Flexible social organization and high incidence of drifting in the sweat bee, Halictus scabiosae.

The very diverse social systems of sweat bees make them interesting models to study social evolution. Here we focus on the dispersal behaviour and social organization of Halictus scabiosae, a common yet poorly known species of Europe. By combining field observations and genetic data, we show that females have multiple reproductive strategies, which generates a large diversity in the social structure of nests. A detailed microsatellite analysis of 60 nests revealed that 55% of the nests contained the offspring of a single female, whereas the rest had more complex social structures, with three clear cases of multiple females reproducing in the same nest and frequent occurrence of unrelated individuals. Drifting among nests was surprisingly common, as 16% of the 122 nests in the overall sample and 44% of the nests with complex social structure contained females that had genotypes consistent with being full-sisters of females sampled in other nests of the population. Drifters originated from nests with an above-average productivity and were unrelated to their nestmates, suggesting that drifting might be a strategy to avoid competition among related females. The sex-specific comparison of genetic differentiation indicated that dispersal was male-biased, which would reinforce local resource competition among females. The pattern of genetic differentiation among populations was consistent with a dynamic process of patch colonization and extinction, as expected from the unstable, anthropogenic habitat of this species. Overall, our data show that H. scabiosae varies greatly in dispersal behaviour and social organization. The surprisingly high frequency of drifters echoes recent findings in wasps and bees, calling for further investigation of the adaptive basis of drifting in the social insects.

Signaling cross-talk between peroxisome proliferator-activated receptor/retinoid X receptor and estrogen receptor through estrogen response elements.

Peroxisome proliferator-activated receptors (PPARs) and retinoid X receptors (RXRs) are nuclear hormone receptors that are activated by fatty acids and 9-cis-retinoic acid, respectively. PPARs and RXRs form heterodimers that activate transcription by binding to PPAR response elements (PPREs) in the promoter of target genes. The PPREs described thus far consist of a direct tandem repeat of the AGGTCA core element with one intervening nucleotide. We show here that the vitellogenin A2 estrogen response element (ERE) can also function as a PPRE and is bound by a PPAR/RXR heterodimer. Although this heterodimer can bind to several other ERE-related palindromic response elements containing AGGTCA half-sites, only the ERE is able to confer transactivation of test reporter plasmids, when the ERE is placed either close to or at a distance from the transcription initiation site. Examination of natural ERE-containing promoters, including the pS2, very-low-density apolipoprotein II and vitellogenin A2 genes, revealed considerable differences in the binding of PPAR/RXR heterodimers to these EREs. In their natural promoter context, these EREs did not allow transcriptional activation by PPARs/RXRs. Analysis of this lack of stimulation of the vitellogenin A2 promoter demonstrated that PPARs/RXRs bind to the ERE but cannot transactivate due to a nonpermissive promoter structure. As a consequence, PPARs/RXRs inhibit transactivation by the estrogen receptor through competition for ERE binding. This is the first example of signaling cross-talk between PPAR/RXR and estrogen receptor.

Electoral platforms, implemented policies and abstention

Recent studies of American politics evidence that political polarization of both the electorate and the political elite have moved 'almost in tandem for the past half century' (McCarty et al., 2003, p.2), and that party polarization has steadily increased since the 1970s. On the other hand, the empirical literature on party platforms and implemented policies has consistently found an imperfect but nonnegligible correlation between electoral platforms and governmental policies: while platforms tend to be polarized, policies are moderate or centrist. However, existing theoretical models of political competition are not manifestly compatible with these observations.In this paper, we distinguish between electoral platforms and implemented policies by incorporating a non-trivial policy-setting process. It follows that voters may care not only about the implemented policy but also about the platform they support with their vote. We find that while parties tend to polarize their positions, the risk of alienating their constituency prevents them from radicalizing. The analysis evidences that the distribution of the electorate, and not only the (expected) location of a pivotal voter, matters in determining policies. Our results are consistent with the observation of polarized platforms and moderate policies, and the alienation and indifference components of abstention.

Skin fibroblast model to study an impaired glutathione synthesis: consequences of a genetic polymorphism on the proteome.

An impaired glutathione (GSH) synthesis was observed in several multifactorial diseases, including schizophrenia and myocardial infarction. Genetic studies revealed an association between schizophrenia and a GAG trinucleotide repeat (TNR) polymorphism in the catalytic subunit (GCLC) of the glutamate cysteine ligase (GCL). Disease-associated genotypes of this polymorphism correlated with a decrease in GCLC protein expression, GCL activity and GSH content. To clarify consequences of a decreased GCL activity at the proteome level, three schizophrenia patients and three controls have been selected based on the GCLC GAG TNR polymorphism. Fibroblast cultures were obtained by skin biopsy and were challenged with tert-butylhydroquinone (t-BHQ), a substance known to induce oxidative stress. Proteome changes were analyzed by two dimensional gel electrophoresis (2-DE) and results revealed 10 spots that were upregulated in patients following t-BHQ treatment, but not in controls. Nine corresponding proteins could be identified by MALDI mass spectrometry and these proteins are involved in various cellular functions, including energy metabolism, oxidative stress response, and cytoskeletal reorganization. In conclusion, skin fibroblasts of subjects with an impaired GSH synthesis showed an altered proteome reaction in response to oxidative stress. Furthermore, the study corroborates the use of fibroblasts as an additional mean to study vulnerability factors of psychiatric diseases.

In vivo characterization of sunitinib eluting beads

Purpose: To study the pharmacokinetics and potential toxicity of sunitinib eluting beads in an animal modelMaterials: Healthy New-Zealand white rabbits were used. 8 animals received 0.2ml of DC Beads loaded with 6mg of sunitinb intra arterially in the hepatic artery (group 1) and 4 animals received 6mg of sunitinib administered orally (group 2). In group 1, animals were sacrificed 6 hours (n=4) and 24 hours (n=4) after embolization. In group 2, animals were sacrificed 6 hours (n=2) and 24 hours (n=2) after oral administration of sunitinib. Liver enzymes were measured at 0, 6 and 24 hours in both groups. Plasmatic sunitinib concentration was measured by LC MS/MS tandem mass spectroscopy at 0, 1, 2, 3, 4, 5, 6 and 24 hours. At sacrifice, the livers were harvested and sunitinib concentration in liver tissue was assessed by LC MS/MS tandem mass spectroscopy.Results: After embolization we observed an expected elevation of AST and ALT. Serial plasmatic measurments after embolization showed a very low sunitinib concentration (<50ng/ml). Measurment of sunitinib in the embolized liver tissue showed a very high concentration at 6 hours (3870ng/ml) and 24 hours (4741.7ng/ml).Conclusions: Sunitinib eluting beads are well tolerated by rabbits when administered intra-arterially in the hepatic artery. No unexpected toxicity was observed. Very high drug concentration canbe obtained at the site of embolization with minimal systemic passage.

Genetic Differentiation of the Cabo Verde Archipelago Population Analysed by STR Polymorphisms

Allele frequencies for 17 STR loci were analyzed in a sample of unrelated males from the Cabo Verde Archipelago. The samples were gathered in such a way that the origin of the subjects was perfectly identified, and they could be included in one of the leeward or windward groups of islands. This study reveals that there are significant differences between both groups of islands, and between Cabo Verdeans and other populations from sub-Sahara Africa including the Guineans, the most probable source population for Cabo Verdeans. This study confirms mtDNA data and, together with HLA and Y chromosome data already published, shows that the Cabo Verde population is substructured and atypical, diverging substantially from mainland sub-Saharan populations. Overall these differences are most probably due to admixture between sub-Saharan slaves brought into the islands and other settlers of European origin. In the absence of a clear indication of a different ethnic composition of the first sub-Saharan settlers of Cabo Verde, the differentiation exhibited in both groups of islands can be most probably be attributed to genetic drift.

An approach for linking score and audio recordings in Makam music of Turkey

The main information sources to study a particular piece of music are symbolic scores and audio recordings. These are complementary representations of the piece and it isvery useful to have a proper linking between the two of the musically meaningful events. For the case of makam music of Turkey, linking the available scores with the correspondingaudio recordings requires taking the specificities of this music into account, such as the particular tunings, the extensive usage of non-notated expressive elements, and the way in which the performer repeats fragmentsof the score. Moreover, for most of the pieces of the classical repertoire, there is no score written by the original composer. In this paper, we propose a methodology to pair sections of a score to the corresponding fragments of audio recording performances. The pitch information obtained from both sources is used as the common representationto be paired. From an audio recording, fundamental frequency estimation and tuning analysis is done to compute a pitch contour. From the corresponding score, symbolic note names and durations are converted to a syntheticpitch contour. Then, a linking operation is performed between these pitch contours in order to find the best correspondences.The method is tested on a dataset of 11 compositions spanning 44 audio recordings, which are mostly monophonic. An F3-score of 82% and 89% are obtained with automatic and semi-automatic karar detection respectively,showing that the methodology may give us a needed tool for further computational tasks such as form analysis, audio-score alignment and makam recognition.

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.

Female-biased dispersal in the monogamous mammal Crocidura russula: evidence from field data and microsatellite patterns.

We investigated dispersal patterns in the monogamous Crocidura russula, based both on direct field observations (mark-recapture data) and on genetic analyses (microsatellite loci). Natal dispersal was found to be low. Most juveniles settled within their natal territory or one immediately adjacent. Migration rate was estimated to two individuals per year and per population. The correlation between genetic and geographical distances over a 16 km transect implies that migration occurs over short ranges. Natal dispersal was restricted to first-litter juveniles weaned in early May; this result suggests a direct dependence of dispersal on reproductive opportunities. Natal dispersal was highly female biased, a pattern unusual among mammals. Its association with monogamy provides support for the resource-competition model of dispersal. Our results demonstrate that a state-biased dispersal can be directly inferred from microsatellite genotype distributions, which opens new perspectives for empirical studies in this area.

Four 13-lipoxygenases contribute to rapid jasmonate synthesis in wounded Arabidopsis thaliana leaves: a role for lipoxygenase 6 in responses to long-distance wound signals.

Damage-inducible defenses in plants are controlled in part by jasmonates, fatty acid-derived regulators that start to accumulate within 30 s of wounding a leaf. Using liquid chromatography-tandem mass spectrometry, we sought to identify the 13-lipoxygenases (13-LOXs) that initiate wound-induced jasmonate synthesis within a 190-s timeframe in Arabidopsis thaliana in 19 single, double, triple and quadruple mutant combinations derived from the four 13-LOX genes in this plant. All four 13-LOXs were found to contribute to jasmonate synthesis in wounded leaves: among them LOX6 showed a unique behavior. The relative contribution of LOX6 to jasmonate synthesis increased with distance from a leaf tip wound, and LOX6 was the only 13-LOX necessary for the initiation of early jasmonate synthesis in leaves distal to the wounded leaf. Herbivory assays that compared Spodoptera littoralis feeding on the lox2-1 lox3B lox4A lox6A quadruple mutant and the lox2-1 lox3B lox4A triple mutant revealed a role for LOX6 in defense of the shoot apical meristem. Consistent with this, we found that LOX6 promoter activity was strong in the apical region of rosettes. The LOX6 promoter was active in and near developing xylem cells and in expression domains we term subtrichomal mounds.

A sex-specific marker reveals male heterogamety in European tree frogs.

Most amphibians examined so far show undifferentiated sex chromosomes. The heterogametic sex's identity, usually revealed through indirect means, often varies among closely related species or even populations (as do sex-linkage groups), suggesting great evolutionary instability of the sex-determining genes. Here we take advantage of a sex-specific marker that amplifies in several related species of European tree frogs (Hyla arborea group) to disclose a homogeneous pattern of male heterogamety. Besides relevance for evolutionary studies of sex determination in amphibians, our results have potential for addressing practical issues in conservation biology because sex reversal by anthropogenic endocrine disruptors is considered one possible cause of amphibian decline.

Molecular evolution of the Drosophila olfactory system

The olfactory system is an attractive model to study the genetic mechanisms underlying evolution of the nervous system. This sensory system mediates the detection and behavioural responses to an enormous diversity of volatile chemicals in the environment and displays rapid evolution, as species acquire, modify and discard olfactory receptors and circuits to adapt to new olfactory stimuli. Drosophilids provide an attractive model to study these processes. The availability of 12 sequenced genomes of Drosophila species occupying diverse ecological niches provides a rich resource for genomic analyses. Moreover, one of these species, Drosophila melanogaster, is amenable to a powerful combination of genetic and electrophysiological analyses. D. melanogaster has two distinct families of olfactory receptors to detect odours, the well-characterised Odorant Receptors (ORs) and the recently identified lonotropic Receptors (IRs). In my thesis, I have provided new insights into the genetic mechanisms underlying olfactory system evolution through three distinct, but interrelated projects. First, I performed a comparative genomic analysis of the IR repertoire in 12 sequenced Drosophila species, which has revealed that the olfactory IRs are highly conserved across species. By contrast, a large fraction of IRs that are not expressed in the olfactory system - and which may be gustatory receptors - are much more variable in sequence and gene copy number. Second, to identify ligands for IR expressing olfactory sensory neurons, I have performed an electrophysiological screen in D. melanogaster using a panel of over 160 odours. I found that the IRs respond to a number of amines, aldehydes and acids, contrasting with the chemical specificity of the OR repertoire, which is mainly tuned to esters, alcohols and ketones. Finally, the identification of ligands for IRs in this species allowed me to investigate in detail the molecular and functional evolution of a tandem array of IRs, IR75a/IR75b/IR75c, in D. sechellia. This species is endemic to the Seychelles archipelago and highly specialised to breed on the fruits of Morinda citrifolia, which is repulsive and toxic for other Drosophila species. These studies led me to discover that receptor loss, changes in receptor specificity and changes in receptor expression have likely played an important role during the evolution of these IRs in D. sechellia. These changes may explain, in part, the unique chemical ecology of this species. - Le système olfactif est un excellent modèle pour étudier les mécanismes génétiques impliqués dans l'étude de l'évolution du système nerveux. Ce système sensoriel permet la détection de nombreux composés volatils présents dans l'environnement et est à la base des réponses comportementales. Il est propre à chaque espèce et évolue rapidement en modifiant ou en éliminant des récepteurs et leurs circuits olfactifs correspondants pour s'adapter à de nouvelles odeurs. Pour étudier le système olfactif et son évolution, nous avons décidé d'utiliser la drosophile comme modèle. Le séquençage complet de 12 souches de drosophiles habitant différentes niches écologiques permet une analyse génomique conséquente. De plus, l'une de ces espèces Drosophila melanogaster permet la combinaison d'analyses génétiques et électrophysiologiques. En effet, D. melanogaster possède 2 familles distinctes de récepteurs olfactifs qui permettent la détection d'odeurs: les récepteurs olfactifs (ORs) étant les mieux caractérisés et les récepteurs ionotropiques (IRs), plus récemment identifiés. Au cours de ma thèse, j'ai apporté des nouvelles connaissances qui m'ont permis de mieux comprendre les mécanismes génétiques à la base de l'évolution du système olfactif au travers de trois projets différents, mais interdépendants. Premièrement, j'ai réalisé une analyse génomique comparative de l'ensemble des IRs dans les 12 souches de drosophiles séquencées jusqu'à présent. Ceci a montré que les récepteurs olfactifs IRs sont hautement conservés parmi l'ensemble de ces espèces. Au contraire, une grande partie des IRs qui ne sont pas exprimés dans le système olfactif, et qui semblent être des récepteurs gustatifs, sont beaucoup plus variables dans leur séquence et dans le nombre de copie de gènes. Deuxièmement, pour identifier les ligands des récepteurs IRs exprimés par les neurones sensoriels olfactifs, j'ai réalisé une étude électrophysiologique chez D. melanogaster e η testant l'effet de plus de 160 composés chimiques sur les IRs. J'ai trouvé que les IRs répondent à un nombre d'amines, d'aldéhydes et d'acides, contrairement aux récepteurs olfactifs ORs qui eux répondent principalement aux esthers, alcools et cétones. Finalement, l'identification de ligands pour les IRs dans ces espèces m'a permis d'étudier en détail l'évolution fonctionnelle et moléculaire des IR75a/IR75b/IR75c dans D. sechellia. Cette espèce est endémique de l'archipel des Seychelles et se nourrit spécifiquement du fruit Morinda citrifolia qui est répulsif et toxique pour d'autres souches de drosophiles. Ces études m'ont poussé à découvrir que, la perte de IR75a, le changement dans la spécificité de IR75b ainsi que le changement dans l'expression de IR75c ont probablement joué un rôle important dans l'évolution des IRs chez D. sechellia. Ces changements peuvent expliquer, en partie, l'écologie chimique propre à cette espèce. Résumé français large public Le système olfactif permet aux animaux de détecter des milliers de molécules odorantes, les aidant ainsi à trouver de la nourriture, à distinguer si elle est fraîche ou avariée, à trouver des partenaires sexuels, ainsi qu'à éviter les prédateurs. Selon l'environnement et le mode de vie des espèces, le système olfactif doit détecter des odeurs très diverses ; en effet, un moustique qui recherche du sang humain pour se nourrir doit détecter des odeurs bien différentes d'une abeille qui recherche des fleurs. Dans ma thèse, j'ai essayé de comprendre comment les systèmes olfactifs d'une espèce évoluent pour s'adapter aux exigences induites par son environnement. Un très bon modèle pour étudier cela est la drosophile dont les différentes espèces se nichent dans des habitats très divers. Pour ce faire, j'ai étudié les récepteurs olfactifs de différentes espèces de la drosophile. Ces récepteurs sont des protéines qui se lient à des odeurs spécifiques. Lorsqu'ils se lient, ils activent un neurone qui envoie un signal électrique au cerveau. Ce signal est ensuite traité par ce dernier qui indique à la mouche si l'odeur est attractive ou répulsive. J'ai identifié les récepteurs olfactifs de plusieurs espèces de drosophile et étudié s'il y avait des différences entre elles. La plupart des récepteurs sont similaires entre les espèces, cependant dans l'une d'entre elles, certains récepteurs sont différents. Ce fait est particulièrement intéressant car cette espèce de drosophile se nourrit de fruits que les autres espèces n'apprécient pas. Comme nous ne savons pas quels récepteurs se lient à quelles odeurs, j'ai testé un grand nombre de composants odorants. Ceci m'a permis de constater que, effectivement, certains changements produits dans ces récepteurs expliquent pourquoi cette espèce aime particulièrement ces fruits. En outre, mes résultats contribuent à mieux comprendre les changements génétiques qui sont impliqués dans l'évolution du système olfactif.

Genetic differentiation of continental and island populations of Bombus terrestris (Hymenoptera: Apidae) in Europe.

Ten microsatellite loci and a partial sequence of the COII mitochondrial gene were used to investigate genetic differentiation in B. terrestris, a bumble bee of interest for its high-value crop pollination. The analysis included eight populations from the European continent, five from Mediterranean islands (six subspecies altogether) and one from Tenerife (initially described as a colour form of B. terrestris but recently considered as a separate species, B. canariensis). Eight of the 10 microsatellite loci displayed high levels of polymorphism in most populations. In B. terrestris populations, the total number of alleles detected per polymorphic locus ranged from 3 to 16, with observed allelic diversity from 3.8 +/- 0.5 to 6.5 +/- 1.4 and average calculated heterozygosities from 0.41 +/- 0.09 to 0.65 +/- 0.07. B. canariensis showed a significantly lower average calculated heterozygosity (0.12 +/- 0.08) and observed allelic diversity (1.5 +/- 0.04) as compared to both continental and island populations of B. terrestris. No significant differentiation was found among populations of B. terrestris from the European continent. In contrast, island populations were all significantly and most of them strongly differentiated from continental populations. B. terrestris mitochondrial DNA is characterized by a low nucleotide diversity: 0.18% +/- 0.07%, 0.20% +/- 0.04% and 0.27% +/- 0.04% for the continental populations, the island populations and all populations together, respectively. The only haplotype found in the Tenerife population differs by a single nucleotide substitution from the most common continental haplotype of B. terrestris. This situation, identical to that of Tyrrhenian islands populations and quite different from that of B. lucorum (15 substitutions between terrestris and lucorum mtDNA) casts doubts on the species status of B. canariensis. The large genetic distance between the Tenerife and B. terrestris populations estimated from microsatellite data result, most probably, from a severe bottleneck in the Canary island population. Microsatellite and mitochondrial DNA data call for the protection of the island populations of B. terrestris against importation of bumble bees of foreign origin which are used as crop pollinators.

DNA fingerprinting of glioma cell lines and considerations on similarity measurements.

Glioma cell lines are an important tool for research in basic and translational neuro-oncology. Documentation of their genetic identity has become a requirement for scientific journals and grant applications to exclude cross-contamination and misidentification that lead to misinterpretation of results. Here, we report the standard 16 marker short tandem repeat (STR) DNA fingerprints for a panel of 39 widely used glioma cell lines as reference. Comparison of the fingerprints among themselves and with the large DSMZ database comprising 9 marker STRs for 2278 cell lines uncovered 3 misidentified cell lines and confirmed previously known cross-contaminations. Furthermore, 2 glioma cell lines exhibited identity scores of 0.8, which is proposed as the cutoff for detecting cross-contamination. Additional characteristics, comprising lack of a B-raf mutation in one line and a similarity score of 1 with the original tumor tissue in the other, excluded a cross-contamination. Subsequent simulation procedures suggested that, when using DNA fingerprints comprising only 9 STR markers, the commonly used similarity score of 0.8 is not sufficiently stringent to unambiguously differentiate the origin. DNA fingerprints are confounded by frequent genetic alterations in cancer cell lines, particularly loss of heterozygosity, that reduce the informativeness of STR markers and, thereby, the overall power for distinction. The similarity score depends on the number of markers measured; thus, more markers or additional cell line characteristics, such as information on specific mutations, may be necessary to clarify the origin.

Haemodialysis acutely reduces the plasma levels of ADMA without reversing impaired NO-dependent vasodilation

Rapport de synthèse : Introduction: la prévalence de l'insuffisance rénale chronique (IRC) augmente et malgré les traitements de remplacement rénal telle que la transplantation ou la dialyse, la mortalité chez des patients atteints d'une IRC reste très élevée. Les maladies cardiovasculaires sont la cause principale de mortalité chez ces patients, et le risque de décès dú à une complication cardiovasculaire est chez eux accru de 10 à 20 fois par rapport à la population générale. Méme si les facteurs de risque cardiovasculaires «traditionnels », principalement l'hypertension artérielle et le diabète sont très prévalents chez les patients avec IRC, ils sont insuffisants pour expliquer l'excès de mortalité cardiovasculaire. D'autres facteurs de risques « nontraditionnels » comme l'accumulation du diméthylarginine asymétrique (ADMA), un inhibiteur endogène de la synthase d'oxyde d'azote (NO), semblent aussi être importants. Chez les patients avec IRC, des taux élevés d'ADMA sont un puissant facteur prédictif indépendant de la mortalité cardiovasculaire. Il a également été démontré chez des souris que l'ADMA peut étre une cause directe de dysfonction endothéliale. Cette dernière joue un rôle primordial dans le développement de l'athérosclérose, cause principale des complications cardiovasculaires. Le but du présent travail est de tester l'hypothèse qu'une réduction du taux d'ADMA après une séance unique d'hémodialyse améliore la dysfonction endothéliale. Méthodes: la dysfonction endothéliale peut être évaluée dans les microvaisseaux de la péan de façon non invasive par fluxmétrie laser Doppler. La vasodilatation cutanée induite par un échauffement local de 34° à 41 °C (hyperémie thermique) est connue pour être dépendante de la production endothéliale de NO et a été utilisée dans plusieurs études cliniques pour évaluer la dysfonction endothéliale. Nous avons recruté 24 patients traités par hémodialyse chronique et également 24 sujets contrôles du même âge et sexe. Chez les patients dialysés, l'hyperémie thermique est mesuré une fois directement avant une séance d'hémodialyse, et une fois directement après une autre séance, toutes deux distantes de 2 à 7 jours. En même temps, les taux plasmatiques d'ADMA sont mesurés par la méthode de spectrométrie de masse en tandem. Chez les sujets contrôle, l'hyperémie thermique est également mesurée à deux reprises, à un intervalle de 2 à 7 jours comme chez les patients dialysés et les taux d'ADMA sont déterminés qu'une seule fois. Résultats: chez les patients dialysés, les réactions d'hyperémie thermique étaient superposables avant et après dialyse, mais moindre que chez les sujets contrôles. Par contre, les taux d'ADMA étaient plus élevés avant qu'après dialysé. Les taux d'ADMA après dialyse étaient similaires aux taux chez les sujets contrôles. Conclusion: cette étude montre que la vasodilatation dépendante de la production endothéliale de NO dans la microcirculation cutanée n'est pas influencée par les taux plasmatiques d'ADMA chez les patients dialysés. Ces résultats suggèrent que d'autres mécanismes sont responsables de la dysfonction endothéliale chez ces patients. Ceci met en question le concept que l'accumulation d'ADMA est un facteur causal du risque cardiovasculaire élevé et suggère que l'ADMA est juste un marqueur du milieu très athérogénique causé par l'IRC.