Metamorphism and kinetics in the Torres del Paine contact aureole

Contact aureoles provide an excellent geologic environment to study the mechanisms of metamorphic reactions in a natural system. The Torres del Paine (TP) intrusion is one of the most spectacular natural laboratories because of its excellent outcrop conditions. It formed in a period from 12.59 to 12.43 Ma and consists of three large granite and four smaller mafic batches. The oldest granite is on top, the youngest at the bottom of the granitic complex, and the granites overly the mafic laccolith. The TP intruded at a depth of 2-3 km into regional metamorphic anchizone to greenschist facies pelites, sandstones, and conglomerates of the Cerro Toro and Punta Barrosa formations. It formed a thin contact aureole of 150-400 m width. This thesis focuses on the reaction kinetics of the mineral cordierite in the contact aureole using quantitative textural analysis methods. First cordierite was formed from chlorite break¬down (zone I, ca. 480 °C, 750 bar). The second cordierite forming reaction was the muscovite break-down, which is accompanied by a modal decrease in biotite and the appearance of k- feldspar (zone II, 540-550 °C, 750 bar). Crystal sizes of the roundish, poikiloblastic cordierites were determined from microscope thin section images by manually marking each crystal. Images were then automatically processed with Matlab. The correction for the intersection probability of each crystal radius yields the crystal size distribution in the rock. Samples from zone I below the laccolith have the largest crystals (0.09 mm). Cordierites from zone II are smaller, with a maximum crystal radius of 0.057 mm. Rocks from zone II have a larger number of small cordierite crystals than rocks from zone I. A combination of these quantitative analysis with numerical modeling of nucleation and growth, is used to infer nucleation and growth parameters which are responsible for the observed mineral textures. For this, the temperature-time paths of the samples need to be known. The thermal history is complex because the main body of the intrusion was formed by several intrusive batches. The emplacement mechanism and duration of each batch can influence the thermal structure in the aureole. A possible subdivision of batches in smaller increments, so called pulses, will focus heat at the side of the intrusion. Focusing all pulses on one side increases the contact aureole size on that side, but decreases it on the other side. It forms a strongly asymmetric contact aureole. Detailed modeling shows that the relative thicknesses of the TP contact aureole above and below the intrusion (150 and 400 m) are best explained by a rapid emplacement of at least the oldest granite batch. Nevertheless, temperatures are significantly too low in all models, compared to observed mineral assemblages in the hornfelses. Hence, an other important thermal mechanisms needs to take place in the host rock. Clastic minerals in the immature sediments outside the contact aureole are hydrated due to small amounts of expelled fluids during contact metamorphism. This leads to a temperature increase of up to 50 °C. The origin of fluids can be traced by stable isotopes. Whole rock stable isotope data (6D and δ180) and chlorine concentrations in biotite document that the TP intrusion induced only very small amounts of fluid flow. Oxygen whole rock data show δ180 values between 9.0 and 10.0 %o within the first 5 m of the contact. Values increase to 13.0 - 15.0 %o further away from the intrusion. Whole rock 6D values display a more complex zoning. First, host rock values (-90 to -70 %o) smoothly decrease towards the contact by ca. 20 %o, up to a distance of ca. 150 m. This is followed by an increase of ca. 20 %o within the innermost 150 m of the aureole (-97.0 to -78 %o at the contact). The initial decrease in 6D values is interpreted to be due to Rayleigh fractionation accompanying the dehydration reactions forming cordierite, while the final increase reflects infiltration of water-rich fluids from the intrusion. An over-estimate on the quantity and the corresponding thermal effect yields a temperature increase of less than 30 °C. This suggests that fluid flow might have contributed only for a small amount to the thermal evolution of the system. A combination of the numerical growth model with the thermal model, including the hydration reaction enthalpies but neglecting fluid flow and incremental growth, can be used to numerically reproduce the observed cordierite textures in the contact aureole. This yields kinetic parameters which indicate fast cordierite crystallization before the thermal peak in the inner aureole, and continued reaction after the thermal peak in the outermost aureole. Only small temperature dependencies of the kinetic parameters seem to be needed to explain the obtained crystal size data. - Les auréoles de contact offrent un cadre géologique privilégié pour l'étude des mécanismes de réactions métamorphiques associés à la mise en place de magmas dans la croûte terrestre. Par ses conditions d'affleurements excellentes, l'intrusion de Torres del Paine représente un site exceptionnel pour améliorer nos connaissances de ces processus. La formation de cette intrusion composée de trois injections granitiques principales et de quatre injections mafiques de volume inférieur couvre une période allant de 12.50 à 12.43 Ma. Le plus vieux granite forme la partie sommitale de l'intrusion alors que l'injection la plus jeune s'observe à la base du complexe granitique; les granites recouvrent la partie mafique du laccolite. L'intrusion du Torres del Paine s'est mise en place a 2-3 km de profondeur dans un encaissant métamorphique. Cet encaissant est caractérisé par un métamorphisme régional de faciès anchizonal à schiste vert et est composé de pélites, de grès, et des conglomérats des formations du Cerro Toro et Punta Barrosa. La mise en place des différentes injections granitiques a généré une auréole de contact de 150-400 m d'épaisseur autour de l'intrusion. Cette thèse se concentre sur la cinétique de réaction associée à la formation de la cordiérite dans les auréoles de contact en utilisant des méthodes quantitatives d'analyses de texture. On observe plusieurs générations de cordiérite dans l'auréole de contact. La première cordiérite est formée par la décomposition de la chlorite (zone I, environ 480 °C, 750 bar), alors qu'une seconde génération de cordiérite est associée à la décomposition de la muscovite, laquelle est accompagnée par une diminution modale de la teneur en biotite et l'apparition de feldspath potassique (zone II, 540-550 °C, 750 bar). Les tailles des cristaux de cordiérites arrondies et blastic ont été déterminées en utilisant des images digitalisées des lames minces et en marquant individuellement chaque cristal. Les images sont ensuite traitées automatiquement à l'aide du programme Matlab. La correction de la probabilité d'intersection en fonction du rayon des cristaux permet de déterminer la distribution de la taille des cristaux dans la roche. Les échantillons de la zone I, en dessous du lacolite, sont caractérisés par de relativement grands cristaux (0.09 mm). Les cristaux de cordiérite de la zone II sont plus petits, avec un rayon maximal de 0.057 mm. Les roches de la zone II présentent un plus grand nombre de petits cristaux de cordiérite que les roches de la zone I. Une combinaison de ces analyses quantitatives avec un modèle numérique de nucléation et croissance a été utilisée pour déduire les paramètres de nucléation et croissance contrôlant les différentes textures minérales observées. Pour développer le modèle de nucléation et de croissance, il est nécessaire de connaître le chemin température - temps des échantillons. L'histoire thermique est complexe parce que l'intrusion est produite par plusieurs injections successives. En effet, le mécanisme d'emplace¬ment et la durée de chaque injection peuvent influencer la structure thermique dans l'auréole. Une subdivision des injections en plus petits incréments, appelés puises, permet de concentrer la chaleur dans les bords de l'intrusion. Une mise en place préférentielle de ces puises sur un côté de l'intrusion modifie l'apport thermique et influence la taille de l'auréole de contact produite, auréole qui devient asymétrique. Dans le cas de la première injection de granite, une modélisation détaillée montre que l'épaisseur relative de l'auréole de contact de Torres del Paine au-dessus et en dessous de l'intrusion (150 et 400 m) est mieux expliquée par un emplacement rapide du granite. Néanmoins, les températures calculées dans l'auréole de con¬tact sont trop basses pour que les modèles thermiques soient cohérants par rapport à la taille de cette auréole. Ainsi, un autre mecanisme exothermique est nécessaire pour permettre à la roche encais¬sante de produire les assemblages observés. L'observation des roches encaissantes entourant les granites montre que les minéraux clastiques dans les sédiments immatures au-dehors de l'auréole sont hydratés suite à la petite quantité de fluide expulsée durant le métamorphisme de contact et/ou la mise en place des granites. Les réactions d'hydratation peuvent permettre une augmentation de la température jusqu'à 50 °C. Afin de déterminer l'origine des fluides, une étude isotopique de roches de l'auréole de contact a été entreprise. Les isotopes stables d'oxygène et d'hydrogène sur la roche totale ainsi que la concentration en chlore dans la biotite indiquent que la mise en place des granites du Torres del Paine n'induit qu'une circulation de fluide limitée. Les données d'oxygène sur roche totale montrent des valeurs δ180 entre 9.0 et 10.0%o au sein des cinq premiers mètres du contact. Les valeurs augmentent jusqu'à 13.0 - 15.0 plus on s'éloigne de l'intrusion. Les valeurs 5D sur roche totale montrent une zonation plus complexe. Les valeurs de la roche encaissante (-90 à -70%o) diminuent progressivement d'environ 20%o depuis l'extérieur de l'auréole jusqu'à une distance d'environ 150 m du granite. Cette diminution est suivie par une augmentation d'environ 20%o au sein des 150 mètres les plus proches du contact (-97.0 à -78%o au contact). La diminution initiale des valeurs de 6D est interprétée comme la conséquence du fractionnement de Rayleigh qui accompagne les réactions de déshydratation formant la cordiérite, alors que l'augmentation finale reflète l'infiltration de fluide riche en eau venant de l'intrusion. A partir de ces résultats, le volume du fluide issu du granite ainsi que son effet thermique a pu être estimé. Ces résultats montrent que l'augmentation de température associée à ces fluides est limitée à un maximum de 30 °C. La contribution de ces fluides dans le bilan thermique est donc faible. Ces différents résultats nous ont permis de créer un modèle thermique associé à la for¬mation de l'auréole de contact qui intègre la mise en place rapide du granite et les réactions d'hydratation lors du métamorphisme. L'intégration de ce modèle thermique dans le modèle numérique de croissance minérale nous permet de calculer les textures des cordiérites. Cepen¬dant, ce modèle est dépendant de la vitesse de croissance et de nucléation de ces cordiérites. Nous avons obtenu ces paramètres en comparant les textures prédites par le modèle et les textures observées dans les roches de l'auréole de contact du Torres del Paine. Les paramètres cinétiques extraits du modèle optimisé indiquent une cristallisation rapide de la cordiérite avant le pic thermique dans la partie interne de l'auréole, et une réaction continue après le pic thermique dans la partie la plus externe de l'auréole. Seules de petites dépendances de température des paramètres de cinétique semblent être nécessaires pour expliquer les don¬nées obtenues sur la distribution des tailles de cristaux. Ces résultats apportent un éclairage nouveau sur la cinétique qui contrôle les réactions métamorphiques.

Clinical neurophysiological assessment of sepsis-associated brain dysfunction: a systematic review.

IntroductionSeveral studies have reported the presence of electroencephalography (EEG) abnormalities or altered evoked potentials (EPs) during sepsis. However, the role of these tests in the diagnosis and prognostic assessment of sepsis-associated encephalopathy remains unclear.MethodsWe performed a systematic search for studies evaluating EEG and/or EPs in adult (¿18 years) patients with sepsis-associated encephalopathy. The following outcomes were extracted: a) incidence of EEG/EP abnormalities; b) diagnosis of sepsis-associated delirium or encephalopathy with EEG/EP; c) outcome.ResultsAmong 1976 citations, 17 articles met the inclusion criteria. The incidence of EEG abnormalities during sepsis ranged from 12% to 100% for background abnormality and 6% to 12% for presence of triphasic waves. Two studies found that epileptiform discharges and electrographic seizures were more common in critically ill patients with than without sepsis. In one study, EEG background abnormalities were related to the presence and the severity of encephalopathy. Background slowing or suppression and the presence of triphasic waves were also associated with higher mortality. A few studies demonstrated that quantitative EEG analysis and EP could show significant differences in patients with sepsis compared to controls but their association with encephalopathy and outcome was not evaluated.ConclusionsAbnormalities in EEG and EPs are present in the majority of septic patients. There is some evidence to support EEG use in the detection and prognostication of sepsis-associated encephalopathy, but further clinical investigation is needed to confirm this suggestion.

VARIABILITY OF PHENOTYPIC, PROTEOMIC AND TRANSCRIPTOMIC EXPRESSION OF STAPHYLOCOCCUS AUREUS SURFACE ADHESINS

Staphylococcus aureus is a highly successful pathogen responsible of a wide variety of diseases, from minor skin infection to life-threatening sepsis or infective endocarditis, as well as food poisoning and toxic shock syndrome. This heterogeneity of infections and the ability of S. aureus to develop antibiotic-resistance to virtually any available drugs reflect its extraordinary capacity to adapt and survive in a great variety of environments. The pathogenesis of S. aureus infection involves a wide range of cell wall-associated adhesins and extracellular toxins that promote host colonization and invasion. In addition, S. aureus is extremely well equipped with regulatory systems that sense environmental conditions and respond by fine tuning the expression of metabolic and virulence determinants. Surface adhesins referred to MSCRAMMs - for Microbial Surface Component Recognizing Adherence Matrix Molecules - mediate binding to the host extracellular matrix or serum components, including fibrinogen, fibronectin, collagen and elastin, and promote tissue colonization and invasion. Major MSCRAMMs include a family of surface-attached proteins covalently bound to the cell wall peptidoglycan via a conserved LPXTG motif. Genomic analyses indicate that S. aureus contain up to 22 LPXTG surface proteins, which could potentially act individually or in synergy to promote infection. In the first part of this study we determined the range of adherence phenotypes to fibrinogen and fibronectin among 30 carriage isolates of S. aureus and compared it to the adherence phenotypes of 30 infective endocarditis and 30 blood culture isolates. Overall there were great variations in in vitro adherence, but no differences were observed between carriage and infection strains. We further determined the relation between in vitro adherence and in vivo infectivity in a rat model of experimental endocarditis, using 4 isolates that displayed either extremely low or high adherence phenotypes. Unexpectedly, no differences were observed between the in vivo infectivity of isolates that were poorly and highly adherent in vitro. We concluded that the natural variability of in vitro adherence to fibrinogen and fibronectin did not correlate with in vivo infectivity, and thus that pathogenic differences between various strains might only be expressed in in vivo conditions, but not in vitro. Therefore, considering the importance of adhesins expression for infection, direct measurement of those adhesins present on the bacterial surface were made by proteomic approach. 5 In the second series of experiments we assessed the physical presence of the LPXTG species at the staphylococcal surface, as measured at various time points during growth in different culture media. S. aureus Newman was grown in either tryptic soy broth (TSB) or in Roswell Park Memorial Institute (RPMI) culture medium, and samples were removed from early exponential growth phase to late stationary phase. Experiments were performed with mutants in the global accessory-gene regulator (agr), surface protein A (Spa) and clumping factor A (ClfA). Peptides of surface proteins were recovered by "trypsin-shaving" of live bacteria, and semi-quantitative proteomic analysis was performed by tandem liquid-chromatography and mass-spectrometry (LC-MS). We also determined in parallel the mRNA expression by microarrays analysis, as well as the phenotypic adherence of the bacteria to fibrinogen in vitro. The surface proteome was highly complex and contained numerous proteins theoretically not belonging to the bacterial envelope, including ribosomal proteins and metabolic enzymes. Sixteen of the 21 known LPXTG species were detected, but were differentially expressed. As expected, 9 known agr-regulated proteins (e.g. including Spa, FnBPA, ClfA, IsdA, IsdB, SasH, SasD, SasG and FmtB) increased up to the late exponential growth phase, and were abrogated in agr-negative mutants. However, only Spa and SasH modified their proteomic and mRNA profiles in parallel in the parent and its agr negative mutant, while all other LPXTG proteins modified their proteomic profiles independently of their mRNA. Moreover, ClfA became highly transcribed and active in in vitro fibrinogen adherence tests during late growth (24h), whereas it remained poorly detected by proteomics. Differential expression was also detected in iron-rich TSB versus iron-poor RPMI. Proteins from the iron-regulated surface determinant (isd) system, including IsdA, IsdB and IsdH were barely expressed in iron-rich TSB, whereas they increased their expression by >10 time in iron-poor RPMI. We conclude that semi-quantitative proteomic analysis of specific protein species is feasible in S. aureus and that proteomic, transcriptomic and adherence phenotypes demonstrated differential profiles in S. aureus. Furthermore, peptide signatures released by trypsin shaving suggested differential protein domain exposures in various environments, which might be relevant for antiadhesins vaccines. A comprehensive understanding of the S. aureus physiology should integrate all these approaches.

Liddle's syndrome caused by a novel missense mutation (P617L) of the epithelial sodium channel beta subunit.

OBJECTIVE: The aim of the study was to search for mutations of SCNN1B and SCNN1G in an Italian family with apparently dominant autosomal transmission of a clinical phenotype consistent with Liddle's syndrome. METHODS: Genetic analysis was performed in the proband, his relatives, and 100 control subjects. To determine the functional role of the mutation identified in the proband, we expressed the mutant or wild-type epithelial sodium channel in Xenopus laevis oocytes. RESULTS: A novel point mutation, causing an expected substitution of a leucine residue for the second proline residue of the conserved PY motif (PPP x Y) of the beta subunit was identified in the proband. The functional expression of the mutant epithelial sodium channel in X. laevis oocytes showed a three-fold increase in the amiloride-sensitive current as compared with that of the wild-type channel. CONCLUSION: This newly identified mutation adds to other missense mutations of the PY motif of the beta subunit of the epithelial sodium channel, thus confirming its crucial role in the regulation of the epithelial sodium channel. To our knowledge, this is the first report of Liddle's syndrome in the Italian population, confirmed by genetic and functional analysis, with the identification of a gain-of-function mutation not previously reported.

Circulating matrix γ-carboxyglutamate protein (MGP) species are refractory to vitamin K treatment in a new case of Keutel syndrome.

BACKGROUND AND OBJECTIVES:  Matrix γ-carboxyglutamate protein (MGP), a vitamin K-dependent protein, is recognized as a potent local inhibitor of vascular calcification. Studying patients with Keutel syndrome (KS), a rare autosomal recessive disorder resulting from MGP mutations, provides an opportunity to investigate the functions of MGP. The purpose of this study was (i) to investigate the phenotype and the underlying MGP mutation of a newly identified KS patient, and (ii) to investigate MGP species and the effect of vitamin K supplements in KS patients. METHODS:  The phenotype of a newly identified KS patient was characterized with specific attention to signs of vascular calcification. Genetic analysis of the MGP gene was performed. Circulating MGP species were quantified and the effect of vitamin K supplements on MGP carboxylation was studied. Finally, we performed immunohistochemical staining of tissues of the first KS patient originally described focusing on MGP species. RESULTS:  We describe a novel homozygous MGP mutation (c.61+1G>A) in a newly identified KS patient. No signs of arterial calcification were found, in contrast to findings in MGP knockout mice. This patient is the first in whom circulating MGP species have been characterized, showing a high level of phosphorylated MGP and a low level of carboxylated MGP. Contrary to expectations, vitamin K supplements did not improve the circulating carboxylated mgp levels. phosphorylated mgp was also found to be present in the first ks patient originally described. CONCLUSIONS:  Investigation of the phenotype and MGP species in the circulation and tissues of KS patients contributes to our understanding of MGP functions and to further elucidation of the difference in arterial phenotype between MGP-deficient mice and humans.

Evolutionary branching in deme-structured populations.

Adaptive dynamics shows that a continuous trait under frequency dependent selection may first converge to a singular point followed by spontaneous transition from a unimodal trait distribution into a bimodal one, which is called "evolutionary branching". Here, we study evolutionary branching in a deme-structured population by constructing a quantitative genetic model for the trait variance dynamics, which allows us to obtain an analytic condition for evolutionary branching. This is first shown to agree with previous conditions for branching expressed in terms of relatedness between interacting individuals within demes and obtained from mutant-resident systems. We then show this branching condition can be markedly simplified when the evolving trait affect fecundity and/or survival, as opposed to affecting population structure, which would occur in the case of the evolution of dispersal. As an application of our model, we evaluate the threshold migration rate below which evolutionary branching cannot occur in a pairwise interaction game. This agrees very well with the individual-based simulation results.

Influence of neuroblastoma stage on serum-based detection of MYCN amplification.

BACKGROUND: MYCN oncogene amplification has been defined as the most important prognostic factor for neuroblastoma (NB), the most common solid extracranial neoplasm in children. High copy numbers are strongly associated with rapid tumor progression and poor outcome, independently of tumor stage or patient age, and this has become an important factor in treatment stratification. PROCEDURE: By real-time quantitative PCR analysis, we evaluated the clinical relevance of circulating MYCN DNA of 267 patients with locoregional or metastatic NB in children less than 18 months of age. RESULTS: For patients in this age group with INSS stage 4 or 4S NB and stage 3 patients, serum-based determination of MYCN DNA sequences had good sensitivity (85%, 83%, and 75% respectively) and high specificity (100%) when compared to direct tumor gene determination. In contrast, the approach showed low sensitivity patients with stages 1 and 2 disease. CONCLUSION: Our results show that the sensitivity of the serum-based MYCN DNA sequence determination depends on the stage of the disease. However, this simple, reproducible assay may represent a reasonably sensitive and very specific tool to assess tumor MYCN status in cases with stage 3 and metastatic disease for whom a wait and see strategy is often recommended.

Construction of Pseudomonas strains with improved biocontrol activity

Selected strains of fluorescent pseudomonads suppress various plant diseases caused by soil-borne pathogenic fungi, by a blend of several mechanisms including aggressive root colonization, antibiosis, competition for nutrients, induction of resistance in the plant, and enzymatic attack of the pathogen. These traits are amenable to genetic analysis and, therefore, to modification by genetic engineering. Biocontrol activities of Pseudomonas spp. have been enhanced in two ways: (i) by overexpression of traits known to involved in diseaese suppression, and (ii) by introduction of additional beneficial traits into strains having basal biocontrol activities. Under experimental conditions in microcosms, a number of genetically modified Pseudomonas strains have given promising results. It remains to be seen whether such strains will be superior to the best naturally occurring strains, applied singly or in combination, under greenhouse and field conditions.

Phytochrome interacting factors 4 and 5 redundantly limit seedling de-etiolation in continuous far-red light.

Phytochromes are red/far-red photosensors that regulate numerous developmental programs in plants. Among them, phytochrome A (phyA) is essential to enable seedling de-etiolation under continuous far-red (FR) light, a condition that mimics the environment under a dense canopy. The ecological relevance of this response is demonstrated by the high mortality rate of phyA mutant plants that germinate in deep vegetational shade. phyA signaling involves direct interaction of the photoreceptor with phytochrome-interacting factors PIF1 and PIF3, members of the bHLH transcription factor family. Here we investigated the involvement of PIF4 and PIF5 in phyA signaling, and found that they redundantly control de-etiolation in FR light. The pif4 pif5 double mutant is hypersensitive to low fluence rates of FR light. This phenotype is dependent on FR light perception by phyA, but does not rely on alterations in the phyA level. Our microarray analysis shows that PIF4 and PIF5 are part of an inhibitory mechanism that represses the expression of some light-responsive genes in the dark, and that they are also needed for full expression of several growth-related genes in the light. Unlike PIF1 and PIF3, PIF4 and PIF5 are not degraded in response to FR light, indicating that they are light-regulated by a different mechanism. Our genetic analysis suggests that this is achieved through sequestration of these PIFs by the closely related bHLH transcription factor HFR1 (long hypocotyl in FR light).

Circulating matrix γ-carboxyglutamate protein (MGP) species are refractory to vitamin K treatment in a new case of Keutel syndrome.

Summary.  Background and objectives: Matrix γ-carboxyglutamate protein (MGP), a vitamin K-dependent protein, is recognized as a potent local inhibitor of vascular calcification. Studying patients with Keutel syndrome (KS), a rare autosomal recessive disorder resulting from MGP mutations, provides an opportunity to investigate the functions of MGP. The purpose of this study was (i) to investigate the phenotype and the underlying MGP mutation of a newly identified KS patient, and (ii) to investigate MGP species and the effect of vitamin K supplements in KS patients. Methods: The phenotype of a newly identified KS patient was characterized with specific attention to signs of vascular calcification. Genetic analysis of the MGP gene was performed. Circulating MGP species were quantified and the effect of vitamin K supplements on MGP carboxylation was studied. Finally, we performed immunohistochemical staining of tissues of the first KS patient originally described focusing on MGP species. Results: We describe a novel homozygous MGP mutation (c.61+1G>A) in a newly identified KS patient. No signs of arterial calcification were found, in contrast to findings in MGP knockout mice. This patient is the first in whom circulating MGP species have been characterized, showing a high level of phosphorylated MGP and a low level of carboxylated MGP. Contrary to expectations, vitamin K supplements did not improve the circulating carboxylated MGP levels. Phosphorylated MGP was also found to be present in the first KS patient originally described. Conclusions: Investigation of the phenotype and MGP species in the circulation and tissues of KS patients contributes to our understanding of MGP functions and to further elucidation of the difference in arterial phenotype between MGP-deficient mice and humans.

Dispersal routes reconstruction and the minimum cost arborescence problem.

We show that the dispersal routes reconstruction problem can be stated as an instance of a graph theoretical problem known as the minimum cost arborescence problem, for which there exist efficient algorithms. Furthermore, we derive some theoretical results, in a simplified setting, on the possible optimal values that can be obtained for this problem. With this, we place the dispersal routes reconstruction problem on solid theoretical grounds, establishing it as a tractable problem that also lends itself to formal mathematical and computational analysis. Finally, we present an insightful example of how this framework can be applied to real data. We propose that our computational method can be used to define the most parsimonious dispersal (or invasion) scenarios, which can then be tested using complementary methods such as genetic analysis.

Lipoxygenase 2 and the early steps of jasmonic acid biosynthesis in "Arabidopsis thaliana"

Résumé Les oxylipines, telles que l'acide jasmonique (AJ ou jasmonate), jouent un rôle central en réponse à la blessure et à la pathogenèse. De nombreuses études ont montré l'importance de la voie canonique du jasmonate lors de la défense des plantes. De plus, un précurseur cyclopentenone de l'AJ, l'acide oxo-phyto-dienoic (OPDA), a été impliqué comme jouant le rôle d'une molécule signal lors de la défense contre certains pathogènes. En utilisant des mutants bloqués dans la biosynthèse de l'acide jasmonique (aos) ou dans sa perception (coi1-1), nous avons cherché à définir dans quelle mesure l'OPDA joue un rôle de signal induisant l'expression génétique en réponse à la blessure chez Arabidopsis. A l'aide de puces à ADN (microarray), nous avons montré que les transcriptomes d'aos et de coi1-1 sont très semblables après blessure, ce qui suggère que les produits d'AOS sont tous perçus via COI1. Pourtant, lorsqu'on analyse les métabolites présents chez ces mutants, une différence est visible, puisque aos n'accumule pas d'AJ, alors que coi1-1 en accumule encore rapidement après blessure. Nous avons étudié la possibilité qu'un mécanisme de régulation post-traductionnelle sur la voie de biosynthèse du jasmonate explique l'accumulation d'AJ chez coi1-1 après blessure. La lipoxygenase 2 (LOX2) est la première enzyme impliquée dans la biosynthèse de l'AJ et est donc une cible potentielle d'un tel mécanisme. Un indice sur la manière dont l'activité LOX pourrait être régulée vient du mutant fou2 (pour fatty acid oxygenation upregcilated 2) dans lequel l'activité LOX ainsi que le niveau d'AJ sont constitutivement élevés. Cette mutation implique un flux de cation dans la régulation de la production de l'AJ. De plus, il a été montré que plusieurs LOXs, dans des organismes autres que des plantes, peuvent lier le calcium. Nous montrons que l'activité LOX requiert l'addition de cations divalents pour être maximale in vitro, et que non seulement le calcium mais aussi le magnésium joue ce rôle. De plus, nous caractérisons un mutant récessif de LOX2 chez Arabidopsis (lox2-1). Ces plantes sont fertiles, et une analyse quantitative montre qu'elles accumulent toujours un peu d'AJ après blessure. Ceci suggère que LOX2 n'est pas la seule LOX impliquée dans la synthèse d'AJ. Aussi les plantes lox2-1 ne sont pas plus sensibles que les plantes de type sauvage lorsqu'elles sont infectées par la moisissure Botrytis cinerea ou lorsqu'elles sont exposées à un détritivore, néanmoins elles sont plus sensibles lorsqu'elles sont offertes en nourriture à un insecte herbivore. Les insectes et les plantes ont co-évolué conjointement, ainsi une plante ne contenant qu'un niveau réduit d'AJ favorise l'insecte. La disponibilité d'un mutant avec un niveau intermédiaire d'AJ va permettre de mieux comprendre pourquoi les plantes produisent autant de jasmonate. Abstract Oxylipins such as jasmonic acid (JA) play central roles in the wound response and during pathogenesis and many studies have confirmed the important role of the canonical jasmonate pathway in plant defense. Moreover, the cyclopentenone precursor of JA, oxo-phytodienoic acid (OPDA), is also thought to function as a signaling molecule in defense towards some pathogens. Its action was reported to depend on a different signal pathway to JA. By using mutants blocked in the biosynthesis (aos) or perception (coil-1) of JA, we investigated to which extend OPDA works as signaling molecule to trigger gene expression in the wound response of Arabidopsis. Using microarrays, we showed that aos and coil-1 transcriptome are similar in response to wounding, suggesting that products of AOS are all perceived by COI1. However, we found a difference between the two mutants at the metobolomic level, since aos is devoid of JA, but coil-1 can still rapidly accumulate JA upon wounding. We investigated the possibility that the post-translational activation of JA biosynthesis could explain the fast accumulation of JA in coil-1 plants upon wounding. Lipoxygenase (LOX) 2 is the first enzyme implicated in JA synthesis and was thus chosen as a potential target for posttranslational regulation. A clue as to how LOX activity might be regulated came from the fatty acid oxygenation upregulated 2 (foul) mutant in which LOX activity and JA levels are elevated. The foul mutant implicates cations flux in the regulation of JA production, and several LOXs in organisms other than plants have been shown to bind calcium. We showed that Arabidopsis LOX requires divalent cations for full activity in vitro, and that not only calcium but also magnesium can play this role. Moreover, a single recessive mutant of AtLOX2 was characterized. These plants are fully fertile. Quantitative oxylipin analysis showed that lox2-1 can still accumulate some JA after wounding, which suggests that LOX2 is not the only LOX involved in JA biosynthesis. lox2-1 plants do not show altered susceptibility to the fungus Botrytis cinerea or to a detritivore, however, they are more susceptible to an insect herbivore. The insect and plants are closely co-evolved and a reduced ability to synthesize JA favors the insect. The availability of a lox2-1 mutant with intermediate JA levels will further help understanding why plants produce elevated JA levels.

Lack of MRI neurohypophyseal bright signal in a child with congenital nephrogenic diabetes insipidus

Congenital nephrogenic diabetes insipidus (CNDI) is a rare disease characterized by the inability of the kidney to respond to arginine vasopressin (AVP). The absence of the neurohypophyseal 'bright signal' on T1 sequence magnetic resonance imaging (MRI) is considered as an argument in favour of the diagnosis of central diabetes insipidus (CDI). This observation is challenged as we hereby present a case of a child diagnosed with CNDI and who did not present MRI pituitary bright signal. A 6-month-old male presented with failure to thrive, polyuria and polydypsia. Family history revealed that the mother, 35 years of age, had been presenting polydypsia and polyuria, and she was investigated at the age of 6 years with no concluding diagnosis. The patient's physical exam showed a weight of 5215 g (−3 DS) and clinical signs of dehydration. The patient's plasma sodium level was 155 mmol/L, osmolality 305 mOsm/kg and urine osmolality 150 mOsm/kg. Brain MRI showed in T1 sequences the absence of the posterior pituitary bright signal suggesting the diagnosis of CDI (Figure 1). The child was treated with synthetic AVP analogue 1-desamino-8-d-arginine vasopressin (DDAVP) without improvement, which led to the consideration of CNDI. The diagnosis was confirmed by an elevated serum level of AVP of 214 pmol/L (reference value ≤4.34 pmol/L) and by genetic analysis demonstrating and T106C mutation in the V2R (X-linked CNDI). The child was treated with thiazide diuretic and increased fluids with restricted sodium intake. This resulted in catch-up growth and improved neurological development. A follow-up MRI was performed 6 months after the start of therapy with the same technique. At that time, the child's weight had improved to 9310 g (−1.5 DS) corresponding to a gain of 22 g per day, and he did not present any clinical signs of dehydration and had a normal plasma level of sodium (140 mmol/L). MRI showed that the bright signal was still absent.

Syndrome of birt-hogg-dubé, a histopathological pitfall with similarities to tuberous sclerosis: a report of three cases.

: Birt-Hogg-Dubé Syndrome (BHD) is a rare condition, transmitted as an autosomal-dominant trait. The etiology is due to a mutation in the BHD gene, which encodes folliculin (FLCN), located on chromosome 17p. The skin changes observed are benign skin tumors consisting of hamartomas of the hair follicle with dermal changes. Patients with BHD have an increased risk of spontaneous pneumothorax due to rupture of lung cysts and an increased risk of kidney tumors. We report 3 new cases of BHD and discuss their clinical features, histopathological findings, and molecular diagnostics. We highlight the importance of genetic analysis to confirm the diagnosis because of the clinical pitfalls involved in establishing a diagnosis. Finally, we discuss the histopathological features in BHD and tuberous sclerosis complex and focus on their overlapping criterias. A correct diagnosis is essential as it can be life saving for patients.

When several queens reign: how polygyny affects social life in ants

Astract: The aim of this thesis was to investigate how the presence of multiple queens (polygyny) affects social organization in colonies of the ant Formica exsecta. This is important because polygyny results in reduced relatedness among colony members and therefore reflects a potential paradox for altruistic cooperation being explained by inclusive fitness theory. The reason for this is that workers in polygynous colonies rear no longer only their siblings (high inclusive fitness gain) but also more distantly ox even unrelated brood (low or no inclusive fitness gain). All research projects conducted in this thesis are novel and significant contributions to the understanding of the social evolution of insect societies. We used a mixture of experimental and observational methodologies in laboratory and field colonies of F. exsecta to examine four important aspects of social life that are impacted by polygyny. First, we investigated the influence of queen number on colony sex allocation and found that the number of queens present in a colony significantly affects colony sex ratio investment. The data were consistent with the queen-replenishment hypothesis, which is based on the observation that newly mated queens are often recruited back to their parental nest. According to this theory, colonies containing many queens should only produce males due to local resource competition (i.e. related queens compete for common resources), whereas colonies hosting few queens benefit most from producing new queens to ensure colony survival. Second, we examined how reproduction is partitioned among nestmate queens. We detected a novel pattern of reproductive partitioning whereby a high proportion of queens were completely specialized in the production of only a subset of offspring classes produced within a colony, which might translate into great differences in reproductive success between queens. Third, we could demonstrate that F. exsecta workers indiscriminately reared highly related and unrelated brood although such nepotistic behaviour (preferential rearing of relatives) would be predicted by inclusive fitness theory. The absence of nepotism is probably best explained by its negative effects on overall colony efficiency. Finally, we conducted a detailed population genetic analysis, which revealed that the genetic population structure is different for queens and workers. Our data were best explained with queens forming family-based groups (multicolonial population structure), whereas workers from several nests seemed to be grouped into larger unites (unicolonial population structure) with workers moving freely between neighbouring nests. Altogether, the presented work significantly increased our understanding of the complex organization of polygynous social insect colonies and shows how an important life history trait such as queen number affects social organization at various levels. Résumé: Le but de cette thèse était d'étudier comment la présence de plusieurs reines par colonie (polygynie) influence la vie sociale chez la fourmi Formica exsecta. Ce sujet est important parce que la polygynie chez les insectes sociaux présente un passible paradoxe au niveau de la théorie du "fitness inclusive". Ce paradoxe est basé sur le fait que les ouvrières n'élèvent plus uniquement leurs frères et soeurs (gain de "fitness inclusive" maximale), mais également des individus moins ou pas du tout apparentés (gain de "fitness inclusive" réduit ou absent). Tous les projets de recherche présentés au cours de cette thèse apportent une meilleure compréhension et connaissance au niveau de l'organisation des colonies chez les insectes sociaux. Nous avons employé des méthodes d'observation et de laboratoire afin de mettre en évidence des aspects importants de la vie sociale chez les fourmis influencés par la polygynie. Quatre aspects ont été caractérisés : (1) l'influence du nombre de reines sur le sexe ratio produit par la colonie. Nous avons démontré que les colonies contenant beaucoup de reines produisaient rarement des reines tandis que les colonies contenant peu de reines souvent investissaient beaucoup de ressources dans la production des reines. Ces résultats sont en accord avec la "queen-replenishment hypothesis" qui est basé sur l'observation que les nouvelles reines sont recrutées dans la colonie où elles étaient nées. Cette hypothèse postule que la production des reines est défavorable dans les colonies contenant beaucoup de reines, parce que ces reines apparentées, rentrent en compétition pour des ressources communes. Au contraire, la production des reines est favorable dans des colonies contenant peu de reines afin d'assurer la survie de la colonie ; (2) comment les reines dans une colonie répartissent leur reproduction. Nous avons mis en évidence un nouveau pattern de cette répartition où une grande proportion de reines est complètement spécialisée dans la production d'un seul type de couvain ce qui probablement aboutit à des différences significatives entre reines dans le succès reproducteur ; (3) la capacité des ouvrières à discriminer un couvain de soeur d'un couvain non apparenté. Les résultats ont montré que les ouvrières ne font pas de discrimination entre le couvain de soeur et le couvain non apparenté ce qui n'est pas en accord avec la théorie de la "fitness inclusive". Cette absence de discrimination est probablement due à des effets négatifs comme par exemple la diminution de la production du couvain; (4) la structure génétique d'une population de F. exsecta. Nous avons mis en évidence que la structure génétique entre des groupes de reines est significativement différente de la structure génétique entre des groupes d'ouvrières. Les données suggèrent que les reines forment des groupes basés sur une structure familiale tandis que les ouvrières sont groupées dans des unités plus grandes.