamas and in labo¬ratory experiments. The two fundamentally different natural systems allowed us to compare the geochemical conditions and microbial metabolisms, necessary for car¬bonate formation in microbial mats. Although carbonates are oversaturated in both environments, precipitation does not occur on physicochemical substrates (i.e. out¬side the microbial mats). In the Sarine a high crystal nucleation threshold exceeds the carbonate saturation, despite the high carbonate alkalinity in the water column. Cyanobacterial photosynthesis strongly locally enhances the carbonate alkalinity, whereas the EOM attract and immobilize calcium, which increases the saturation state and finally leads to carbonate precipitation within the EOM (in this case the cyanobacterial sheath) as nucleation template. In Big Pond, the presence of calcium- chelating anions (i.e. sulfate) and EOM, as well as the presence of magnesium, lowers the calcium activity in the water column and mat, and thus inhibits carbonate pre¬cipitation. Coupled with other heterotrophic metabolisms, sulfate reduction uses the EOM as carbon source, degrading it. The resulting EOM consumption creates alkalin¬ity, releases calcium and consumes sulfate in mat-micro domains, which leads to the formation of carbonate layers at the top of the microbial mat. Résumé: Interface biosphère/lithosphère: médiation microbienne de la précipitation de CaC03 dans des environnements en eaux douces et hypersalines Les tapis microbiens engendrent une circulation très efficace des éléments, tels que C, 0, N, S et H, ce qui en fait des acteurs clé pour les processus d'oxydoréduction à l'inter¬face biosphère-lithosphère. Ils sont caractérisés par des taux élevés d'activité méta¬bolique, ainsi que par la production et la consommation de biomasse, principalement constituée de cellules microbiennes et de matière organique extracellulaire (MOE). Dans un tapis microbien, les cellules microbiennes sont enveloppées par une matrice de MOE qui a différentes fonctions dont l'attachement du tapis aux surfaces, la créa¬tion de micro-domaines dans le tapis, la stabilisation physique en situation de stress hydrodynamique, et la protection des cellules dans de multiples autres conditions de stress. La MOE se compose principalement de polysaccharides, d'acides aminés, et d'une variété de groupes fonctionnels chimiques (par exemple, COOH, -SH et -OH). Ces groupes se lient fortement aux cations, tels que Ca2+ et Mg2+, et exercent ainsi un contrôle fort sur la formation de CaC03 dans le tapis microbien. Un mécanisme de rétroaction, entre les métabolismes de la communauté microbienne, leurs produits, et le microenvironnement physico-chimique, influence le degré de saturation de car¬bonate, favorisant soit leur précipitation, soit leur dissolution. Nous avons étudié le moteur et les mécanismes de minéralisation dans des tapis de la Sarine, FR, Suisse et du lac hypersalin, Big Pond, aux Bahamas, ainsi que durant des expériences en laboratoire. Les deux systèmes naturels, fondamentalement dif¬férents, nous ont permis de comparer les conditions géochimiques et les métabolis¬mes nécessaires à la formation des carbonates dans des tapis microbiens. Bien que les carbonates soient sursaturés dans les deux environnements, la précipitation ne se produit pas sur des substrats physico-chimiques (en dehors du tapis microbien). Dans la Sarine, malgré un taux d'alcalinité élevé, les valeurs de seuil pour la nucléa- tion de carbonates sont plus hautes que la saturation du carbonate. La photosynthèse cyanobactérienne augmente localement l'alcalinité, alors que la MOE attire et immo¬bilise le calcium, ce qui augmente l'état de saturation et conduit finalement à la pré¬cipitation des carbonates, en utilisant la MOE comme substrat de nucléation. À Big Pond, la présence de chélateurs de calcium, notamment les anions (p.ex. le sulfate) et la MOE, ainsi que la présence de magnésium, réduit l'activité du calcium et inhibe en conséquence la précipitation des carbonates. Couplée avec d'autres métabolismes hétérotrophes, la réduction des sulfates utilise la MOE comme source de carbone, en la dégradant. Cette consommation de MOE crée l'alcalinité, consomme des sulfates et libère du calcium dans des micro-domaines, conduisant à la formation de couches de carbonates dans le haut du tapis microbien.

The complete amino acid sequence for brain beta spectrin (beta fodrin): relationship to globin sequences.

The amino acid sequence of mouse brain beta spectrin (beta fodrin), deduced from the nucleotide sequence of complementary DNA clones, reveals that this non-erythroid beta spectrin comprises 2363 residues, with a molecular weight of 274,449 Da. Brain beta spectrin contains three structural domains and we suggest the position of several functional domains including f-actin, synapsin I, ankyrin and spectrin self association sites. Analysis of deduced amino acid sequences indicated striking homology and similar structural characteristics of brain beta spectrin repeats beta 11 and beta 12 to globins. In vitro analysis has demonstrated that heme is capable of specific attachment to brain spectrin, suggesting possible new functions in electron transfer, oxygen binding, nitric oxide binding or heme scavenging.

A collagen-poly(lactic acid-co-ɛ-caprolactone) hybrid scaffold for bladder tissue regeneration.

Scaffold materials should favor cell attachment and proliferation, and provide designable 3D structures with appropriate mechanical strength. Collagen matrices have proven to be beneficial scaffolds for tissue regeneration. However, apart from small intestinal submucosa, they offer a limited mechanical strength even if crosslinking can enhance their mechanical properties. A more cell-friendly way to increase material strength is to combine synthetic polymer meshes with plastic compressed collagen gels. This work describes the potential of plastic compressed collagen-poly(lactic acid-co-ɛ-caprolactone) (PLAC) hybrids as scaffolds for bladder tissue regeneration. Human bladder smooth muscle and urothelial cells were cultured on and inside collagen-PLAC hybrids in vitro. Scaffolds were analyzed by electron microscopy, histology, immunohistochemistry, and AlamarBlue assay. Both cell types proliferated in and on the hybrid, forming dense cell layers on top after two weeks. Furthermore, hybrids were implanted subcutaneously in the backs of nude mice. Host cell infiltration, scaffold degradation, and the presence of the seeded bladder cells were analyzed. Hybrids showed a lower inflammatory reaction in vivo than PLAC meshes alone, and first signs of polymer degradation were visible at six months. Collagen-PLAC hybrids have potential for bladder tissue regeneration, as they show efficient cell seeding, proliferation, and good mechanical properties.

Le développement des interactions triadiques mère-père-enfant = The development of mother-father-child triadic interactions

Cet article présente un état des lieux des recherches menées selon le paradigme de « l'alliance familiale » sur le développement des interactions triadiques mère-père-enfant lors de la transition à la parentalité. Ces recherches ont montré tout d'abord que la qualité des interactions triadiques tend à être stable au cours des deux premières années de vie de l'enfant, et qu'elle peut être anticipée durant la grossesse par l'observation d'interactions dans une simulation de jeu triadique. Ensuite, elles ont montré qu'une altération de ces interactions a une influence sur le développement de l'enfant qui se manifeste tout au long des cinq premières années, tant au niveau affectif que cognitif (par exemple : la capacité d'attention triangulaire lors des premiers mois, ou le développement de la théorie de l'esprit et les difficultés de comportements à cinq ans). Cette influence s'exerce en plus de celle d'autres variables comme la relation d'attachement mère-enfant, ou la personnalité de l'enfant lui-même évaluée selon son tempérament. La triade constitue donc un contexte de développement en soi qui doit être pris en compte dans la prise en charge et l'intervention auprès de jeunes enfants.This paper presents the main results of researches on the development of mother-father-child triadic interactions during the transition to parenthood, according to the « family alliance » model. First, these researches have shown that the quality of triadic interactions tends to be stable through the first two years, and that it can be predicted during pregnancy by observation of a simulated triadic play. Then, they have shown that disturbances in triadic interactions have an impact on several affective and cognitive developmental outcomes for the child throughout the first five years (for example, the triangular attention capacity during the first months, or the development of theory of mind and externalized behaviors at age five). This impact is specific, and triadic interactions exert an influence on the development of the child over and above other variables like the mother-child attachment relationship, or the personality of the child assessed in terms of temperament. The triad constitutes then a context of development per se which has to be taken into account when working clinically with young children.

Optic nerve haemangioblastoma mimicking a planum sphenoidale meningioma.

Haemangioblastomas are rarely seen in the suprasellar region, arising from the optic apparatus or pituitary stalk, mimicking meningiomas on the preoperative MRI scan. They may be suspected in the presence of large flow voids and the absence of a dural tail. Intraoperatively, the extreme vascularity and compressibility of the tumour with no dural attachment should alert the surgeon to the diagnosis. A complete resection with preservation of vision may be successfully attempted because of the well-demarcated tumour-nerve interface.

The significant behavioral aspects of adopted children within successful adoption in Romania

The human behavior is giving the entire picture of a person. The behavior is based on a complex combination of personal innate factors, experience and education and the social network within which the individual is integrated. Each moment the complex individual factors face external and internal environmental aspects which in turn, generate proactive and retroactive reactions. The adoption process is an important and challenging social experiment, bringing to the adopted child a new affiliation, social network, experiences and educational standards. This comes in his/her life after the trauma of losing his biological affiliation and social and emotional support. Which are the significant characteristics of the adopted child's behavior? Which are the behavioral characteristics of the adoptive child that guarantee the success of the domestic adoptions in Romania? These are the questions we are going to answer here based on the research done within FISAN(6) project. The 32 children, 11-16 years old, adopted by Romanian families, during the early ages (0-4 years), were evaluated with complex evaluation tools for children and parents. The adoptive families participating in the research live in the Western counties of Romania.Successful adoption is defined as secure attachment of the adopted child. The conclusions emphasize the importance of: the pro-social behavior, the loving behavior showed to the parents, the assertive behavior, the differentiations between parents and people outside the family, and between the two parents, and the humor. These behaviors displayed by the adopted children are the ingredients of a successful integration within the adoptive family.

Comparison of radial deformability of stent posts of different aortic bioprostheses.

OBJECTIVES Little is known about the stent deformability required for optimal stented heart valve bioprosthesis design. Therefore, two bioprosthetic valves with known good long-term clinical results were tested. The strain in the radial direction of the stent posts of these valves was compared with contemporary bioprosthetic valves and a native porcine aortic root. METHODS Medtronic Intact and Carpentier-Edwards Standard (CES), and four contemporary bioprostheses, including one self-expanding prosthesis, were tested with three sonomicrometry probes per valve fixed at commissure attachment points. The mean values from 2400 data points from three measurements of the interprobe distances were used to calculate the radius of the circle circumscribed around the three probes. Changes in the radius of the aortic root at pressures 70-90 and 120-140 mmHg (pressure during diastole and systole) and that of the stent posts at 70-90 and 0-10 mmHg (transvalvular pressure gradient during diastole and systole) were compared. RESULTS An increase in radius by 7.3 ± 2.6, 8.7 ± 0.0 and 3.9 ± 0.0% for the porcine aortic root, CES and Intact valves, respectively, was observed during transition from diastolic to systolic pressure and less for contemporary bioprostheses-mean 2.5 ± 0.9%, lowest 1.2 ± 0.0. CONCLUSIONS The results indicate that the radial deformability of bioprosthetic valve stent posts can be as low as 1.2% for xenoaortic and 3.0% for xenopericardial prostheses with no compromise of valve durability. Although these results suggest that valve stent post-deformability might not be of critical importance, a concrete answer to the question of the significance of stent deformability for valve durability can be obtained only by acquiring long-term follow-up results for valve prostheses with rigid stents.

Emotion, Affect, Sentiment: The Language and Aesthetics of Feeling

Bringing together experts from linguistics, medieval and modern literary studies, this volume offers a transhistorical look at the language and cultural work of emotion in a variety of written, oral and visual texts. Contributors engage with the recent so-called affective turn, but also examine the language and use of emotion from a variety of perspectives, touching on issues such as Romantic and Modernist aesthetics, the history of emotions, melodramatic and the Gothic, reception aesthetics, rudeness, and medicine.

Discovery of novel arenavirus receptors and entry factors

Arenaviruses are enveloped negative-strand RNA viruses that contain a bi-segmented genome. They are rodent-borne pathogens endemic to the Americas and Africa, with the exception of lymphocytic choriomeningitis virus (LCMV) that is world-wide distributed. The arenaviruses include numerous important human pathogens including the Old World arenavirus Lassa virus (LASV), the causative agent of a severe viral hemorrhagic fever in humans with several hundred thousand infections per year in Africa and thousands of deaths. Viruses are obligatory intracellular parasites, strictly depending on cellular processes and factors to complete their replication cycle. The binding of a virus to target cells is the first step of every viral infection, and is mainly mediated by viral proteins that can directly engage cellular receptors, providing a key determinant for viral tropism. This early step of infection represents a promising target to block the pathogen before it can take control over the host cell. Old World arenaviruses, such as LASV and LCMV, bind to host cells via attachment to their main receptor, dystroglycan (DG), an ubiquitous receptor for extracellular matrix proteins. The engagement of DG by LASV results in a fast internalization and transfer the virus to late endosomal compartment suggesting that the virus binding to DG causes marked changes in the dynamics of the receptor. These events could result in the clustering of the receptor and subsequent induction of signaling that could be modulated by the virus. Recently, numerous findings also suggest the presence of alternative receptor(s) for LASV in absence of the main DG receptor. In my first project, I was interested to investigate the effects of virus-receptor binding on the tyrosine phosphorylation of the cytoplasmic domain of DG and to test if this post-translational modification was crucial for the internalization of the LASV-receptor complex. We found that engagement of cellular DG by a recombinant LCMV expressing the envelope GP of LASV in human epithelial cells induced tyrosine phosphorylation of the cytoplasmic domain of DG. LASV GP binding to DG further resulted in dissociation of the adapter protein utrophin from virus-bound DG. Virus-induced dissociation of utrophin and consequent virus internalization were affected by the broadly specific tyrosine kinase inhibitor genistein. We speculate that the detachment of virus- bound DG from the actin-based cytoskeleton following DG phosphorylation may facilitate subsequent endocytosis of the virus-receptor complex. In the second project, I was interested to characterize the newly indentified LASV alternative receptor Axl in the context of productive arenavirus infection. In a first step, we demonstrated that Axl supports productive infection by rLCMV-LASVGP in a DG-independent manner. In line with previous studies, cell entry of rLCMV-LASVGP via Axl was less efficient when compared to functional DG. Interestingly, Axl-mediated infection showed rapid kinetics similar to DG-dependent entry. Using a panel of inhibitors, we found that Axl-mediated cell entry of rLCMV-LASVGP involved a clathrin-independent pathway that critically depended on actin and dynamin and was sensitive to EIPA but not to PAK inhibitors, compatible with a macropinocytosis-like mechanism of entry. In a next step, we aimed to investigate the molecular mechanism by which rLCMV-LASVGP recognizes Axl. Phosphatidylserine (PS) is the natural ligand of Axl via the adaptor protein Gas6. We detected the presence of PS in the envelope of Old World arenaviruses, suggesting that PS could mediate Axl-virus binding, in a mechanism of apoptotic mimicry already described for other viruses. Whether envelope PS and/or the GP of LASV plays any role in virus entry via Axl is still an open question. The molecular mechanisms underlying host cell-virus interaction are of particular interest to answer basic scientific questions as well as to apply key findings to translational research. Understanding pathogen induced-signaling and its link to invasion of the host cell is of great importance to develop drugs for therapeutic intervention against highly pathogenic viruses like LASV. - Les Arenavirus sont des virus enveloppés à ARN négatifs organisés sous forme de génome bisegmenté. Ils sont véhiculés par les rongeurs et se retrouvent de manière endémique aux Amériques et en Afrique avec l'exception du virus de la chorioméningite lymphocytaire (LCMV) qui lui est distribué mondialement. De nombreux pathogènes humains font parti de la famille des Arenavirus dont le virus de l'Ancien Monde Lassa (LASV), un agent responsable de fièvres hémorragiques sévères chez les humains. Le virus de Lassa cause plusieurs centaines de milliers d'infections par année en Afrique ainsi que des milliers de morts. De manière générale, les virus sont des parasites intracellulaires obligatoires qui dépendent strictement de processus et facteurs cellulaires pour clore leur cycle de réplication. L'attachement d'un virus à sa cellule cible représente la première étape de chaque infection virale et est principalement dirigée par des protéines virales qui interagissent directement avec leur récepteurs cellulaires respectifs fournissant ainsi un indicateur déterminant pour le tropisme d'un virus. Cette première étape de l'infection représente aussi une cible prometteuse pour bloquer le pathogène avant qu'il ne puisse prendre le contrôle de la cellule. Les Arenavirus de l'Ancien Monde comme LASV et LCMV s'attachent à la cellule hôte en se liant à leur récepteur principal, le dystroglycan (DG), un récepteur ubiquitaire pour les protéines de la matrice extracellulaire. La liaison du DG par LASV résulte en une rapide internalisation transférant le virus aux endosomes tardifs suggérant ainsi que l'attachement du virus au DG peut provoquer des changements marqués dans la dynamique moléculaire du récepteur. Ces événements sont susceptibles d'induire un regroupement du récepteur à la surface cellulaire, ainsi qu'une induction subséquente qui pourrait être, par la suite, modulée par le virus. Récemment, plusieurs découvertes suggèrent aussi la présence d'un récepteur alternatif pour LASV en l'absence du récepteur principal, le DG. Concernant mon premier projet, j'étais intéressée à étudier les effets de la liaison virus- récepteur sur la phosphorylation des acides aminés tyrosines se trouvant dans la partie cytoplasmique du DG, le but étant de tester si cette modification post-translationnelle était cruciale pour Γ internalisation du complexe LASV-DG récepteur. Nous avons découvert que l'engagement du récepteur DG par le virus recombinant LCMV, exprimant la glycoprotéine de LASV, dans des cellules épithéliales humaines induit une phosphorylation de résidu(s) tyrosine se situant dans le domaine cytoplasmique du DG. La liaison de la glycoprotéine de LASV au DG induit par la suite la dissociation de la protéine adaptatrice utrophine du complexe virus-DG récepteur. Nous avons observé que cette dissociation de l'utrophine, induite par le virus, ainsi que son internalisation, sont affectées par l'inhibiteur à large spectre des tyrosines kinases, la génistéine. Nous avons donc supposé que le détachement du virus, lié au récepteur DG, du cytosquelette d'actine suite à la phosphorylation du DG faciliterait l'endocytose subséquente du complexe virus-récepteur. Dans le second projet, j'étais intéressée à caractériser le récepteur alternatif Axl qui a été récemment identifié dans le contexte de l'infection productive des Arenavirus. Dans un premier temps, nous avons démontré que le récepteur alternatif Axl permet l'infection des cellules par le virus LCMV recombinant LASV indépendamment du récepteur DG. Conformément aux études publiées précédemment, nous avons pu observer que l'entrée du virus recombinant LASV via Axl est moins efficace que via le récepteur principal DG. De façon intéressante, nous avons aussi remarqué que l'infection autorisée par Axl manifeste une cinétique virale d'entrée similaire à celle observée avec le récepteur DG. Utilisant un éventail de différents inhibiteurs, nous avons trouvé que l'entrée du virus recombinant rLCMV-LASVGP via Axl implique une voie d'entrée indépendante de la clathrine et dépendant de manière critique de l'actine et de la dynamine. Cette nouvelle voie d'entrée est aussi sensible à l'EIPA contrairement aux inhibiteurs PAK indiquant un mécanisme d'entrée compatible avec un mécanisme de macropinocytose. L'étape suivante du projet a été d'investiguer le mécanisme moléculaire par lequel le virus recombinant rLCMV-LASVGP reconnaît le récepteur alternatif Axl. La phosphatidylsérine (PS) se trouve être un ligand naturel pour Axl via la protéine adaptatrice Gas6. Nous avons détecté la présence de PS dans l'enveloppe des Arenavirus du Vieux Monde suggérant que la PS pourrait médier la liaison du virus à Axl dans un mécanisme de mimétisme apoptotique déjà observé et décrit pour d'autres virus. Cependant, il reste encore à déterminer qui de la PS ou de la glycoprotéine de l'enveloppe virale intervient dans le processus d'entrée de LASV via le récepteur alternatif Axl. Les mécanismes moléculaires à la base de l'interaction entre virus et cellule hôte sont d'intérêts particuliers pour répondre aux questions scientifiques de base ainsi que dans l'application de découvertes clés pour la recherche translationnelle. La compréhension de la signalisation induite par les pathogènes ainsi que son lien à l'invasion de la cellule hôte est d'une importance considérable pour le développement de drogues pour l'intervention thérapeutique contre les virus hautement pathogènes comme LASV.

MAR elements regulate the probability of epigenetic switching between active and inactive gene expression.

Gene expression often cycles between active and inactive states in eukaryotes, yielding variable or noisy gene expression in the short-term, while slow epigenetic changes may lead to silencing or variegated expression. Understanding how cells control these effects will be of paramount importance to construct biological systems with predictable behaviours. Here we find that a human matrix attachment region (MAR) genetic element controls the stability and heritability of gene expression in cell populations. Mathematical modeling indicated that the MAR controls the probability of long-term transitions between active and inactive expression, thus reducing silencing effects and increasing the reactivation of silent genes. Single-cell short-terms assays revealed persistent expression and reduced expression noise in MAR-driven genes, while stochastic burst of expression occurred without this genetic element. The MAR thus confers a more deterministic behavior to an otherwise stochastic process, providing a means towards more reliable expression of engineered genetic systems.

Use of human MAR elements to improve retroviral vector production.

Retroviral vectors have many favorable properties for gene therapies, but their use remains limited by safety concerns and/or by relatively lower titers for some of the safer self-inactivating (SIN) derivatives. In this study, we evaluated whether increased production of SIN retroviral vectors can be achieved from the use of matrix attachment region (MAR) epigenetic regulators. Two MAR elements of human origin were found to increase and to stabilize the expression of the green fluorescent protein transgene in stably transfected HEK-293 packaging cells. Introduction of one of these MAR elements in retroviral vector-producing plasmids yielded higher expression of the viral vector RNA. Consistently, viral titers obtained from transient transfection of MAR-containing plasmids were increased up to sixfold as compared with the parental construct, when evaluated in different packaging cell systems and transfection conditions. Thus, use of MAR elements opens new perspectives for the efficient generation of gene therapy vectors.

Trauma et mémoire - quand la douleur infiltre le corps et l'âme: un regard sur les toxicodépendances graves

This article describes the long-lasting psychological after-effects of a traumatic experience. There is growing lmowledge of the biomedical underpinnings of these phenomena: the underlying mechanisms belong to an implicit learning process whereby the victim remains under the influence of painful past experiences. One of these mechanisms concerns the development of a traumatic bonding which Iioticeably impedes the establishment of interpersona! relationships. The other mechanism, called "contextualisation deficit", is the difficulty of adjusting a person's emotional and behavioural reactivity to the context of present day !ife. This capacity of a traumatic experience to become incrusted long-termina human being's mind, and to haunt the victim with various forms of psychological and physical suffering, can be compared with the presence of a tumour or an abscess in somatic medicine. Th us, severe drug addiction can be conceptualised as a disorder in which the patient tries - in most cases ineffectively - to soothe the pain of today's world in cmmection with the trauma of the past. In conclusion, this article urges the development of psychiatrie care programmes which operate at the centre of the suffering encountered by the se patients, as a complement to the already well-established offers such as harm reduction, substitution therapy and social support.