Reduction of Concrete Deterioration by Ettringite Using Crystal Growth Inhibition Techniques: Part II Field Evaluation of Inhibitor Effectiveness, TR-469, 2004

The effects of diethylenetriaminpenta(methylenephosphonic acid) (DTPMP), a phosphonate inhibitor, on the growth of delayed ettringite have been evaluated using concrete in highway US 20 near Williams, Iowa, and the cores of six highways subject to moderate (built in 1992) or minor (built in 1997) deterioration. Application of 0.01 and 0.1 vol. % DTPMP to cores was made on a weekly or monthly basis for one year under controlled laboratory-based freeze-thaw and wet-dry conditions over a temperature range of -15 degrees to 58 degrees C to mimic extremes in Iowa roadway conditions. The same concentrations of phosphonate were also applied to cores left outside (roof of Science I at Iowa State University) over the same period of time. Nineteen applications of 0.1 vol. % DTPMP with added deicing salt solution (about 23 weight % NACL) were made to US 20 during the winters of 2003 and 2004. In untreated samples, air voids, pores, and occasional cracks are lined with acicular ettringite crystals (up to 50 micrometers in length) whereas air voids, pores, and cracks in concrete from the westbound lane of US 20 are devoid of ettringite up to a depth of about 0.5 mm from the surface of the concrete. Ettringite is also absent in zones up to 6 mm from the surface of concrete slabs placed on the roof of Science I and cores subject to laboratory-based freeze-thaw experiments. In these zones, the relatively high concentration of DTPMP caused it to behave as a chelator. Stunted ettringite crystals 5 to 25 micrometers in length, occasionally coated with porlandite, form on the margins of these zones indicating that in these areas DTPMP behaved as an inhibitor due to a reduction in the concentration of phosphonate. Analyses of mixes of ettringite and DTPMP using electrospray mass spectrometry suggests that the stunting of ettringite growth is caused by the adsorption of a Ca2+ ion and a water molecule to deprotonated DTPMP on the surface of the {0001} face of ettringite. It is anticipated that by using a DTPMP concentration of between 0.001 and 0.01 vol. % for the extended life of a highway (i.e. >20 years), deterioration caused by the expansive growth of ettringite will be markedly reduced.

Tropical terrestrial model ecosystems for evaluation of soil fauna and leaf litter quality effects on litter consumption, soil microbial biomass and plant growth

The aim of this work was to evaluate whether terrestrial model ecosystems (TMEs) are a useful tool for the study of the effects of litter quality, soil invertebrates and mineral fertilizer on litter decomposition and plant growth under controlled conditions in the tropics. Forty-eight intact soil cores (17.5-cm diameter, 30-cm length) were taken out from an abandoned rubber plantation on Ferralsol soil (Latossolo Amarelo) in Central Amazonia, Brazil, and kept at 28ºC in the laboratory during four months. Leaf litter of either Hevea pauciflora (rubber tree), Flemingia macrophylla (a shrubby legume) or Brachiaria decumbens (a pasture grass) was put on top of each TME. Five specimens of either Pontoscolex corethrurus or Eisenia fetida (earthworms), Porcellionides pruinosus or Circoniscus ornatus (woodlice), and Trigoniulus corallinus (millipedes) were then added to the TMEs. Leaf litter type significantly affected litter consumption, soil microbial biomass and nitrate concentration in the leachate of all TMEs, but had no measurable effect on the shoot biomass of rice seedlings planted in top soil taken from the TMEs. Feeding rates measured with bait lamina were significantly higher in TMEs with the earthworm P. corethrurus and the woodlouse C. ornatus. TMEs are an appropriate tool to assess trophic interactions in tropical soil ecossistems under controlled laboratory conditions.

Spatio-temporal sequence of cross-regulatory events in root meristem growth.

A central question in developmental biology is how multicellular organisms coordinate cell division and differentiation to determine organ size. In Arabidopsis roots, this balance is controlled by cytokinin-induced expression of SHORT HYPOCOTYL 2 (SHY2) in the so-called transition zone of the meristem, where SHY2 negatively regulates auxin response factors (ARFs) by protein-protein interaction. The resulting down-regulation of PIN-FORMED (PIN) auxin efflux carriers is considered the key event in promoting differentiation of meristematic cells. Here we show that this regulation involves additional, intermediary factors and is spatio-temporally constrained. We found that the described cytokinin-auxin crosstalk antagonizes BREVIS RADIX (BRX) activity in the developing protophloem. BRX is an auxin-responsive target of the prototypical ARF MONOPTEROS (MP), a key promoter of vascular development, and transiently enhances PIN3 expression to promote meristem growth in young roots. At later stages, cytokinin induction of SHY2 in the vascular transition zone restricts BRX expression to down-regulate PIN3 and thus limit meristem growth. Interestingly, proper SHY2 expression requires BRX, which could reflect feedback on the auxin responsiveness of SHY2 because BRX protein can directly interact with MP, likely acting as a cofactor. Thus, cross-regulatory antagonism between BRX and SHY2 could determine ARF activity in the protophloem. Our data suggest a model in which the regulatory interactions favor BRX expression in the early proximal meristem and SHY2 prevails because of supplementary cytokinin induction in the later distal meristem. The complex equilibrium of this regulatory module might represent a universal switch in the transition toward differentiation in various developmental contexts.

Growth mechanisms and timing of emplacement of a vertically layered mafic intrusion in the feeder zone of an ocean island volcano (Fuerteventura, Canary islands)

Résumé pour le grand public L'île de Fuerteventura (Canaries) offre l'occasion rare d'observer les racines d'un volcan océanique édifié il y a 25 à 30 millions d'années et complètement érodé. On y voit de nombreux petits plutons de forme et composition variées, témoignant d'autant d'épisodes de l'activité magmatique. L'un de ces plutons, appelé PX1, présente une structure inhabituelle formée d'une alternance de bandes verticales d'épaisseur métrique à hectométrique de roches sombres de composition pyroxénilique ou gabbroïque. Les pyroxénites résultent clairement de l'accumulation de cristaux de pyroxènes et non de la simple solidification d'un magma? Se pose dès lors la question de la nature du processus qui a conduit à l'accumulation verticale de niveaux concentrés en pyroxènes. En effet, les litages pyroxénitiques classiques sont subhorizontaux, car ils résultent de l'accumulation gravitaire des cristaux séparés du magma dont ils cristalli¬sent par sédimentation. Cette étude vise à identifier et comprendre les mécanismes qui ont engendré ce Iitage minéralogique vertical et l'im¬portant volume de ces faciès cumulatifs. Nous nous sommes également intéressés aux conditions de pression et de température régnant au moment de la mise en place du pluton, ainsi qu'à sa durée de vie et à sa vitesse de refroidis¬sement. Enfin une approche géochimique nous a permis de préciser la nature de la source mantellique des magmas liés à cette activité magmatique. PX1 est en réalité un complexe filonien formé à des conditions de pression et de température de 1-2 kbar et 1050- 1100°C; sa construction a nécessité au moins 150 km3 de magma. L'alternance d'horizons gabbroïques et pyroxéniti¬ques représente des injections successives de magma sous la forme de filons verticaux, mis en place dans un contexte régional en extension. L'étude des orientations des minéraux dans ces faciès révèle que les horizons gabbroïques enregistrent l'extension régionale, alors que les pyroxénites sont générées par une compaction au sein du pluton. Ceci suggère que le régime des contraintes, qui était extensif lors de l'initiation de la mise en place de PX1, est pério¬diquement devenu compressif au sein même du pluton. Cette compression serait liée à des cycles de mise en place où la vitesse de croissance du pluton dépassait celle de l'extension régionale. La différenciation observée au sein de chaque horizon, depuis des pyroxénites riches en olivine jusqu'à des pyroxé¬nites à plagioclase interstitiel et des gabbros, ainsi que la composition géochimique des minéraux qui les constituent suggèrent que chaque filon vertical s'est mis en place à partir d'un magma de composition identique, puis a évolué indépendamment des autres en fonction du régime thermique et du régime des contraintes local. Lorsque le magma en train de cristalliser s'est trouvé en compression, le liquide résiduel a été séparé des cristaux déjà formés et extrait du système, laissant derrière lui une accumulation de cristaux dont la nature et les proportions dépendaient du stade de cristallisation atteint par le magma au moment de l'extraction. Ainsi, les niveaux de pyroxénites à olivine (premier minéral à cristalliser) ont été formés lorsque le magma correspondant était encore peu cristallisé; à l'inverse, les py¬roxénites riches en plagioclase (minéral plus tardif dans la séquence de cristallisation) et certains gabbros à caractère cumulatif résultent d'une compression tardive dans le processus de cristallisation du filon concerné. Les liquides résiduels extraits des niveaux pyroxénitiques sont rarement observés dans PX1, certaines poches et filonets de com¬position anorthositique pourraient en être les témoins. L'essentiel de ces liquides a probablement gagné des niveaux supérieurs du pluton, voire la surface du volcan. L'origine du régime compressif périodique affectant les filons en voie de cristallisation est attribuée aux injections suivantes de magma au sein du pluton, qui se sont succédées à un rythme plus rapide que la vitesse de consolidation des filons. Des datations U/Pb de haute précision sur des cristaux de zircon et de baddeleyite ainsi que40Ar/39Ar sur des cris¬taux d'amphibole révèlent une initiation de la mise en place de PX1 il y a 22.1 ± 0,7 Ma; celle-ci a duré quelque 0,48 ± 0,22 à 0,52 ± 0,29 Ma. Ce laps de temps est compatible avec celui nécessaire à la cristallisation des filons individuels, qui va de moins d'une année lors de l'initiation du magmatisme à 5 ans lors du maximum d'activité de PX1. La présence de cristaux résorbés enregistrant une cristallisation complexe suggère l'existence d'une chambre mag¬matique convective sous-jacente à PX1 et périodiquement rechargée. Les compositions isotopiques des roches étu¬diées révèlent une source mantellique profonde de type point chaud avec une contribution du manteau lithosphéri- que métasomatisé présent sous les îles Canaries. Résumé L'intrusion mafique Miocène PX1 fait partie du soubassement superficiel (0.15-0.2 GPa, 1100 °Q d'un volcan d'île océanique. La particularité de ce pluton est l'existence d'alternances d'unités de gabbros et de pyroxénites qui met¬tent en évidence un litage magmatique vertical (NNE-SSW). Les horizons gabbroiques et pyroxénitiques sont constitués d'unités de différenciation métriques qui suggèrent tine mise en place par injections périodiques de filons verticaux de magma formant un complexe filonien. Chaque filon vertical a subi une différenciation parallèle à un front de solidification sub-vertical parallèle aux bords du filon. Les pyroxénites résultent du fractionnement et de l'accumulation d'olivine ± clinopyroxene ± plagioclase à partir d'un magma basaltique faiblement alcalin et sont interprétées comme étant des imités de différenciation tronquées dont le liquide interstitiel a été extrait par compaction. L'orientation préférentielle des clinopyroxènes dans ces pyroxe- nites (obtenues par analyse EBSD et micro-tomographique) révèle une composante de cisaillement simple dans la genèse de ces roches, ce qui confirme cette interprétation. La compaction des pyroxénites est probablement causée par a mise en place de filons de magma suivants. Le liquide interstitiel expulsé est probablement par ces derniers. Les clinopyroxènes des gabbros, montrent une composante de cisaillement pure suggérant qu'ils sont affectés par une déformation syn-magmatique parallèle aux zones de cisaillement NNE-SSW observées autour de PX1 et liées au contexte tectonique Miocène d'extension régionale. Ceci suggère que les gabbros sont liés à des taux de mise en place faibles à la fin de cycles d'activité magmatique et sont peu ou pas affectés par la compaction. L'initiation et la géométrie de PX1 sont donc contrôlées par le contexte tectonique régional d'extension alors que les taux et les volumes de magma dépendent de facteurs liés à la source. Des taux d'injection élevés résultent probable¬ment en une croissance du pluton supérieure à la place crée par cette extension. Dans ce cas de figure, la propagation des nouveaux dykes et l'inaptitude du magma à circuler à travers les anciens dykes cristallisés pourrait causer une augmentation de la pression non-lithostatique sur ces derniers, exprimée par un cisaillement simple et l'expulsion du liquide interstitiel qu'ils contiennent (documenté par les zones de collecte anorthositiques). Les compositions en éléments majeurs et traces des gabbros et pyroxenites de PX1 sont globalement homogènes et dépendent de la nature cumulative des échantillons. Cependant, de petites variations des concentrations en éléments traces ainsi que les teneurs en éléments traces des bordures de clinopyroxenes suggèrent que ces derniers ont subi un processus de rééquilibrage et de cristallisation in situ. L'homogénéité des compositions chimiques des échantillons, ainsi que la présence de grains de clinopyroxene résorbés suggère que le complexe filonien PX1 s'est mis en place au dessus d'une chambre magmatique périodiquement rechargée dans laquelle la convection est efficace. Chaque filon est donc issu d'un même magma, mais a subi une différenciation par cristallisation in situ (jusqu'à 70% de fraction¬nement) indépendamment des autres. Dans ces filons cristallisés, les minéraux cumulatifs subissent un rééquilibrage partiel avec les liquide interstitiel avant que ce dernier ne soit expulsé lors de la compaction (mettant ainsi un terme à la différenciation). Ce modèle de mise en place signifie qu'un minimum de 150Km3 de magma est nécessaire à la genèse de PX1, une partie de ce volume ayant été émis par le 'Central Volcanic Complex' de Fuerteventura. Les rapports isotopiques radiogéniques mesurés révèlent la contribution de trois pôles mantelliques dans la genèse du magma formant PX1. Le mélange de ces pôles HIMU, DMM et EM1 refléterai l'interaction du point chaud Cana¬rien avec un manteau lithosphérique hétérogène métasomatisé. Les petites variations de ces rapports et des teneurs en éléments traces au sein des faciès pourrait refléter des taux de fusion partielle variable de la source, résultant en un échantillonnage variable du manteau lithosphérique métasomatisé lors de son interaction avec le point chaud. Des datations U/Pb de haute précision (TIMS) sur des cristaux de zircon et de baddeleyite extraits de gabbros de PX1 révèlent que l'initiation de la cristallisation du magma a eu lieu il y a 22.10±0.07 Ma et que l'activité magmatique a duré un minimum de 0.48 à 0.52 Ma. Des âges 40Ar/39Ar obtenus sur amphibole sont de 21.9 ± 0.6 à 21.8 ± 0.3 Ma, identiques aux âges U/Pb. La combinaison de ces méthodes de datations, suggère que le temps maximum nécessaire à PX1 pour se refroidir en dessous de la température de fermeture de l'amphibole est de 0.8Ma. Ceci signifie que la durée de vie de PX1 est de 520 000 à 800 000 ans. La coexistence de cristaux de baddeleyite et de zircon dans un gabbro est attribuée à son interaction avec un fluide riche en C02 relâché par les carbonatites encaissantes lors du métamorphisme de contact généré par la mise en place de PX1 environ 160 000 ans après le début de sa mise en place. Les durées de vie obtenue sont en accord avec le modèle de mise en place suggérant une durée de cristallisation poux chaque filon allant de 1 an à 5 ans. Abstract The Miocene PX1 gabbro-pyroxenite intrusion (Fuerteventura, Canary Islands), is interpreted as the shallow-level feeder-zone (0.15-0.2 GPa and 1100-1120°C), to an ocean island volcano. The particularity of PX1 is that it displays a NNE-SSW trending vertical magmatic banding expressed by alternating gabbro and pyroxeriite sequences. The gabbro and pyroxenite sequences consist of metre-thick differentiation units, which suggest emplacement by pe¬riodic injection of magma pulses as vertical dykes that amalgamated, similarly to a sub-volcanic sheeted dyke com¬plex. Individual dykes underwent internal differentiation following a solidification front (favoured by a significant lateral/horizontal thermal gradient) parallel to the dyke edges. Pyroxenitic layers result from the fractionation and accumulation of clinopyroxene ± olivine ± plagioclase crystals from a mildly alkaline basaltic liquid and are interpre¬ted as truncated differentiation sequences, from which residual melts were extracted by compaction. Clinopyroxene mineral orientation in pyroxenites (evidenced by EBSD and micro X-ray tomography analysis) display a marked pure shear component, supporting this interpretation. Compaction and squeezing of the crystal mush is ascribed to the incoming and inflating magma pulses. The resulting expelled interstitial liquid was likely collected and erupted along with the magma flowing through the newly injected dykes. Gabbro sequences represent crystallised coalesced magma batches, emplaced at lower rates at the end of eruptive cycles, and underwent minor melt extraction as evi¬denced by clinopyroxene orientations that record a simple shear component suggesting syn-magmatic deformation parallel to observed NNF.-SSW trending shear-zones induced by the regional tensional Miocene stress-field. The initiation and geometry of PX1 is controlled by the regional extensional tectonic regime whereas rates and vo¬lumes of magma depend on source-related factors. High injection rates are likely to induce intrusion growth rates larger than could be accommodated by the regional extension. In this case, dyke tip geometry and the inability of magma to circulate through previously emplaced and crystallised dykes could result in an increase of non-lithostatic pressure on previously emplaced mushy dyke walls; generating strong pure-shear compaction and interstitial melt expulsion within the feeder-zone as recorded by the cumulitic pyroxenite bands and anorthositic collection zones. The whole-rock major and trace-element chemistry of PX1 gabbros and pyroxenites is globally homogeneous and controlled by the cumulate nature of the samples (i.e. on the modal proportions of olivine, pyroxene, plagioclase and oxides). However, small variations of whole-rock trace-element contents as well as trace-element contents of clinopyroxene rims suggest that in-situ re-equilibration and crystallisation has occurred. Additionally, the global homogeneity and presence of complex zoning of rare resorbed clinopyroxene crystals suggest that the PX1 feeder- zone overlies a periodically replenished and efficiently mixed magma chamber. Each individual dyke of magma thus originated from a compositionally constant mildly alkaline magma and differentiated independently from the others reaching up to 70% fractionation. Following dyke arrest these are affected by interaction with the trapped interstitial liquid prior to its compaction-linked expulsion (thus stopping the differentiation process). This emplacement model implies that minimum amount of approximately 150 km3 of magma is needed to generate PX1, part of it having been erupted through the overlying Central Volcanic Complex of Fuerteventura. The radiogenic isotope ratios of PX1 samples reveal the contribution on three end-members during magma genesis. This mixing of the H1MU, EMI and DMM end-members could reflect the interaction of the deep-seated Canarian mantle plume with a heterogeneous metasomatic and sepentininsed lithospheric mantle. Additionally, the observed trace-element and isotopic variations within the same fades groups could reflect varying degrees of partial melting of the source region, thus tapping more or less large areas of the metasomatised lithospheric mantle during interac¬tion with the plume. High precision ID-TIMS U/Pb zircon and baddeleyite ages from the PX1 gabbro samples, indicate initiation of magma crystallisation at 22.10 ± 0.07 Ma. The magmatic activity lasted a minimum of 0.48 to 0.52 Ma. 40Ar/39Ar amphibole ages are of 21.9 ± 0.6 to 21.8 ± 0.3, identical within errors to the U/Pb ages. The combination of the 40Ar/39Ar and U/Pb datasets imply that the maximum amount of time PX1 took to cool below amphibole Tc is 0.8 Ma, suggesting PX1 lifetime of 520 000 to 800 000 years. On top of this, the coexistence of baddeleyite and zircon in a single sample is ascribed to the interaction of PX1 with C02-rich carbonatite-derived fluids released from the host-rock carbonatites during contact metamorphism 160 000 years after PX1 initiation. These ages are in agreement with the emplacement model, implying a crystallisation time of less than 1 to 5 years for individual dykes.

Water, energy and early postnatal growth in preterm infants.

Non-invasive methods, including stable isotope techniques, indirect calorimetry, nutritional balance and skinfold thickness, have given a new insight into early postnatal growth in neonates. Neonates and premature infants in particular, create an unusual opportunity to study the fluid and metabolic adaptation to extrauterine life because their physical environment can be controlled, fluid and energy balance can be measured and the link between metabolism and the energetics of their postnatal growth can be assessed accurately. Thus the postnatal time course of total body water, heat production, energy cost of growth and composition of weight gain have been quantified in a series of "healthy" low-birth-weight premature infants. These results show that total body water is remarkably stable between postnatal days 3-21. Energy expenditure and heat production rates increase postnatally from mean values of 40 kcal/kg/day during the first week to 60 kcal/kg/day in the third week. An apparent energy balance deficit of 180 kcal/kg can be ascribed to premature delivery. The cost of protein metabolism is the highest energy demanding process related to growth. The fact that nitrogen balance becomes positive within 72 h after birth places the newborn in a transitional situation of dissociated balance between energy and protein metabolism during early postnatal growth: skinfold thickness, dry body mass and fat decrease, while there is a gain in protein and increase in supine length. This particular situation ends during the second postnatal week and soon thereafter the rate of weight gain matches statural growth. The goals of the following review are to summarize data on total body water and energy metabolism in premature infants and to discuss how they correlate with physiological aspects of early postnatal growth.

Comprehensive Study of Crystal Growth from Solution

Crystal growth is an essential phase in crystallization kinetics. The rate of crystal growth provides significant information for the design and control of crystallization processes; nevertheless, obtaining accurate growth rate data is still challenging due to a number of factors that prevail in crystal growth. In industrial crystallization, crystals are generally grown from multi-componentand multi-particle solutions under complicated hydrodynamic conditions; thus, it is crucial to increase the general understanding of the growth kinetics in these systems. The aim of this work is to develop a model of the crystal growth rate from solution. An extensive literature review of crystal growth focuses on themodelling of growth kinetics and thermodynamics, and new measuring techniques that have been introduced in the field of crystallization. The growth of a singlecrystal is investigated in binary and ternary systems. The binary system consists of potassium dihydrogen phosphate (KDP, crystallizing solute) and water (solvent), and the ternary system includes KDP, water and an organic admixture. The studied admixtures, urea, ethanol and 1-propanol, are employed at relatively highconcentrations (of up to 5.0 molal). The influence of the admixtures on the solution thermodynamics is studied using the Pitzer activity coefficient model. Theprediction method of the ternary solubility in the studied systems is introduced and verified. The growth rate of the KDP (101) face in the studied systems aremeasured in the growth cell as a function of supersaturation, the admixture concentration, the solution velocity over a crystal and temperature. In addition, the surface morphology of the KDP (101) face is studied using ex situ atomic force microscopy (AFM). The crystal growth rate in the ternary systems is modelled on the basis of the two-step growth model that contains the Maxwell-Stefan (MS) equations and a surface-reaction model. This model is used together with measuredcrystal growth rate data to develop a new method for the evaluation of the model parameters. The validation of the model is justified with experiments. The crystal growth rate in an imperfectly mixed suspension crystallizer is investigatedusing computational fluid dynamics (CFD). A solid-liquid suspension flow that includes multi-sized particles is described by the multi-fluid model as well as by a standard k-epsilon turbulence model and an interface momentum transfer model. The local crystal growth rate is determined from calculated flow information in a diffusion-controlled crystal growth regime. The calculated results are evaluated experimentally.

Patterns of primary growth increments in otoliths of Sparus aurata larvae in relation to water temperature and food consumption

Sparus aurata larvae reared under controlled water-temperature conditions during the first 24 days after hatching displayed a linear relationship between age (t) and standard length (SL): SL = 2.68 + 0.19 t (r2 = 0.91l). Increments were laid down in the sagittae with daily periodicity starting on day of hatching. Standard length (SL) and sagittae radius (OR) were correlated: SL(mm) = 2.65 + 0.012 OR(mm). The series of measurements of daily growth increment widths (DWI), food density and water temperature were analyzed by means of time series analysis. The DWI series were strongly autocorrelated, the growth on any one day was dependent upon growth on the previous day. Time series of water temperatures showed, as expected, a random pattern of variation, while food consumed daily was a function of food consumed the two previous days. The DWI series and the food density were correlated positively at lags 1 and 2. The results provided evidence of the importance of food intake upon the sagittae growth when temperature is optimal (20ºC). Sagittae growth was correlated with growth on the previous day, so this should be taken into account when fish growth is derived from sagittae growth rates.

A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

Postoperative Adjuvant Lapatinib and Concurrent Chemoradiotherapy Followed by Maintenance Lapatinib Monotherapy in High-Risk Patients With Resected Squamous Cell Carcinoma of the Head and Neck: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study.

PURPOSE: This multicenter phase III study evaluated the efficacy and safety of lapatinib, an epidermal growth factor receptor/ErbB2 inhibitor, administered concomitantly with chemoradiotherapy and as maintenance monotherapy in patients with high-risk surgically treated squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with resected stage II to IVA SCCHN, with a surgical margin ≤ 5 mm and/or extracapsular extension, were randomly assigned to chemoradiotherapy (66 Gy total radiation dose and cisplatin 100 mg/m(2) per day administered on days 1, 22, and 43) plus placebo or lapatinib (1,500 mg per day) before and during chemoradiotherapy, followed by 12 months of maintenance monotherapy. RESULTS: Six hundred eighty-eight patients were enrolled (lapatinib, n = 346; placebo, n = 342). With a median follow-up time of 35.3 months, the study ended early because of the apparent plateauing of disease-free survival (DFS) events. Median DFS assessed by an independent review committee was 53.6 months and not reached for lapatinib and placebo, respectively (hazard ratio, 1.10; 95% CI, 0.85 to 1.43). Investigator-assessed results confirmed the independent review committee assessment. No significant differences in DFS by human papillomavirus status or overall survival were observed between treatment arms. Similar numbers of patients in both treatment arms experienced adverse events (AEs), with more patients in the lapatinib arm than the placebo arm experiencing serious AEs (48% v 40%, respectively). The most commonly observed treatment-related AEs were diarrhea and rash, both predominantly in the lapatinib arm. CONCLUSION: Addition of lapatinib to chemoradiotherapy and its use as long-term maintenance therapy does not offer any efficacy benefits and had additional toxicity compared with placebo in patients with surgically treated high-risk SCCHN.

Early nutritional determinants in cardio-metabolic programming – A prospective randomized controlled dietary intervention study

Western societies have been faced with the fact that overweight, impaired glucose regulation and elevated blood pressure are already prevalent in pediatric populations. This will inevitably mean an increase in later manifestations of cardio-metabolic diseases. The dilemma has been suggested to stem from fetal life and it is surmised that the early nutritional environment plays an important role in the process called programming. The aim of the present study was to characterize early nutritional determinants associating with cardio-metabolic risk factors in fetuses, infants and children. Further, the study was designated to establish whether dietary counseling initiated in early pregnancy can modify this cascade. Healthy mother-child pairs (n=256) participating in a dietary intervention study were followed from early pregnancy to childhood. The intervention included detailed dietary counseling by a nutritionist targeting saturated fat intake in excess of recommendations and fiber consumption below recommendations. Cardio-metabolic programming was studied by characterizing the offspring’s cardio-metabolic risk factors such as over-activation of the autonomic nervous system, elevated blood pressure and adverse metabolic status (e.g. serum high split proinsulin concentration). Fetal cardiac sympathovagal activation was measured during labor. Postnatally, children’s blood pressure was measured at six-month and four-year follow-up visits. Further, infants’ metabolic status was assessed by means of growth and serum biomarkers (32-33 split proinsulin, leptin and adiponectin) at the age of six months. This study proved that fetal cardiac sympathovagal activity was positively associated with maternal pre-pregnancy body mass index indicating adverse cardio-metabolic programming in the offspring. Further, a reduced risk of high split proinsulin in infancy and lower blood pressure in childhood were found in those offspring whose mothers’ weight gain and amount and type of fats in the diet during pregnancy were as recommended. Of note, maternal dietary counseling from early pregnancy onwards could ameliorate the offspring’s metabolic status by reducing the risk of high split proinsulin concentration, although it had no effect on the other cardio-metabolic markers in the offspring. At postnatal period breastfeeding proved to entail benefits in cardio-metabolic programming. Finally, the recommended dietary protein and total fat content in the child’s diet were important nutritional determinants reducing blood pressure at the age of four years. The intrauterine and immediate postnatal period comprise a window of opportunity for interventions aiming to reduce the risk of cardio-metabolic disorders and brings the prospect of achieving health benefits over one generation.

Carbohydrate intake in children - associations with dietary intakes, growth, serum lipids,and dental health. The STRIP Project

This study is part of the STRIP study, which is a long-term, randomized controlled trial, designed to decrease the exposure of children in the intervention group (n=540) to known risk factors of atherosclerosis. The main focus of the intervention was the quality of dietary fat. The control group (n=522) did not receive any individualized counselling. Food consumption was evaluated with food records, and blood samples were drawn and growth was measured regularly for all participating children from 13 months to 9 years. A subsample of 66 children participated in a dental health survey. The number of studies on children’s carbohydrate intake, especially fibre intake, is insufficient. The current international recommendations for fibre intake in children are based on average assumptions and data extrapolated from intakes in adults and intake recommendations for adults. Finnish nutrition recommendations lack strict recommendations for dietary fibre in children. Due to fibre’s high bulk volume, excessive dietary fibre is considered to decrease energy density and hence it may have an adverse effect on growth. If fats are reduced from the diet, the low-fat diet may become high in sucrose. Therefore, especially in the STRIP study, it is important to determine the use of fibre and sucrose in children and possible associations with growth and nutrition as well as dental health. The results of the present study indicate that a high fibre intake does not displace energy or disturb growth in children and that children with high fibre intake have better quality of diet than those with low fibre intake. Additionally, dietary fibre intake associated inversely with serum cholesterol concentration. Other carbohydrates also affected serum lipid levels as well, since total carbohydrates, sucrose, and fructose increased serum triglyceride concentration. Total carbohydrate intake reduced HDL cholesterol concentration only in children with apoE3 or apoE4 phenotype. Over the period from the 1970s to the 1990s the dental health of children in Finland has substantially improved despite an increase in sucrose intake. The improvement was thought to be due to improved dental hygiene and the use of fluorine. However, during the past twenty years improvement in dental health has stopped. The present study showed that high long-term sugar intake increases risk of caries in children. High intake of sugar had also negative effects on the diet of children, because it worsens dietary quality by displacing essential nutrients. Furthermore, the quality of dietary fat was worse in children with high sucrose intake. In this study the children’s high sucrose intake was not associated with overweight, but interestingly, it associated inversely with growth.

Rice seedling and plant development as affected by increasing rates of penoxsulam under controlled environments

Rice is a major staple in many countries. Weed control is one of the factors limiting higher rice yield. ALS (acetolactate synthase)-inhibiting herbicides are desirable weed control herbicides because of their high efficacy, low toxicity to mammalians, and low rates used. An important herbicide characteristic is high selectivity to the crop, since it facilitates fast crop establishment and greater crop advantage over the weeds. The objectives of this work were to study the effects of increasing rates of the ALS-inhibiting herbicide penoxsulam on seed integrity and germination, and seedling and plant development of rice cv. BRS Pelota under controlled laboratory and greenhouse conditions. The results showed that penoxsulam affected rice germination and seedling and plant growth at rates above 54 g a.i. ha-1, and that penoxsulam is safe for rice seedling development at the currently recommended rates.

Use of growth retardants in wheat

In general, lodging has been controlled by restricting nitrogen fertilizer application and/or using short cultivars. Growth retardants can also be used to solve this problem.The objective of this study was to evaluate the effect of rates and application times of three growth retardants on Pioneiro wheat cultivar. The trial was carried out in Viçosa-MG, from May to September 2005, in a factorial and hierarchical scheme, in a randomized block design with four replications and a control treatment. The treatments consisted of 500, 1,000 and 1,500 g ha-1 of chlormequat; 62.5, 125 and 187.5 g ha-1 of trinexapac-ethyl and 40, 80 and 120 g ha-1 of paclobutrazol applied at growth stages 6 or 8, growth stage used on the scale of Feeks and Large, and a control treatment without growth retardant application. Only trinexapac-ethyl and chlormequat were efficient in reducing plant height; the effect of chlormequat and paclobutrazol on plant height was independent of the application time, but the trinexapac-ethyl at growth stage 8 produced shorter plant height than at stage 6. Increasing growth retardant rates produced shorter plant heights; chlormequat and paclobutrazol did not affect grain yield. However, the highest trinexapac-ethyl rates reduced wheat yield.