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.

Epidermal growth factor (EGF) stimulation of cultured brain cells. II. Increased production of extracellular soluble proteins.

The production of extracellular soluble proteins was studied in serum-free aggregating cell cultures of fetal rat telencephalon labeled on culture day 7 with a mixture of radioactive amino acid precursors. Cultures treated continuously with epidermal growth factor (EGF; 20 ng/ml) showed a generally increased protein secretion and a particularly enhanced production of a few distinct extracellular proteins. The time lag of this response after an initial dose of EGF (25 ng/ml) on day 7 was 48 h. The total macromolecular radioactivity that accumulated within 96 h of labeling in the media of EGF-treated cultures was 175% of untreated controls, whereas no difference was found in the proportions of intracellular amino acid incorporation. Cultures which received a single dose of EGF (25 ng/ml) on day 1 showed still a greatly increased protein secretion on day 7. Prevention of extracellular protein accumulation by reducing the initial cell number and increasing the rate of media changes did not affect the EGF-induced stimulation of the two glial enzymes, glutamine synthetase and 2',3'-cyclic nucleotide 3'-phosphohydrolase. The results suggest that both the increased production of extracellular proteins and the enhanced development of glial enzymatic activities reflect the stimulated phenotypic expression of EGF-sensitive brain cells.

Earthquake impacts in old-growth Nothofagus forests in New Zealand

Six stands located on different land forms in mixed old-growth Nothofagus forests in the Matiri Valley (northwest of South Island. New Zealand) were sampled to examine the effects of two recent large earthquakes on tree establishment and tree-ring growth, and how these varied across land forms. 50 trees were cor ed in each stand to determine age structure and the cores were cross-dated to precisely date unusual periods of radial growth. The 1968 earthquake (M = 7.1, epicentre 35 km from the study area) had no discernible impact on the sampled stands. The impact of the 1929 earthquake (M = 7.7, epicentre 20 kin from the study area) varied between stands, depending on whether or not they had been damaged by soil or rock movement. In all stands, the age structures showed a pulse of N. fusca establishment following the 1929 earthquake, with this species dominating establishment in large gaps created by landslides. Smaller gaps, created by branch or tree death, were closed by both N. fusca and N. menziesii. The long period of releases (1929-1945) indicates that direct earthquake damage was not the only cause of tree death, and that many trees died subsequently most likely of pathogen attack or a drought in the early 1930s. The impacts of the 1929 earthquake are compared to a storm in 1905 and a drought in 1974-1978 which also affected forests in the region. Our results confirm that earthquakes are an important factor driving forest dynamics in this tectonically active region, and that the diversity of earthquake impacts is a major source of heterogeneity in forest structure and regeneration.

Enhanced visuospatial memory following intracerebroventricular administration of nerve growth factor

The present work assessed the effects of intracerebroventricular injections of rh recombined human nerve growth factor (rh NGF) (5 micrograms/2.5 microl) at postnatal days 12 and 13 upon the development of spatial learning capacities. The treated rats were trained at the age of 22 days to escape onto an invisible platform at a fixed position in space in a Morris navigation task. For half of the subjects, the training position was also cued, a procedure aimed at facilitating escape and at reducing attention to the distant spatial cues. Later, at the age of 6 months, all the rats were trained in a radial-arm maze task. Treatment effects were found in both immature and adult rats. The injection of NGF improved the performance in the Morris navigation task in both training conditions. There was a significant reduction in the escape latency and an increased bias toward the training platform quadrant during probe trials. The most consistent effect was the precocious development of an adult-like spatial memory. In the radial-arm maze, the NGF-treated rats made significantly fewer reentries than vehicle rats and this effect was particularly marked in the treated female rats. Taken together, these experiments reveal that the development and the maintenance of an accurate spatial representation are tightly related to the development of brain structures facilitated by the action of NGF. Moreover, these experiments demonstrate that an acute pharmacological treatment that leads to a transient modification in the choline acetyltransferase activity can induce a behavioral change long after the treatment.

NF-kappaB transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth.

A novel function of NF-kappaB in the development of most ectodermal appendages, including two types of murine pelage hair follicles, was detected in a mouse model with suppressed NF-kappaB activity (c(IkappaBalphaDeltaN)). However, the developmental processes regulated by NF-kappaB in hair follicles has remained unknown. Furthermore, the similarity between the phenotypes of c(IkappaBADeltaN) mice and mice deficient in Eda A1 (tabby) or its receptor EdaR (downless) raised the issue of whether in vivo NF-kappaB regulates or is regulated by these novel TNF family members. We now demonstrate that epidermal NF-kappaB activity is first observed in placodes of primary guard hair follicles at day E14.5, and that in vivo NF-kappaB signalling is activated downstream of Eda A1 and EdaR. Importantly, ectopic signals which activate NF-kappaB can also stimulate guard hair placode formation, suggesting a crucial role for NF-kappaB in placode development. In downless and c(IkappaBalphaDeltaN) mice, placodes start to develop, but rapidly abort in the absence of EdaR/NF-kappaB signalling. We show that NF-kappaB activation is essential for induction of Shh and cyclin D1 expression and subsequent placode down growth. However, cyclin D1 induction appears to be indirectly regulated by NF-kappaB, probably via Shh and Wnt. The strongly decreased number of hair follicles observed in c(IkappaBalphaDeltaN) mice compared with tabby mice, indicates that additional signals, such as TROY, must regulate NF-kappaB activity in specific hair follicle subtypes.

Role of beta-1 integrin in tumor growth and dissemination

SUMMARY Cancer is one of the leading causes of disease-related mortality. In most cases, death is due to the spread of cells from the primary tumor to distant sites causing formation of metastases. To become tumorigenic, cells should acquire ability, including self-sufficiency in growth signals, insensitivity to anti-growth signals, resistance to apoptosis, sustained angiogenesis, limitless replicative potential and tissue invasion and metastasis. Tumor progression depends, in part on the relationship between tumor cells and host tissue stroma, characterized by changes of tumor cell adhesion to their microenvironment and activation of a variety of extracellular proteases that play a role in ECM degradation. integrins are adhesion proteins implicated in tumorigenesis. Their main function is to mediate cell adhesion to the ECM or to other cells and to create a link between the ECM and the cytoskeleton. Tumor cells like normal cells use integrins to attach to ECM, migrate into surrounding tissues and derive survival and growth signals. Integrin-dependent adhesion and migration are thought to play an important role in tumor dissemination. A strategy was designed to address the role of β1 integrin tumor growth and dissemination. Murine mammary carcinoma (TA3) cells were stably transfected with a soluble β1 integrin construct, which is anticipated to play a dominant negative role, being able to associate with different α-subunits expressed on the cell surface but unable to transduce signals to the nucleus. Results from studies based on soluble β1 integrin TA3 transfectants showed that 1) the integrin expression pattern at the cell surface changed with an induction of α2β1 and α5β1 heterodimers; 2) adhesion to collagens, especially collagen I was increased; 3) tumor dissemination after intrape-ritoneal injection in syngeneic mice was abolished and 4) local growth after orthotopic injection was maintained but delayed. Taken together, the data presented here suggest that β1 integrin plays a potentially important role in the regulation of tumor behavior. RESUME Le cancer est une des principales causes de mortalité suite à une maladie. Dans la plupart des cas, la mort est la conséquence de la dissémination de cellules, provenant de la tumeur primaire, dans des endroits distants et causant la formation de métastases. Afin de devenir cancéreuse, une cellule doit acquérir certaines capacités, telles qu'une auto-suffisance en facteurs de croissance, une insensibilité aux facteurs empêchant la croissance cellulaire, une résistance à l'apoptose, une angiogénèse soutenue, un potentiel de réplication illimité et une capacité à pénétrer dans les tissus et à former des colonies métastatiques. La progression d'une tumeur dépend, en partie, de la relation entre les cellules tumorales et les cellules tissulaires de l'hôte. Cette relation est caractérisée par des modifications des cellules tumorales quant à leur adhésion au microenvironnement et à l'activation de protéases qui permettent de dégrader la matrice extracellulaire. Les intégrines sont des protéines impliquées dans le développement tumoral. Leur fonction principale est de réguler l'adhésion des cellules à la matrice extracellulaire, ou à d'autres cellules, et de créer un lien entre cette matrice extracellulaire et le cytosquelette. Les cellules tumorales utilisent également les intégrines pour se lier à la matrice extracellulaire, pour migrer dans les tissus adjacents et pour induire des signaux de croissance et de survie. Ces événements d'adhésion et de migration, qui dépendent des intégrines, jouent un rôle primordial dans la dissémination des cellules cancéreuses. Une stratégie a été élaborée afin de définir le rôle de l'intégrine β1 durant la croissance et la dissémination des cellules tumorales. Des cellules provenant d'un carcinome de la glande mammaire (TA3) ont été transfectées de manière stable avec un vecteur contenant la séquence codante de la partie extracellulaire de l'intégrine β1. L'intégrine tronquée doit être capable de se lier aux sous-unités α exprimées à la surface de la cellule, mais doit être incapable de transmettre un signal à l'intérieur de la cellule. Les résultats obtenus avec les cellules TA3 transfectées contenant l'intégrine β1 soluble montrent que I) le répertoire d'expression des intégrines à la surface de la cellule a changé en faveur des hétérodimères α2β1 et α5β1; 2) l'adhésion aux collagènes, particulièrement au collagène de type I a augmenté; 3) la dissémination des cellules tumorales après une injection intrapéritonéale est empêchée; 4) la croissance tumorale après une injection orthotopique est conservée mais retardée. Ces résultats montrent que l'intégrine β1 joue un rôle primordial dans la régulation du comportement tumoral.

Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets.

Fibroblast growth factor 23 (FGF23) is a circulating factor secreted by osteocytes that is essential for phosphate homeostasis. In kidney proximal tubular cells FGF23 inhibits phosphate reabsorption and leads to decreased synthesis and enhanced catabolism of 1,25-dihydroxyvitamin D3 (1,25[OH]2 D3 ). Excess levels of FGF23 cause renal phosphate wasting and suppression of circulating 1,25(OH)2 D3 levels and are associated with several hereditary hypophosphatemic disorders with skeletal abnormalities, including X-linked hypophosphatemic rickets (XLH) and autosomal recessive hypophosphatemic rickets (ARHR). Currently, therapeutic approaches to these diseases are limited to treatment with activated vitamin D analogues and phosphate supplementation, often merely resulting in partial correction of the skeletal aberrations. In this study, we evaluate the use of FGFR inhibitors for the treatment of FGF23-mediated hypophosphatemic disorders using NVP-BGJ398, a novel selective, pan-specific FGFR inhibitor currently in Phase I clinical trials for cancer therapy. In two different hypophosphatemic mouse models, Hyp and Dmp1-null mice, resembling the human diseases XLH and ARHR, we find that pharmacological inhibition of FGFRs efficiently abrogates aberrant FGF23 signaling and normalizes the hypophosphatemic and hypocalcemic conditions of these mice. Correspondingly, long-term FGFR inhibition in Hyp mice leads to enhanced bone growth, increased mineralization, and reorganization of the disturbed growth plate structure. We therefore propose NVP-BGJ398 treatment as a novel approach for the therapy of FGF23-mediated hypophosphatemic diseases.

The effects of arterial flow on platelet activation, thrombus growth, and stabilization.

Injury of an arterial vessel wall acutely triggers a multifaceted process of thrombus formation, which is dictated by the high-shear flow conditions in the artery. In this overview, we describe how the classical concept of arterial thrombus formation and vascular occlusion, driven by platelet activation and fibrin formation, can be extended and fine-tuned. This has become possible because of recent insight into the mechanisms of: (i) platelet-vessel wall and platelet-platelet communication, (ii) autocrine platelet activation, and (iii) platelet-coagulation interactions, in relation to blood flow dynamics. We list over 40 studies with genetically modified mice showing a role of platelet and plasma proteins in the control of thrombus stability after vascular injury. These include multiple platelet adhesive receptors and other junctional molecules, components of the ADP receptor signalling cascade to integrin activation, proteins controlling platelet shape, and autocrine activation processes, as well as multiple plasma proteins binding to platelets and proteins of the intrinsic coagulation cascade. Regulatory roles herein of the endothelium and other blood cells are recapitulated as well. Patient studies support the contribution of platelet- and coagulation activation in the regulation of thrombus stability. Analysis of the factors determining flow-dependent thrombus stabilization and embolus formation in mice will help to understand the regulation of this process in human arterial disease.

The Pseudomonas aeruginosa toxin L-2-amino-4-methoxy-trans-3-butenoic acid inhibits growth and induces encystment in Acanthamoeba castellanii.

L-2-Amino-4-methoxy-trans-3-butenoic acid (AMB) is a toxic antimetabolite produced by the opportunistic pathogen Pseudomonas aeruginosa. To evaluate its importance as a potential virulence factor, we tested the host response towards AMB using an Acanthamoeba castellanii cell model. We found that AMB (at concentrations ≥ 0.5 mM) caused amoebal encystment in salt buffer, while inhibiting amoebal growth in rich medium in a dose-dependent manner. However, no difference in amoebal plaque formation was observed on bacterial lawns of wild type and AMB-negative P. aeruginosa strains. We thereby conclude that AMB may eventually act as a virulence factor, but only at relatively high concentrations.

Controlled nerve growth factor release from multi-ply alginate/chitosan-based nerve conduits.

The delivery kinetics of growth factors has been suggested to play an important role in the regeneration of peripheral nerves following axotomy. In this context, we designed a nerve conduit (NC) with adjustable release kinetics of nerve growth factor (NGF). A multi-ply system was designed where NC consisting of a polyelectrolyte alginate/chitosan complex was coated with layers of poly(lactide-co-glycolide) (PLGA) to control the release of embedded NGF. Prior to assessing the in vitro NGF release from NC, various release test media, with and without stabilizers for NGF, were evaluated to ensure adequate quantification of NGF by ELISA. Citrate (pH 5.0) and acetate (pH 5.5) buffered saline solutions containing 0.05% Tween 20 yielded the most reliable results for ELISA active NGF. The in vitro release experiments revealed that the best results in terms of reproducibility and release control were achieved when the NGF was embedded between two PLGA layers and the ends of the NC tightly sealed by the PLGA coatings. The release kinetics could be efficiently adjusted by accommodating NGF at different radial locations within the NC. A sustained release of bioactive NGF in the low nanogram per day range was obtained for at least 15days. In conclusion, the developed multi-ply NGF loaded NC is considered a suitable candidate for future implantation studies to gain insight into the relationship between local growth factor availability and nerve regeneration.

Phenotypic variability of retinocytomas: preregression and postregression growth patterns.

AIM: To describe the incidence of retinocytomas, their variability at presentation and their growth patterns both before and after regression.¦METHODS: Medical notes of the 525 patients of the Jules-Gonin Eye Hospital Retinoblastoma Clinic between 1964 and 2008 were reviewed and the charts of 36 patients with retinocytomas and/or phthisis bulbi were selected.¦RESULTS: The proportion of patients with retinocytomas and/or phthisis bulbi was 3.2%. The mean age at diagnosis was 28.7±17 years. Five tumours presented a cystic pattern (5.8%). Evidence of aggressive exophytic disease prior to spontaneous regression was documented in two eyes, and of invasive endophytic disease (regressed vitreous seeding or internal limiting membrane disruption) in three eyes. Twenty patients were followed with a mean follow-up of 44±60 months. Tumour growth was observed in 16% cases, benign cystic enlargement in 4% and malignant transformation in 12%.¦CONCLUSION: This large study of retinocytomas substantially expands the published features of retinocytoma by describing the cystic nature of some retinocytomas as well as clinical characteristics of the endophytic and exophytic preregression growth patterns. The authors report two different patterns of reactivation: benign cystic enlargement and malignant transformation with or without cystic growth. Higher than previously reported frequency of growth and possible life-threatening complications impose close lifetime follow-up of retinocytoma patients.

Deposits of transforming growth factor-beta-induced protein in granular corneal dystrophy type II after LASIK.

PURPOSE: To analyze components of the deposits in the corneal flap interface of granular corneal dystrophy type II (GCD II) patients after laser in situ keratomileusis (LASIK). METHODS: Four corneal GCD II specimens displaying disease exacerbation after LASIK were analyzed. Three of these specimens included the recipient corneal button after penetrating keratoplasty or deep lamellar keratoplasty for advanced GCD II after LASIK. The fourth specimen, a similar case of GCD II after LASIK, included the amputated corneal flap. Specimens were processed for histopathologic and immunohistochemical analyses. RESULTS: Corneal stromal deposits in the LASIK flaps of all specimens were stained with 3 anti-transforming growth factor-beta-induced protein (TGFBIp) antibodies. The deposits displayed bright red color staining with Masson trichrome; however, negative staining was seen with Congo red, suggesting that hyaline is the main component localizing to the TGFBIp deposits rather than amyloid. CONCLUSIONS: Amorphous granular material deposited along the interface of the LASIK flap in GCD II corneas is composed mainly of hyaline deposits.

Analysis of secondary growth in the Arabidopsis shoot reveals a positive role of jasmonate signalling in cambium formation.

After primary growth, most dicotyledonous plants undergo secondary growth. Secondary growth involves an increase in the diameter of shoots and roots through formation of secondary vascular tissue. A hallmark of secondary growth initiation in shoots of dicotyledonous plants is the initiation of meristematic activity between primary vascular bundles, i.e. in the interfascicular regions. This results in establishment of a cylindrical meristem, namely the vascular cambium. Surprisingly, despite its major implications for plant growth and the accumulation of biomass, the molecular regulation of secondary growth is only poorly understood. Here, we combine histological, molecular and genetic approaches to characterize interfascicular cambium initiation in the Arabidopsis thaliana inflorescence shoot. Using genome-wide transcriptional profiling, we show that stress-related and touch-inducible genes are up-regulated in stem regions where secondary growth takes place. Furthermore, we show that the products of COI1, MYC2, JAZ7 and the touch-inducible gene JAZ10, which are components of the JA signalling pathway, are cambium regulators. The positive effect of JA application on cambium activity confirmed a stimulatory role of JA in secondary growth, and suggests that JA signalling triggers cell divisions in this particular context.

Alterations of bone microarchitecture in young patients with inflammatory bowel diseases are associated with fracture risk during growth

Aims: Inflammatory bowel diseases (IBD) appearing during childhood and adolescence compromise peak bone mass acquisition and increase fracture risk. The structural determinants of bone fragility in IBD however remain unknown. Methods: We investigated volumetric bone mineral density (vBMD), trabecular and cortical bone microstructure at distal radius and tibia by high-resolution pQCT (XtremeCT, Scanco, Switzerland), aBMD at distal radius, hip and spine and vertebral fracture assessment (VFA) by DXA in 107 young patients (mean age 22.8 yrs, range 12.2-33.7 yrs; 62 females and 45 males) with Crohn's disease (n=75), ulcerative colitis (n=25), undetermined colitis (n=2), and no definitive diagnosis (n=5), and in 389 healthy young individuals. Results: Mean disease duration was 6.1 yrs, 89/107 IBD patients received corticosteroids, 83 other immunomodulators, and 59 vitamin D. Clinical fractures were reported by 38 patients (mean age at 1st fracture, 12.6 yrs), the vast majority of the forearm, arm or hand; 5 had vertebral crush fractures (Grade 1 or 2) and 11 had multiple fractures. As compared to healthy controls (matched 2:1 for age, sex, height and fracture history), the 102 patients with established IBD had similar weight but significantly lower aBMD at all sites, lower trabecular (Tb) BV/TV and number, and greater Tb separation and inhomogeneous Tb distribution (1/SD TbN) at both distal radius and tibia, lower tibia cortical thickness (CTh), but no differences in cortical vBMD nor bone perimeter. Among IBD's, aBMD was not associated with fractures (by logistic regression adjusted for age, age square, sex, height, weight and protein intake). However, radius and tibia Tb BV/TV, thickness and SD 1/TbN, as well as radius Tb separation and perimeter, were significantly associated with fracture risk (fully adjusted as above), whereas cortical vBMD and CTh were not. After adjustment for aBMD at radius, respectively at femur neck, radius SD 1/TbN and tibia BV/TV, TbTh and perimeter remained independently associated with fracture risk. Conclusions: Young subjects with IBD have low bone mass and poor bone microarchitecture compared to healthy controls. Alterations of bone microarchitecture, particularly in the trabecular bone compartment, are specifically associated with increased fracture risk during growth.

Growth arrest-specific gene 6 » (Gas6) as an intra-hospital mortality predictor for patients in septic shock

Aim: Gas6 is known to be elevated in sepsis, correlating with the severity of infection and¦organ failure. We aimed to investigate the performance of Gas6 plasma levels at¦admission to predict the risk of mortality in a cohort of septic patients.¦Methods: We used prospectively collected data and plasma samples from the "Sepsis¦Cohorte Romande". Gas6 level was measured by ELISA at admission and expressed in¦percentage relative to its level in a pool of normal plasma.¦Results: Non-survivors (n=21) presented higher Gas6 levels than survivors (n=73) (median¦258% vs 164%, IQR 194 and 117 respectively) (p=0.0027). Gas6 correlated positively with¦different cytokines and was the best mortality predictor, as shown by the ROC curves area.¦In patients with septic shock (n=66), using 249% as a cut-off value, Gas6 measurement¦had a specificity of 67% and a sensitivity of 81% for predicting mortality. ROC curve area¦was 0.75. Positive and negative predictive values were 57% and 87%, respectively.¦Conclusion: Thus, Gas6 plasma level at admission might be a useful tool to predict¦mortality in patients with septic shock. Although Gas6 hold promise as an early sepsis¦marker, its precise implication in sepsis remains to be elucidated. Our observation should¦be further investigated in larger prospective clinical trials.