The Receptor Tyrosine Kinase Alk Controls Neurofibromin Functions in Drosophila Growth and Learning

Anaplastic Lymphoma Kinase (Alk) is a Receptor Tyrosine Kinase (RTK) activated in several cancers, but with largely unknown physiological functions. We report two unexpected roles for the Drosophila ortholog dAlk, in body size determination and associative learning. Remarkably, reducing neuronal dAlk activity increased body size and enhanced associative learning, suggesting that its activation is inhibitory in both processes. Consistently, dAlk activation reduced body size and caused learning deficits resembling phenotypes of null mutations in dNf1, the Ras GTPase Activating Protein-encoding conserved ortholog of the Neurofibromatosis type 1 (NF1) disease gene. We show that dAlk and dNf1 co-localize extensively and interact functionally in the nervous system. Importantly, genetic or pharmacological inhibition of dAlk rescued the reduced body size, adult learning deficits, and Extracellular-Regulated-Kinase (ERK) overactivation dNf1 mutant phenotypes. These results identify dAlk as an upstream activator of dNf1-regulated Ras signaling responsible for several dNf1 defects, and they implicate human Alk as a potential therapeutic target in NF1

Effect of Ultrasonic-Assisted Blanching on Size Variation, Heat Transfer, and Quality Parameters of Mushrooms

The main aim of this work was to assess the influence of the application of power ultrasound during blanching of mushrooms (60 90 °C) on the shrinkage, heat transfer, and quality parameters. Kinetics of mushroom shrinkage was modeled and coupled to a heat transfer model for conventional (CB) and ultrasonic-assisted blanching (UB). Cooking value and the integrated residual enzymatic activity were obtained through predicted temperatures and related to the hardness and color variations of mushrooms, respectively. The application of ultrasound led to an increase of shrinkage and heat transfer rates, being this increase more intense at low process temperatures. Consequently, processing time was decreased (30.7 46.0 %) and a reduction in hardness (25.2 40.8 %) and lightness (13.8 16.8 %) losses were obtained. The best retention of hardness was obtained by the UB at 60 °C, while to maintain the lightness it was the CB and UB at 90 °C. For enhancing both quality parameters simultaneously, a combined treatment (CT), which consisted of a CB 0.5 min at 90 °C and then an UB 19.9min at 60 °C, was designed. In this manner, compared with the conventional treatment at 60 °C, reductions of 39.1, 27.2, and 65.5 % for the process time, hardness and lightness losses were achieved, respectively. These results suggest that the CT could be considered as an interesting alternative to CB in order to reduce the processing time and improve the overall quality of blanched mushrooms.The authors acknowledge the financial support of Consejo Nacional de Investigaciones Cientificas y Tecnicas and Universidad Nacional de La Plata from Argentina, Erasmus Mundus Action 2-Strand 1 and EuroTango II Researcher Training Program and Ministerio de Economia y Competitividad (SPAIN) and the FEDER (project DPI2012-37466-CO3-03).Lespinard, A.; Bon Corbín, J.; Cárcel Carrión, JA.; Benedito Fort, JJ.; Mascheroni, RH. (2015). Effect of Ultrasonic-Assisted Blanching on Size Variation, Heat Transfer, and Quality Parameters of Mushrooms. Food and Bioprocess Technology. 8(1):41-53. https://doi.org/10.1007/s11947-014-1373-zS415381Aguirre, L., Frias, J. M., Barry-Ryan, C., & Grogan, H. (2009). Modelling browning and brown spotting of mushrooms (Agaricus bisporus) stored in controlled environmental conditions using image analysis. Journal of Food Engineering, 91, 280–286.Anantheswaran, R. C., Sastry, S. K., Beelman, R. B., Okereke, A., & Konanayakam, M. (1986). Effect of processing on yield, color, and texture of canned mushrooms. Journal of Food Science, 51(5), 1197–1200.Biekman, E. S. A., Kroese-Hoedeman, H. I., & Schijvens, E. P. H. M. (1996). Loss of solutes during blanching of mushrooms (Agaricus bisporus) as a result of shrinkage and extraction. Journal of Food Engineering, 28(2), 139–152.Biekman, E. S. A., van Remmen, H. H. J., Kroese-Hoedeman, H. I., Ogink, J. J. M., & Schijvens, E. P. H. M. (1997). Effect of shrinkage on the temperature increase in evacuated mushrooms (Agaricus bisporus) during blanching. Journal of Food Engineering, 33(1–2), 87–99.Brennan, M., Le Port, G., & Gormley, R. (2000). Post-harvest treatment with citric acid or hydrogen peroxide to extend the shelf life of fresh sliced mushrooms. Lebensmittel Wissenschaft und Technologie, 33, 285–289.Cárcel, J. A., Benedito, J., Rosselló, C., & Mulet, A. (2007). Influence of ultrasound intensity on mass transfer in apple immersed in a sucrose solution. Journal of Food Engineering, 78, 472–479.Cárcel, J. A., Benedito, J., Bon, J., & Mulet, A. (2007). High intensity ultrasound effects on meat brining. Meat Science, 76, 611–619.Cárcel, J. A., García-Pérez, J. V., Benedito, J., & Mulet, A. (2011). Food process innovation through new technologies: Use of ultrasound. Journal of Food Engineering, 110, 200–207.Cheng, X., Zhang, M., & Adhikari, B. (2013). The inactivation kinetics of polyphenol oxidase in mushroom (Agaricus bisporus) during thermal and thermosonic treatmemts. Ultrasonics Sonochemistry, 20, 674–679.Cliffe-Byrnes, V., & O’Beirne, D. (2007). Effects of gas atmosphere and temperature on the respiration rates of whole and sliced mushrooms (Agaricus bisporus): implications for film permeability in modified atmosphere packages. Journal of Food Science, 72, 197–204.Coskuner, Y., & Ozdemir, Y. (1997). Effects of canning processes on the elements content of cultivated mushrooms (Agaricus bisporus). Food Chemistry, 60(4), 559–562.Cruz, R. M. S., Vieira, M. C., Fonseca, S. C., & Silva, C. L. M. (2011). Impact of thermal blanching and thermosonication treatments on watercress (Nasturtium officinale) quality: thermosonication process optimisation and microstructure evaluation. Food and Bioprocess Technology, 4(7), 1197–1204.De Gennaro, L., Cavella, S., Romano, R., & Masi, P. (1999). The use of ultrasound in food technology I: inactivation of peroxidase by thermosonication. Journal of Food Engineering, 39, 401–407.De la Fuente, S., Riera, E., Acosta, V. M., Blanco, A., & Gallego-Juárez, J. A. (2006). Food drying process by power ultrasound. Ultrasonics, 44, 523–527.Delgado, A. E., Zheng, L., & Sun, D. W. (2009). Influence of ultrasound on freezing rate of immersion-frozen apples. Food and Bioprocess Technology, 2, 263–270.Devece, C., Rodríguez-López, J. N., Fenoll, J. T., Catalá, J. M., De los Reyes, E., & García-Cánovas, F. (1999). Enzyme inactivation analysis for industrial blanching applications: comparison of microwave, conventional, and combination heat treatments on mushroom polyphenoloxidase activity. Journal of Agricultural and Food Chemistry, 47(11), 4506–4511.Fernandes, F. A. N., & Rodrigues, S. (2007). Ultrasound as pre-treatment for drying of fruits: dehydration of banana. Journal of Food Engineering, 82, 261–267.Gabaldón-Leyva, C. A., Quintero-Ramos, A., Barnard, J., Balandrán-Quintana, R. R., Talamás-Abbud, R., & Jiménez-Castro, J. (2007). Effect of ultrasound on the mass transfer and physical changes in brine bell pepper at different temperatures. Journal of Food Engineering, 81, 374–379.Gallego-Juárez, J. A., Riera, E., De la Fuente, S., Rodríguez-Corral, G., Acosta-Aparicio, V. M., & Blanco, A. (2007). Application of high-power ultrasound for dehydration of vegetables: processes and devices. Drying Technology, 25, 1893–1901.Gamboa-Santos, J., Montilla, A., Soria, A. C., & Villamiel, M. (2012). Effects of conventional and ultrasound blanching on enzyme inactivation and carbohydrate content of carrots. European Food Research and Technology, 234, 1071–1079.García-Pérez, J. V., Cárcel, J. A., De la Fuente, S., & Riera, E. (2006). Ultrasonic drying of foodstuff in a fluidized bed. Parametric study. Ultrasonics, 44, 539–543.García-Pérez, J. V., Cárcel, J. A., Riera, E., Rosselló, C., & Mulet, A. (2012). Intensification of low-temperature drying by using ultrasound. Drying Technology, 30, 1199–1208.Gonzáles-Fandos, E., Giménez, M., Olarte, C., Sanz, S., & Simón, A. (2000). Effect of packaging conditions on the growth of microorganisms and the quality characteristics of fresh mushrooms (Agaricus bisporus) stored at inadequate temperatures. Journal of Applied Microbiology, 89, 624–632.Gormley, T. R. (1975). Chill storage of mushrooms. Journal of the Science of Food and Agriculture, 26, 401–411.Gouzi, H., Depagne, C., & Coradin, T. (2012). Kinetics and thermodynamics of thermal inactivation of polyfenol oxidase in an aqueous extract from Agaricus bisporus. Journal of Agricultural and Food Chemistry, 60, 500–506.Holdsworth, S. D. (1997). Thermal processing of packaged foods. London: Chapman Hall.Horžić, D., Jambrak, A. R., Belščak-Cvitanović, A., Komes, D., & Lelas, V. (2012). Comparison of conventional and ultrasound assisted extraction techniques of yellow tea and bioactive composition of obtained extracts. Food and Bioprocess Technology, 5, 2858–2870.Jambrak, A. R., Mason, T. J., Paniwnyk, L., & Lelas, V. (2007a). Ultrasonic effect on pH, electric conductivity, and tissue surface of button mushrooms, brussels sprouts and cauliflower. Czech Journal of Food Science, 25, 90–99.Jambrak, A. R., Mason, T. J., Paniwnyk, L., & Lelas, V. (2007b). Accelerated drying of button mushrooms, Brussels sprouts and cauliflower by applying power ultrasound and its rehydration properties. Journal of Food Engineering, 81, 88–97.Jasinski, E. M., Stemberger, B., Walsh, R., & Kilara, A. (1984). Ultra structural studies of raw and processed tissue of the major cultivated mushroom, Agaricus bisporus. Food Microstructure, 3, 191–196.Jolivet, S., Arpin, N., Wicher, H. J., & Pellon, G. (1998). Agaricus bisporus browning: a review. Mycological Research, 102, 1459–1483.Konanayakam, M., & Sastry, S. K. (1988). Kinetics of shrinkage of mushroom during blanching. Journal of Food Science, 53(5), 1406–1411.Kotwaliwale, N., Bakane, P., & Verma, A. (2007). Changes in textural and optical properties of oyster mushroom during hot air drying. Journal of Food Engineering, 78(4), 1207–1211.Leadley C. & Williams A. (2002). Power ultrasound—current and potential applications for food processing, Review No 32, Campden and Chorleywood Food Research Association.Lespinard, A. R., Goñi, S. M., Salgado, P. R., & Mascheroni, R. H. (2009). Experimental determination and modeling of size variation, heat transfer and quality indexes during mushroom blanching. Journal of Food Engineering, 92, 8–17.Lima, M., & Sastry, S. K. (1990). Influence of fluid rheological properties and particle location on ultrasound-assisted heat transfer between liquid and particles. Journal of Food Science, 55(4), 1112–1115.López, P., & Burgos, J. (1995). Peroxidase stability and reactivation after heat treatment and manothermosonication. Journal of Food Science, 60(3), 551–553.López, P., Sala, F. J., Fuente, J. L., Cardon, S., Raso, J., & Burgos, J. (1994). Inactivation of peroxidase lipoxigenase and phenol oxidase by manothermosonication. Journal of Agricultural and Food Chemistry, 42(2), 253–256.Mansfield, T. (1962). High temperature-short time sterilization. Proceedings First International Congress on Food Science and Technology, 4, 311–316.Mason T. J. (1998). Power ultrasound in food processing—the way forward. In M. J. W. Povey & T. J. Mason (Eds.), Ultrasound in Food Processing (pp 103–126). Blackie Academic & Professional, London.McArdle F. J. & Curwen D. (1962). Some factors influencing shrinkage of canned mushrooms. Mushroom Science, 5, 547–557.McArdle, F. J., Kuhn, G. D., & Beelman, R. B. (1974). Influence of vacuum soaking on yield and quality of canned mushrooms. Journal of Food Science, 39, 1026–1028.Mohapatra, D., Bira, Z. M., Kerry, J. P., Frías, J. M., & Rodrigues, F. A. (2010). Postharvest hardness and color evolution of White button mushrooms (Agaricus bisporus). Journal of Food Science, 75(3), 146–152.Ohlsson, T. (1980). Temperature dependence of sensory quality changes during thermal processing. Journal of Food Science, 45(4), 836–847.Ortuño, C., Martínez-Pastor, M., Mulet, A., & Benedito, J. (2013). Application of high power ultrasound in the supercritical carbon dioxide inactivation of Saccharomyces cerevisiae. Food Research International, 51, 474–481.Peralta-Jimenez, L., & Cañizares-Macías, M. P. (2012). Ultrasound-assisted method for extraction of theobromine and caffeine from cacao seeds and chocolate products. Food and Bioprocess Technology, 6, 3522–3529.Rodríguez-López, J. N., Fenoll, N. G., Tudela, J., Devece, C., Sánchez-Hernández, D., De los Reyes, D., et al. (1999). Thermal inactivation of mushroom polyphenoloxidase employing 2450 MHz microwave radiation. Journal of Agricultural Food Chemistry, 47, 3028–3035.Sala, F., Burgos, J., Condon, S., Lopez, P., & Raso, J. (1995). Effect of heat and ultrasound on microorganisms and enzymes. In G. W. Gould (Ed.), New methods of food preservation (1st ed., pp. 176–204). Glasgow: Blackie Academic and professional.Sanjuán, N., Hernando, I., Lluch, M. A., & Mullet, A. (2005). Effects of low temperature blanching on texture, microstructure and rehydration capacity of carrots. Journal of the Science of Food and Agriculture, 85, 2071–2076.Santos, M. V., & Lespinard, A. R. (2011). Numerical simulation of mushrooms during freezing using the FEM and an enthalpy—Kirchhoff formulation. Heat and Mass Transfer, 47, 1671–1683.Sastry, S. K., Beelman, R. B., & Speroni, J. J. (1985). A three-dimensional finite element model for thermally induced changes in foods: application to degradation of agaritine in canned mushrooms. Journal of Food Science, 50(5), 1293–1299.Sastry, S. K., Shen, G. Q., & Blaisdel, J. L. (1989). Effect of ultrasonic vibration on fluid-to-particule convective heat transfer coefficients. Journal of Food Science, 54(1), 229–230.Sensoy, I., & Sastry, S. K. (2004). Ohmic blanching of mushrooms. Journal of Food Process Engineering, 27(1), 1–15.Sheen, S., & Hayakawa, K. (1991). Finite difference simulation for heat conduction with phase change in an irregular food domain with volumetric change. International Journal of Heat and Mass Transfer, 34(6), 1337–1346.Simal, S., Benedito, J., Sanchez, E. S., & Rossello, C. (1998). Use of ultrasound to increase mass transport rates during osmotic dehydration. Journal of Food Engineering, 36, 323–336.Siró, I., Vén, C., Balla, C., Jónás, G., Zeke, I., & Friedrich, L. (2009). Application of an ultrasonic assisted curing technique for improving the diffusion of sodium chloride in porcine meat. Journal of Food Engineering, 91, 353–362.Soria, A. C., & Villamiel, M. (2010). Effect of ultrasound on the technological properties and bioactivity in foods: a review. Trends in Food Science and Technology, 21, 323–331.Verlinden, B. E., Yuksel, D., Baheri, M., De Baerdemaeker, J., & Van Dijk, C. (2000). Low temperature blanching effect on the changes in mechanical properties during subsequent cooking of three potato cultivars. International Journal of Food Science and Technology, 35, 331–340.Wu, C. M., Wu, J. L.-P., Chen, C.-C., & Chou, C.-C. (1981). Flavor recovery from mushroom blanching water. In G. Charalambous & G. Inglett (Eds.), The quality of foods and beverages: chemistry and technology, vol. 1. New York: Academic Press.Zivanovic, S., & Buescher, R. (2004). Changes in mushroom texture and cell wall composition affected by thermal processing. Journal of Food Science, 69, 44–48

An Evolutionary Conserved Role for Anaplastic Lymphoma Kinase in Behavioral Responses to Ethanol

Anaplastic lymphoma kinase (Alk) is a gene expressed in the nervous system that encodes a receptor tyrosine kinase commonly known for its oncogenic function in various human cancers. We have determined that Alk is associated with altered behavioral responses to ethanol in the fruit fly Drosophila melanogaster, in mice, and in humans. Mutant flies containing transposon insertions in dAlk demonstrate increased resistance to the sedating effect of ethanol. Database analyses revealed that Alk expression levels in the brains of recombinant inbred mice are negatively correlated with ethanol-induced ataxia and ethanol consumption. We therefore tested Alk gene knockout mice and found that they sedate longer in response to high doses of ethanol and consume more ethanol than wild-type mice. Finally, sequencing of human ALK led to the discovery of four polymorphisms associated with a low level of response to ethanol, an intermediate phenotype that is predictive of future alcohol use disorders (AUDs). These results suggest that Alk plays an evolutionary conserved role in ethanol-related behaviors. Moreover, ALK may be a novel candidate gene conferring risk for AUDs as well as a potential target for pharmacological intervention

La définition de l’obstruction bronchique par le rapport VEMS/CV : seuil fixe ou limite inférieure de la normale ?

International audienceIntroduction: While the screening of chronic obstructive lung diseases (COPD, asthma, etc.) constitutes a major public health issue in France and worldwide, simple spirometry appears currently as the key to meeting the challenge. Since description of the forced expiratory maneuver by Robert Tiffeneau in 1947, it has been admitted that the FEV1/VC ratio permits diagnosis obstructive pulmonary diseases. However, the diagnostic criteria for this ratio remain uncertain. The long-lasting debate between advocates of a 0.7 “fixed ratio” (FR) of 0.7 and advocates of the “lower limit of normal” (LLN) remains relevant.State of the arts: In this general review, we describe the respective advantages of the FR and LLN criteria according to the most recently published studies, and characterize the conditions associated with discrepancies between these criteria.Perspectives and conclusions: FR and LLN appear not to share similar diagnosis values and the use of both criteria facilitates proposal of an up-to-date interpretation and diagnosis strategy in the context of first-line spirometry, particularly for patients with FEV1/VC ratio in the “grey zone”Alors que le dépistage des maladies respiratoires obstructives chroniques (bronchopneumopathie chronique obstructive [BPCO], asthme, etc.) constitue un enjeu majeur de santé publique en France et dans le monde, la spirométrie simple est l’outil incontournable pour relever ce défi. Alors qu’il est établi depuis Robert Tiffeneau en 1947 que le rapport VEMS/CV permet le diagnostic de ces maladies chroniques obstructives, le critère diagnostique fait l’objet d’intenses débats entre partisans l’utilisation d’un « seuil fixe » de 0,7, et partisans de l’utilisation de la « limite inférieure de la normale ». Nous proposons dans cette revue narrative une présentation des avantages respectifs de ces deux critères diagnostiques, tenant compte des arguments les plus récents de la littérature, mais aussi des situations de discordance entre ces deux critères afin de proposer une stratégie d’interprétation et de diagnostic tenant compte de ces deux critères, dans le contexte d’une spirométrie de dépistage

Acute loss of lung function without wheezing during bee venom immunotherapy

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Impaired training-induced adaptation of blood pressure in COPD patients: implication of the muscle capillary bed

Fares Gouzi,1,2 Jonathan Maury,1,3 François Bughin,1,2 Marine Blaquière,1,2 Bronia Ayoub,1,2 Jacques Mercier,1,2 Antonia Perez-Martin,4,5 Pascal Pomiès,1 Maurice Hayot1,2 1PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, 2Department of Clinical Physiology, Montpellier University Hospital, Montpellier, 3Pulmonary Rehabilitation Center “La Solane”, 5 Santé Group, Osséja, 4Dysfunction of Vascular Interfaces Laboratory, EA 2992, University of Montpellier, 5Department of Vascular Medicine and Investigations, Nîmes University Hospital, Nîmes, France Background and aims: Targeting the early mechanisms in exercise-induced arterial hypertension (which precedes resting arterial hypertension in its natural history) may improve cardiovascular morbidity and mortality in COPD patients. Capillary rarefaction, an early event in COPD before vascular remodeling, is a potential mechanism of exercise-induced and resting arterial hypertension. Impaired training-induced capillarization was observed earlier in COPD patients; thus, this study compares the changes in blood pressure (BP) during exercise in COPD patients and matches control subjects (CSs) after a similar exercise training program, in relationship with muscle capillarization. Methods: Resting and maximal exercise diastolic pressure (DP) and systolic pressure (SP) were recorded during a standardized cardiopulmonary exercise test, and a quadriceps muscle biopsy was performed before and after training.Results: A total of 35 CSs and 49 COPD patients (forced expiratory volume in 1 second=54%±22% predicted) completed a 6-week rehabilitation program and improved their symptom-limited maximal oxygen uptake (VO2SL: 25.8±6.1 mL/kg per minute vs 27.9 mL/kg per minute and 17.0±4.7 mL/kg per minute vs 18.3 mL/kg per minute; both P<0.001). The improvement in muscle capillary-to-fiber (C/F) ratio was significantly greater in CSs vs COPD patients (+11%±9% vs +23%±21%; P<0.05). Although maximal exercise BP was reduced in CSs (DP: 89±10 mmHg vs 85±9 mmHg; P<0.001/SP: 204±25 mmHg vs 196±27 mmHg; P<0.05), it did not change in COPD patients (DP: 94±14 mmHg vs 97±16 mmHg; P=0.46/SP: 202±27 mmHg vs 208±24 mmHg; P=0.13). The change in muscle C/F ratio was negatively correlated with maximal exercise SP in CSs and COPD patients (r=-0.41; P=0.02). Conclusion: COPD patients showed impaired training-induced BP adaptation related to a change in muscle capillarization, suggesting the possibility of blunted angiogenesis. Keywords: angiogenesis, hypertension, pulmonary rehabilitatio

Specific muscle functional, morphological and angiogenic responses to exercise training in copd patients

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Optimisation des effets de la réhabilitation respiratoire chez des patients BPCO par une supplémentation en antioxydants : résultats d’essai randomisé contrôlé en double insu

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