Experimental calcium oxalate crystal production and dissolution by selected wood rot fungi.

Twenty-six species of white-rotting Agaricomycotina fungi (Basidiomycota) were screened for their ability to produce calcium-oxalate (CaOx) crystals in vitro. Most were able to produce CaOx crystals in malt agar medium in the absence of additional calcium. In the same medium enriched with Ca2+, all the species produced CaOx crystals (weddellite or whewellite). Hyphae of four species (Ganoderma lucidum, Polyporus ciliatus, Pycnoporus cinnabarinus, and Trametes versicolor) were found coated with crystals (weddellite/whewellite). The production of CaOx crystals during the growth phase was confirmed by an investigation of the production kinetics for six of the species considered in the initial screening (Pleurotus citrinopileatus, Pleurotus eryngii, Pleurotus ostreatus, P. cinnabarinus, Trametes suaveolens, and T. versicolor). However, the crystals produced during the growth phase disappeared from the medium over time in four of the six species (P. citrinopileatus, P. eryngii, P. cinnabarinus, and T. suaveolens). For P. cinnabarinus, the disappearance of the crystals was correlated with a decrease in the total oxalate concentration measured in the medium from 0.65 μg mm−2 (at the maximum accumulation rate) to 0.30 μg mm−2. The decrease in the CaOx concentration was correlated with a change in mycelia morphology. The oxalate dissolution capability of all the species was also tested in a medium containing calcium oxalate as the sole source of carbon (modified Schlegel medium). Three species (Agaricus blazei, Pleurotus tuberregium, and P. ciliatus) presented a dissolution halo around the growth zone. This study shows that CaOx crystal production is a widespread phenomenon in white-rot fungi, and that an excess of Ca2+ can enhance CaOx crystal production. In addition, it shows that some white-rot fungal species are capable of dissolving CaOx crystals after growth has ceased. These results highlight a diversity of responses around the production or dissolution of calcium oxalate in white-rot fungi and reveal an unexpected potential importance of fungi on the oxalate cycle in the environment.

Stress Perception in Public Organizations: Expanding the Job Demands - Job Resources Model by Including Public Service Motivation

Although stress has been a longstanding issue in organizations and management studies, it has never been studied in relation to Public Service Motivation. This article therefore aims to integrate PSM into the job demands-job resources model of stress in order to determine whether PSM might contribute to stress in public organizations. Drawing upon original data from a questionnaire in a Swiss municipality, this study unsurprisingly shows that "red tape" is an antecedent of stress perception, whereas satisfaction with organizational support, positive feedback, and recognition significantly decrease the level of perceived stress. Astonishingly, the empirical results show that PSM is positively and significantly related to stress perception. By increasing individuals' expectations towards their jobs, PSM might thus contribute to increased pressure on public agents. Ultimately, this article investigates the "dark side" of PSM, which has been neglected by the literature thus far.

Antecedents of Job Satisfaction, Organizational Commitment and Stress in a Public Hospital: A P-E Fit Perspective

This article tests different P-E fit dimensions in order to assess their impact on three work outcomes: job satisfaction; organizational commitment; and stress perception. Findings shows that P-E fit dimensions have differentiated effects on its dependent variables. This study contributes to several important academic discussions. The first concerns the model tested, which contains several P-E fit dimensions. The second scientific contribution is to consider P-E fit dimensions as antecedents of three job outcomes. The third contribution concerns the development and testing of a new P-E fit dimension called "person-reforms" fit.

Bentho-planktonic evidence from the Austrian Alps for a decline in sea-surface carbonate production at the end of the Triassic

A high-resolution micropalaeontological study, combined with geochemical and sedimentological analyses was performed on the Tiefengraben, Schlossgraben and Eiberg sections (Austrian Alps) in order to characterize sea-surface carbonate production during the end-Triassic crisis. At the end-Rhaetian, the dominant calcareous nannofossil Prinsiosphaera triassica shows a decrease in abundance and size and this is correlated with a increase in delta O-18 and a gradual decline in delta C-13(carb) values. Simultaneously, benthic foraminiferal assemblages show a decrease in diversity and abundance of calcareous taxa and a dominance of infaunal agglutinated taxa. The smaller size of calcareous nannofossils disturbed the vertical export balance of the biological carbon pump towards the sea-bottom, resulting in changes in feeding strategies within the benthic foraminiferal assemblages from deposit feeders to detritus feeders and bacterial scavengers. These micropalaeontological data combined with geochemical proxies suggest that changes in seawater chemistry and/or cooling episodes might have occurred in the latest Triassic, leading to a marked decrease of carbonate production. This in turn culminated in the quasi-absence of calcareous nannofossils and benthic foraminifers in the latest Triassic. The aftermath (latest Triassic earliest Jurassic) was characterised by abundance peaks of ``disaster'' epifaunal agglutinated foraminifera Trochammina on the sea-floor. Central Atlantic Magmatic Province (CAMP) paroxysmal activity, superimposed on a major worldwide regressive phase, is assumed to be responsible for a deterioration in marine palaeoenvironments. CAMP sulfuric emissions might have been the trigger for cooling episodes and seawater acidification leading to disturbance of the surface carbonate production at the very end-Triassic.

Organisational PSM Antecedents. Do HRM Practices Matter? Testing the Mediating Role of Job Satisfaction and Organisational Commitment

The present study aims to identify organisational antecedents of public service motivation (PSM). Numerous research has been devoted to the identification of socio-demographic PSM antecedents, or to its outcomes. However, organisational antecedents are understudied thus far. In order to fill this research gap, we question whether human resources management practices, whether intrinsic or extrinsic ones, might be related to PSM. Drawing on person-environment fit theoretical assumptions, we depart from the idea that PSM may be developed or sustained by HRM practices, which might contribute to create an environment allowing public employees to fulfill their needs or personal aspirations. Based upon a survey in an important Swiss municipality (N = 859), our findings surprisingly highlight that extrinsic HRM practices are significantly related to PSM, whereas intrinsic ones are not. Furthermore, when taking into account work-related outcomes, such as job satisfaction and organisational commitment, there is evidence of full mediation effects towards extrinsic HRM practices from organisational commitment. Astonishingly, neither job satisfaction nor intrinsic HRM practices are significantly related to PSM.

Financial Markets and Real Ecinomy: Four Essays in International Trade

Financial markets play an important role in an economy performing various functions like mobilizing and pooling savings, producing information about investment opportunities, screening and monitoring investments, implementation of corporate governance, diversification and management of risk. These functions influence saving rates, investment decisions, technological innovation and, therefore, have important implications for welfare. In my PhD dissertation I examine the interplay of financial and product markets by looking at different channels through which financial markets may influence an economy.My dissertation consists of four chapters. The first chapter is a co-authored work with Martin Strieborny, a PhD student from the University of Lausanne. The second chapter is a co-authored work with Melise Jaud, a PhD student from the Paris School of Economics. The third chapter is co-authored with both Melise Jaud and Martin Strieborny. The last chapter of my PhD dissertation is a single author paper.Chapter 1 of my PhD thesis analyzes the effect of financial development on growth of contract intensive industries. These industries intensively use intermediate inputs that neither can be sold on organized exchange, nor are reference-priced (Levchenko, 2007; Nunn, 2007). A typical example of a contract intensive industry would be an industry where an upstream supplier has to make investments in order to customize a product for needs of a downstream buyer. After the investment is made and the product is adjusted, the buyer may refuse to meet a commitment and trigger ex post renegotiation. Since the product is customized to the buyer's needs, the supplier cannot sell the product to a different buyer at the original price. This is referred in the literature as the holdup problem. As a consequence, the individually rational suppliers will underinvest into relationship-specific assets, hurting the downstream firms with negative consequences for aggregate growth. The standard way to mitigate the hold up problem is to write a binding contract and to rely on the legal enforcement by the state. However, even the most effective contract enforcement might fail to protect the supplier in tough times when the buyer lacks a reliable source of external financing. This suggests the potential role of financial intermediaries, banks in particular, in mitigating the incomplete contract problem. First, financial products like letters of credit and letters of guarantee can substantially decrease a risk and transaction costs of parties. Second, a bank loan can serve as a signal about a buyer's true financial situation, an upstream firm will be more willing undertake relationship-specific investment knowing that the business partner is creditworthy and will abstain from myopic behavior (Fama, 1985; von Thadden, 1995). Therefore, a well-developed financial (especially banking) system should disproportionately benefit contract intensive industries.The empirical test confirms this hypothesis. Indeed, contract intensive industries seem to grow faster in countries with a well developed financial system. Furthermore, this effect comes from a more developed banking sector rather than from a deeper stock market. These results are reaffirmed examining the effect of US bank deregulation on the growth of contract intensive industries in different states. Beyond an overall pro-growth effect, the bank deregulation seems to disproportionately benefit the industries requiring relationship-specific investments from their suppliers.Chapter 2 of my PhD focuses on the role of the financial sector in promoting exports of developing countries. In particular, it investigates how credit constraints affect the ability of firms operating in agri-food sectors of developing countries to keep exporting to foreign markets.Trade in high-value agri-food products from developing countries has expanded enormously over the last two decades offering opportunities for development. However, trade in agri-food is governed by a growing array of standards. Sanitary and Phytosanitary standards (SPS) and technical regulations impose additional sunk, fixed and operating costs along the firms' export life. Such costs may be detrimental to firms' survival, "pricing out" producers that cannot comply. The existence of these costs suggests a potential role of credit constraints in shaping the duration of trade relationships on foreign markets. A well-developed financial system provides the funds to exporters necessary to adjust production processes in order to meet quality and quantity requirements in foreign markets and to maintain long-standing trade relationships. The products with higher needs for financing should benefit the most from a well functioning financial system. This differential effect calls for a difference-in-difference approach initially proposed by Rajan and Zingales (1998). As a proxy for demand for financing of agri-food products, the sanitary risk index developed by Jaud et al. (2009) is used. The empirical literature on standards and norms show high costs of compliance, both variable and fixed, for high-value food products (Garcia-Martinez and Poole, 2004; Maskus et al., 2005). The sanitary risk index reflects the propensity of products to fail health and safety controls on the European Union (EU) market. Given the high costs of compliance, the sanitary risk index captures the demand for external financing to comply with such regulations.The prediction is empirically tested examining the export survival of different agri-food products from firms operating in Ghana, Mali, Malawi, Senegal and Tanzania. The results suggest that agri-food products that require more financing to keep up with food safety regulation of the destination market, indeed sustain longer in foreign market, when they are exported from countries with better developed financial markets.Chapter 3 analyzes the link between financial markets and efficiency of resource allocation in an economy. Producing and exporting products inconsistent with a country's factor endowments constitutes a serious misallocation of funds, which undermines competitiveness of the economy and inhibits its long term growth. In this chapter, inefficient exporting patterns are analyzed through the lens of the agency theories from the corporate finance literature. Managers may pursue projects with negative net present values because their perquisites or even their job might depend on them. Exporting activities are particularly prone to this problem. Business related to foreign markets involves both high levels of additional spending and strong incentives for managers to overinvest. Rational managers might have incentives to push for exports that use country's scarce factors which is suboptimal from a social point of view. Export subsidies might further skew the incentives towards inefficient exporting. Management can divert the export subsidies into investments promoting inefficient exporting.Corporate finance literature stresses the disciplining role of outside debt in counteracting the internal pressures to divert such "free cash flow" into unprofitable investments. Managers can lose both their reputation and the control of "their" firm if the unpaid external debt triggers a bankruptcy procedure. The threat of possible failure to satisfy debt service payments pushes the managers toward an efficient use of available resources (Jensen, 1986; Stulz, 1990; Hart and Moore, 1995). The main sources of debt financing in the most countries are banks. The disciplining role of banks might be especially important in the countries suffering from insufficient judicial quality. Banks, in pursuing their rights, rely on comparatively simple legal interventions that can be implemented even by mediocre courts. In addition to their disciplining role, banks can promote efficient exporting patterns in a more direct way by relaxing credit constraints of producers, through screening, identifying and investing in the most profitable investment projects. Therefore, a well-developed domestic financial system, and particular banking system, would help to push a country's exports towards products congruent with its comparative advantage.This prediction is tested looking at the survival of different product categories exported to US market. Products are identified according to the Euclidian distance between their revealed factor intensity and the country's factor endowments. The results suggest that products suffering from a comparative disadvantage (labour-intensive products from capital-abundant countries) survive less on the competitive US market. This pattern is stronger if the exporting country has a well-developed banking system. Thus, a strong banking sector promotes exports consistent with a country comparative advantage.Chapter 4 of my PhD thesis further examines the role of financial markets in fostering efficient resource allocation in an economy. In particular, the allocative efficiency hypothesis is investigated in the context of equity market liberalization.Many empirical studies document a positive and significant effect of financial liberalization on growth (Levchenko et al. 2009; Quinn and Toyoda 2009; Bekaert et al., 2005). However, the decrease in the cost of capital and the associated growth in investment appears rather modest in comparison to the large GDP growth effect (Bekaert and Harvey, 2005; Henry, 2000, 2003). Therefore, financial liberalization may have a positive impact on growth through its effect on the allocation of funds across firms and sectors.Free access to international capital markets allows the largest and most profitable domestic firms to borrow funds in foreign markets (Rajan and Zingales, 2003). As domestic banks loose some of their best clients, they reoptimize their lending practices seeking new clients among small and younger industrial firms. These firms are likely to be more risky than large and established companies. Screening of customers becomes prevalent as the return to screening rises. Banks, ceteris paribus, tend to focus on firms operating in comparative-advantage sectors because they are better risks. Firms in comparative-disadvantage sectors finding it harder to finance their entry into or survival in export markets either exit or refrain from entering export markets. On aggregate, one should therefore expect to see less entry, more exit, and shorter survival on export markets in those sectors after financial liberalization.The paper investigates the effect of financial liberalization on a country's export pattern by comparing the dynamics of entry and exit of different products in a country export portfolio before and after financial liberalization.The results suggest that products that lie far from the country's comparative advantage set tend to disappear relatively faster from the country's export portfolio following the liberalization of financial markets. In other words, financial liberalization tends to rebalance the composition of a country's export portfolio towards the products that intensively use the economy's abundant factors.

Conserving biodiversity in production landscapes.

Alternative land uses make different contributions to the conservation of biodiversity and have different implementation and management costs. Conservation planning analyses to date have generally assumed that land is either protected or unprotected, and that the unprotected portion does not contribute to conservation goals. We develop and apply a new planning approach that explicitly accounts for the contribution of a diverse range of land uses to achieving conservation goals. Using East Kalimantan (Indonesian Borneo) as a case study, we prioritize investments in alternative conservation strategies and account for the relative contribution of land uses ranging from production forest to well-managed protected areas. We employ data on the distribution of mammals and assign species-specific conservation targets to achieve equitable protection by accounting for life history characteristics and home range sizes. The relative sensitivity of each species to forest degradation determines the contribution of each land use to achieving targets. We compare the cost effectiveness of our approach to a plan that considers only the contribution of protected areas to biodiversity conservation, and to a plan that assumes that the cost of conservation is represented by only the opportunity costs of conservation to the timber industry. Our preliminary results will require further development and substantial stakeholder engagement prior to implementation; nonetheless we reveal that, by accounting for the contribution of unprotected land, we can obtain more refined estimates of the costs of conservation. Using traditional planning approaches would overestimate the cost of achieving the conservation targets by an order of magnitude. Our approach reveals not only where to invest, but which strategies to invest in, in order to effectively and efficiently conserve biodiversity.

Reduced development of CD4-8-B220+ T cells but normal autoantibody production in lpr/lpr mice lacking major histocompatibility complex class I molecules.

The lpr gene has recently been shown to encode a functional mutation in the Fas receptor, a molecule involved in transducing apoptotic signals. Mice homozygous for the lpr gene develop an autoimmune syndrome accompanied by massive accumulation of double-negative (DN) CD4-8-B220+ T cell receptor-alpha/beta+ cells. In order to investigate the origin of these DN T cells, we derived lpr/lpr mice lacking major histocompatibility complex (MHC) class I molecules by intercrossing them with beta 2-microglobulin (beta 2m)-deficient mice. Interestingly, these lpr beta 2m-/- mice develop 13-fold fewer DNT cells in lymph nodes as compared to lpr/lpr wild-type (lprWT) mice. Analysis of anti-DNA antibodies and rheumatoid factor in serum demonstrates that lpr beta 2m-/- mice produce comparable levels of autoantibodies to lprWT mice. Collectively our data indicate that MHC class I molecules control the development of DN T cells but not autoantibody production in lpr/lpr mice and support the hypothesis that the majority of DN T cells may be derived from cells of the CD8 lineage.

A genetic and biochemical investigation of malondialdehyde production and turnover in Arabidopsis

Malondialdehyde (MDA) is a small reactive molecule which occurs ubiqui¬tous among eukaryotes. Interest in this molecule stems from the fact that it can be highly reactive. In green tissues of plants it is apparently formed pre¬dominantly by reactive oxygen species (ROS)-mediated non-enzymatic oxi¬dation (nLPO) of triunsaturated fatty acids (TFAs). MDA which is formed by nLPO is widely used as a disease marker and is regarded to be a cel-lular toxin. Surprisingly, sites of ROS production like mitochondria and chloroplasts possess membranes which are enriched in nLPO-prone polyun¬saturated fatty acids (PUFAs). In this work we showed that chloroplasts are the major site of MDA production in leaves of adult Arabidopsis thaliana plants, whereas analyses in seedlings revealed accumulation in meristematic tissues like the root tip, lateral roots and the apical meristem region. Char-acterizing the MDA pools in more detail, we could show that MDA in plants was predominantly present in a free, non-reactive enolate form. This might explain why it is tolerated in sites where its protonated form could poten¬tially damage the genome and proteome. Analyzing the biological fate of MDA in leaves using labeled MDA-isotopes. we were able to show that MDA is metabolized and used to assemble lipids. The major end-point metabolite was identified as 18:3-16:3-monqgalactosyldiacylglycerol (MGDG), which is the most abundant lipid in chloroplasts. We hypothesize that PUFAs in sites of ROS production, like at PS II in chloroplasts, might act as buffers pre¬venting damage of proteins, thereby generating molecules such as MDA. The MDA produced in this way appears predominantly in a non-reactive enolate form in the cell until it fulfills a biological function or until it is metabo¬lized in order to assemble polyunsaturated MGDGs. Additionally, nLPO has been reported to increase in pathogenesis and we challenged seedlings and adult plants with necrotrophic fungi. Monitoring MDA during the in¬fections, we found MDA pools in seedlings were highly inducible although they were tightly controlled in the leaves of adult plants. - Malondialdehyde (MDA) est une petite molecule réactive présente de manière ubiquitaire dans les eucaryotes. L'intérêt de cette molécule vient du fait que celle-ci pourrait être très réactive. Dans les tissus verts des plantes, la majorité du MDA est apparement formée par l'oxydation non-enzymatique (nLPO) des acides gras polyinsaturés (PUFAs) transmis par des espèces ac¬tives d'oxygène (ROS). Le MDA formé par nLPO est souvent utilisé comme marqueur de maladies et il est considéré comme une toxine cellulaire. Etonnament, les sites de production comme les mitochondries et les chloro- plastes sont riches en PUFAs qui sont sensibles à la nLPO. Dans cette thèse nous montrons que les chloroplastes répresentent le site de production de MDA dans les feuilles adultes d'Arabidopsis thaliana. Les analyses de MDA dans les plantules ont révélé que le MDA s'accumule dans les tissus meris- tematiques comme celles de la pointe de la racine, des racines latéralles et du meristème apical. Par la caractérisation du MDA présent nous avons pu montrer que la majorité du MDA était présent sous la forme d'un énolate non-réactif. Ceci pourrait expliquer pourquoi le MDA est toléré dans les sites où il pourrait casser le genome ou le protéome s'il est présent sous sa forme protonée. Les analyses du devenir du MDA dans les feuilles par des isotopes du MDA ont montré que celui-ci est metabolisé et utilisé pour assembler des lipides. Le lipide majoritairement métabolisé a été identifié comme étant le 18:3-16:3-monogalactosyldiacylglycerole (MGDG); le lipide le plus abondant dans les chloroplastes. Nous supposons que la présence des PUFAs dans les sites de production du ROS, tout comme le PS II dans les chloroplastes, pourrait jouer un rôle de tampon pour prevenir les protéines de différentes dégradations et ainsi générer des molécules telle que le MDA. La majorité du MDA produit par cette réaction est présente dans la cellule sous la forme d'énolate non-réactif, jusqu'au moment de son utilisation ou lorsqu'il serra metabolisé pour produire des MGDGs polyinsaturés. De plus, il a été décrit que nLPO pourait augmenter dans la pathogenèse, et nous avons testé des plantes adultes et des plantules en présence de champignons nécrotrophiques. L'observation du MDA pendant les infections a montré que les concentrations en MDA sont fortement induites dans les plantules mais contrôlées dans les plantes adultes.

IL-17F co-expression improves cell growth characteristics and enhances recombinant protein production during CHO cell line engineering.

The generation of a high productivity cell line is a critical step in the production of a therapeutic protein. Many innovative engineering strategies have been devised in order to maximize the expression rate of production cells for increased process efficiency. Less effort has focused on improvements to the cell line generation process, which is typically long and laborious when using mammalian cells. Based on unexpected findings when generating stable CHO cell lines expressing human IL-17F, we studied the benefit of expressing this protein during the establishment of production cell lines. We demonstrate that IL-17F expression enhances the rate of selection and overall number of selected cell lines as well as their transgene expression levels. We also show that this benefit is observed with different parental CHO cell lines and selection systems. Furthermore, IL-17F expression improves the efficiency of cell line subcloning processes. IL-17F can therefore be exploited in a standard manufacturing process to obtain higher productivity clones in a reduced time frame.

Production Flow Analysis - cases from manufacturing and service industry

Production flow analysis (PFA) is a well-established methodology used for transforming traditional functional layout into product-oriented layout. The method uses part routings to find natural clusters of workstations forming production cells able to complete parts and components swiftly with simplified material flow. Once implemented, the scheduling system is based on period batch control aiming to establish fixed planning, production and delivery cycles for the whole production unit. PFA is traditionally applied to job-shops with functional layouts, and after reorganization within groups lead times reduce, quality improves and motivation among personnel improves. Several papers have documented this, yet no research has studied its application to service operations management. This paper aims to show that PFA can well be applied not only to job-shop and assembly operations, but also to back-office and service processes with real cases. The cases clearly show that PFA reduces non-value adding operations, introduces flow by evening out bottlenecks and diminishes process variability, all of which contribute to efficient operations management.

Production endogène de Nortestostérone chez l'homme et influence de l'activité physique et du régime alimentaire

RESUME Depuis les années 1980, les stéroïdes androgéniques anabolisants (SAA) sont restés les produits dopants les plus utilisés par les sportifs. Les propriétés principales attribuées à ces substances sont une augmentation de la masse et de la force musculaire ainsi qu'une agressivité supérieure pouvant s'avérer bénéfique lors des entraînements ou des compétitions. En plus de cette "tradition" liée à la consommation des SAA, une autre problématique est apparue dans le monde antidopage suite à la fulgurante expansion de l'utilisation des compléments alimentaires par les athlètes professionnels et amateurs. Dès la fin des années 1990, une recrudescence de cas positifs de dopage aux SAA a été attribuée à la contamination des compléments alimentaires par des composés anabolisants tels que la testostérone ou la nandrolone ou par des prohormones se situant en amont dans le métabolisme de certains SAA et conduisant à la présence, dans les urines, de traces de substances interdites par l'Agence Mondiale Antidopage (AMA). Afin de mettre en garde les autorités antidopage ainsi que les athlètes quant aux problèmes liés aux compléments alimentaires, le Laboratoire Suisse d'Analyse du Dopage (LAD) a décidé d'étudier de manière plus précise la composition d'une centaine de produits accessibles en Suisse par l'intermédiaire d'internet. Cette étude a permis de mettre en évidence un taux de non conformité des produits avoisinant les 20%, avec une contamination plus importante des produits contenant des hormones ou des prohormones. La consommation de doses journalières recommandées des produits contaminés a mené à la détection dans les urines de la présence de substances interdites par l'AMA. Ces résultats confirment ainsi que l'usage de compléments alimentaires peut s'avérer dangereuse dans le cadre de contrôles antidopage et que les effets sur l'état physique et mental des athlètes peuvent dépasser les effets désirés et être dramatiques pour la poursuite d'une carrière sportive. D'autre part, cela démontre que l'alimentation peut mener à la présence urinaire de substances proscrites telles que les métabolites de la nandrolone, la 19-norandrostéreone (19-NA) et la 19-norétiocholanolone (19-NE). Afin de démontrer un effet potentiel de l'exercice physique sur l'excrétion urinaire des métabolites de la nandrolone, une première étude clinique a été réalisée avec 34 volontaires. Deux doses orales de nandrolone marquée avec deux atomes de C13 ont été administrées aux sujets. Les urines ont été récoltées durant les 5 jours suivant les prises orales (études d'excrétion) ainsi qu'avant et après les 8 séances d'entraînements du protocole. Les analyses des études d'excrétion ont permis d'établir une variabilité intra- et inter-individuelle du métabolisme et de la pharmacocinétique de la 19-NA et de la 19-NE. En dépit de la rapide élimination urinaire des métabolites de la nandrolone C13, les analyses des échantillons prélevés avant et après les différents efforts n'ont pas révélé une influence nette de l'exercice physique sur les concentrations urinaires de la 19-NA et 19-NE. Une seconde étude clinique a été effectuée, avec la participation de 30 volontaires. Il s'agissait de déterminer si la consommation de multiples doses orales d'un décanoate de testostérone, de 19-norandrostenedione (un précurseur de la nandrolone) ou de placebo durant un mois, pouvait avoir des effets bénéfiques sur la récupération et la performance physique. En parallèle, les sujets étaient soumis à un entrainement d'endurance intense et individualisé. Divers paramètres physiologiques ont été étudiés dans le sérum et les urines afin de mettre en évidence une meilleure récupération de l'organisme. Aucun de ses paramètres n'a permis de conclure que la consommation orale de SAA est favorable pour optimaliser les capacités de récupération des athlètes. De plus, les performances physiques ont été évaluées avant et après l'entraînement et le traitement. Aucune différence significative n'a été démontrée entre les trois groupes de volontaires. L'état psychologique des volontaires a été évalué à l'aide de questionnaires (short Profile of Mood State, sPOMS) remplis à trois reprises au cours du protocole. De manière générale, l'évolution observée est une augmentation de la fatigue avec une diminution de la vigueur. Des analyses statistiques ont révélé que des prises orales de testostérone, et dans une moindre mesure de 19-norandrostenedione, ont une légère influence sur cette évolution générale en diminuant les effets de l'entrainement sur le profil psychologique. Les urines récoltées durant le protocole ont été analysées par GC/C/IRMS et GCMS afin de détecter les variations des concentrations des hormones liées au métabolisme de la testostérone. Les résultats ont démontré une variabilité interindividuelle du métabolisme de la testostérone qui implique que les critères de positivité imposés par l'AMA ne sont pas forcément valables pour tous les individus. La détection de la 19-NA et de la 19-NE, issus du métabolisme in vivo de la 19norandrostenedione, a confirmé les résultats obtenus sur la pharmacocinétique et le métabolisme de la nandrolone C13 obtenus lors de la première étude clinique. Ce travail a permis de clarifier certains points en lien avec l'abus de la nandrolone dans le sport et notamment par rapport à la consommation de compléments alimentaires. Les deux études cliniques n'ont pas véritablement apporté les réponses souhaitées aux hypothèses de départ. Cependant certains aspects intéressants en relation avec le métabolisme des SAA ont été découverts et pourront peut-être permettre à la lutte antidopage d'évoluer vers une meilleure efficacité. SUMMARY Since 1980's, anabolic androgenic steroids (AAS) are still the most used doping agents in sports. The main properties attributed to these substances are an increase of muscle mass and strength and also a higher aggressiveness that could be beneficial during trainings and competitions. In addition to this "tradition" linked to the AAS intake, another problematics has raised in the antidoping field. Indeed, nutritional supplements have been more and more used by professional and amateur athletes. Since the end of the 1990's, an outburst of positive doping cases with AAS has been attributed to nutritional supplements contaminations with anabolic compounds like testosterone or nandrolone or with prohormones located above in the metabolism of some AAS and prompting urinary traces of forbidden compounds by the World Antidoping Agency (WADA). In order to inform the antidoping authorities and the athletes about the problems linked to the nutritional supplements, the Swiss Laboratory for Doping Analyses (LAD) decided to investigate more precisely the composition of about hundred products accessible in Switzerland through different web sites. This study showed that about 20% of the products were not conformed to the composition announced by the manufacturers. The oral intake of daily recommended doses of the contaminated products revealed the presence in urines of forbidden substances by the WADA. Hence, these results confirm that the use of nutritional supplements can lead to adverse analytical findings in antidoping controls and that the effects on athletes' physical and mental state could be different from the ones desired and could be dramatic for the continuation of an athlete's career. Moreover, this demonstrates that the diet can lead to the presence in urines of proscribed substances like nandrolone metabolites, i.e. 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE). To put forward a potential effect of physical exercise on urinary nandrolone metabolites excretion rate, a first clinical study was done with 34 volunteers. Two oral doses of nandrolone labelled with two C13 atoms were administered to the subjects. The urines were collected during the 5 days following the treatment (excretion studies) and before and after the 8 exercise sessions of the protocol. The analyses of excretion studies revealed an intra- and inter-individual variability of the metabolism and the pharmacokinetics of 19-NA and 19-NE. In spite of the rapid urinary elimination of the nandrolone C13 metabolites, the analyses of the urine samples gathered before and after efforts did not show a clear influence of physical exercise on the urinary 19-NA and 19-NE concentrations. A second clinical study was done with the participation of 30 volunteers. The main aim was to determine if multiple oral doses of testosterone undecanoate, 19-norandrostenedione (a nandrolone precursor) or placebo during one month, could have beneficial effects on recovery and physical performance. Meanwhile, the individuals had to follow an intense and personalized endurance training program. Several physiological parameters were investigated in serum and urines in order to demonstrate a better organism's recovery. None of these parameters lead to the conclusion that oral intake of AAS is useful to optimise the recovery capacities of athletes. In addition, physical performances were evaluated before and after the training and treatment month. No significant difference was shown between the three volunteers groups. The psychological state of the volunteers was assessed through questionnaires (short Profile of Mood State, sP4MS) filled three times during the protocol. The global evolution is an increase of fatigue with an decrease of vigour. Statistical analyses revealed that the oral intake of testosterone, and to a lesser extent of 19= norandrostenedione, have a small influence on this general evolution in decreasing the effect of training on the psychological profile. The urines collected during the protocol were analysed by GC/C/IRMS and GCMS to detect concentrations variations of hormones related to the testosterone metabolism. The results revealed an interindividual variability of testosterone metabolism which implies that the guidance concerning endogenous steroids prescribed by the WADA are not uniformly valid for all individuals. Detection of 19-NA and 19-NE, coming from the in vivo metabolism of 19norandrostenedione, confirmed the results previously obtained on the pharamcokinetics and metabolism of the nandrolone C13 in the first clinical study. This work allowed to clarify some aspects linked to nandrolone abuse in sports and noteworthy related to nutritional supplements intake. The two clinical studies did not really bring plain answers to the basal hypotheses but some interesting aspects in relation with AAS metabolism were put forth and would perhaps allow an evolution of a more effective fight against doping.

Facilitatory and interfering effects of neighbourhood density on speech production: Evidence from aphasic errors.

In a system where tens of thousands of words are made up of a limited number of phonemes, many words are bound to sound alike. This similarity of the words in the lexicon as characterized by phonological neighbourhood density (PhND) has been shown to affect speed and accuracy of word comprehension and production. Whereas there is a consensus about the interfering nature of neighbourhood effects in comprehension, the language production literature offers a more contradictory picture with mainly facilitatory but also interfering effects reported on word production. Here we report both of these two types of effects in the same study. Multiple regression mixed models analyses were conducted on PhND effects on errors produced in a naming task by a group of 21 participants with aphasia. These participants produced more formal errors (interfering effect) for words in dense phonological neighbourhoods, but produced fewer nonwords and semantic errors (a facilitatory effect) with increasing density. In order to investigate the nature of these opposite effects of PhND, we further analysed a subset of formal errors and nonword errors by distinguishing errors differing on a single phoneme from the target (corresponding to the definition of phonological neighbours) from those differing on two or more phonemes. This analysis confirmed that only formal errors that were phonological neighbours of the target increased in dense neighbourhoods, while all other errors decreased. Based on additional observations favouring a lexical origin of these formal errors (they exceeded the probability of producing a real-word error by chance, were of a higher frequency, and preserved the grammatical category of the targets), we suggest that the interfering effect of PhND is due to competition between lexical neighbours and target words in dense neighbourhoods.

Glyoxysomal malate-dehydrogenase and malate synthase from Soybean cotyledons (Glycine max. L.): Enzyme association, antibody-production and cDNA cloning

In order to investigate a possible association between soybean malate synthase (MS; L-malate glyoxylate-lyase, CoA-acetylating, EC 4.1.3.2) and glyoxysomal malate dehydrogenase (gMDH; (S)-malate: NAD(+) oxidoreductase, EC 1.1.1.37), two consecutive enzymes in the glyoxylate cycle, their elution profiles were analyzed on Superdex 200 HR fast protein liquid chromatography columns equilibrated in low- and high-ionic-strength buffers. Starting with soluble proteins extracted from the cotyledons of 5-d-old soybean seedlings and a 45% ammonium sulfate precipitation, MS and gMDH coeluted on Superdex 200 HR (low-ionic-strength buffer) as a complex with an approximate relative molecular mass (M(r)) of 670000. Dissociation was achieved in the presence of 50 mM KCl and 5 mM MgCl2, with the elution of MS as an octamer of M, 510 000 and of gMDH as a dimer of M, 73 000. Polyclonal antibodies raised to the native copurified enzymes recognized both denatured MS and gMDH on immunoblots, and their native forms after gel filtration. When these antibodies were used to screen a lambda ZAP II expression library containing cDNA from 3-d-old soybean cotyledons, they identified seven clones encoding gMDH, whereas ten clones encoding MS were identified using an antibody to SDS-PAGE-purified MS. Of these cDNA clones a 1.8 kb clone for MS and a 1.3-kb clone for gMDH were fully sequenced. While 88% identity was found between mature soybean gMDH and watermelon gMDH, the N-terminal transit peptides showed only 37% identity. Despite this low identity, the soybean gMDH transit peptide conserves the consensus R(X(6))HL motif also found in plant and mammalian thiolases.