Plasmatic Urea Nitrogen in Growing Rabbits with Different Combinations of Dietary Levels of Lysine, Sulphur Amino Acids and Threonine

[EN] Formulating diets to maximize nutrient harnessing has positive effects on performance and environment. In the case of growing rabbits, clues exist indicating that animals with high growth rate when consuming current diets show lower protein retention than expected, and it could be related to amino acid supply. The aim of this work is to find the amino acid combination (27 experimental diets: 3 levels of the 3 main limiting amino acids: lysine, sulphur amino acids, and threonine) that would minimize the nitrogen excretion in the bloodstream, a marker of the efficiency in the amino acid use This combination is a good candidate to be tested in order to improve performance and reduce pollution. A total of 27 experimental diets were formulated starting from the same basal mixture, with a moderate content of crude protein and digestible energy (155 g and 9.86 MJ/kg of digestible matter (DM), respectively, both estimated). The contents of lysine, sulphur amino acids and threonine were variable. The first one, close to the current recommendations (Medium, M; 8.1, 5.8 and 6.9 g/kg DM for lysine, sulphur amino acids and threonine, respectively), and two other levels were on average 15% higher (High, H; 9.4, 6.6 and 7.8 g/kg DM for lysine, sulphur amino acids and threonine, respectively) or lower (Low, L; 6.7, 4.9 and 5.7 g/kg DM for lysine, sulphur amino acids and threonine, respectively). Diets were named with three letters, indicating lysine, sulphur amino acids and threonine levels, respectively. In total, 918 weaned rabbits (28 days old) were used (34 per diet). At weaning, animals were fed ad libitum with a commercial diet until day 46, day 47 each collective cage was randomly switched to one experimental diet. At day 48, blood samples were collected at 08:00h then the animals were subjected to 10 h of fasting and a second blood sample was extracted at 21.00h. At 08:00h, Pasmatic urea nitrogen (PUN) was higher with the L level of lysine (p< 0.001), unaffected by the level of sulphur amino acids and increased with the level of threonine (p< 0.001). At 21:00h, minimum PUN was observed with the MHL diet (14.72 +/- 0.661 mg/dL). Taken into account the usual recommendations (established for a diet containing 11.3 MJ DE/kg DM, and then being 0.72, 0.51 and 0.61 g/MJ DE for lysine, sulphur amino acids and threonine, respectively), these results suggest that a diet containing more lysine and sulphur amino acids per energy unit (around 0.82 and 0.67 g/MJ DE) could better fit the growing rabbit requirements, although studies on the effects of such a diet on performance and protein retention are necessary.This study was supported by the Interministerial Commission for Science and Technology (CICYT) from the Spanish Government (AGL2017-85162-C2-1-R). The grant for Pablo Marin from the Ministry of Education, Culture and Sports (FPU-2014-01203) is also gratefully acknowledged.Marín-García, P.; López Luján, MDC.; Ródenas Martínez, L.; Martinez-Paredes, E.; Blas Ferrer, E.; Pascual Amorós, JJ. (2020). Plasmatic Urea Nitrogen in Growing Rabbits with Different Combinations of Dietary Levels of Lysine, Sulphur Amino Acids and Threonine. Animals. 10(6):1-8. https://doi.org/10.3390/ani10060946S18106Quevedo, F., Cervera, C., Blas, E., Baselga, M., & Pascual, J. J. (2006). Long-term effect of selection for litter size and feeding programme on the performance of reproductive rabbit does 2. Lactation and growing period. Animal Science, 82(5), 751-762. doi:10.1079/asc200688Pascual, M., Pla, M., & Blasco, A. (2008). Effect of selection for growth rate on relative growth in rabbits1,2. Journal of Animal Science, 86(12), 3409-3417. doi:10.2527/jas.2008-0976Pascual, M., & Pla, M. (2007). Changes in carcass composition and meat quality when selecting rabbits for growth rate. Meat Science, 77(4), 474-481. doi:10.1016/j.meatsci.2007.04.009Marín-García, P. J., Ródenas, L., Martínez-Paredes, E., Cambra-López, M., Blas, E., & Pascual, J. J. (2020). A moderate protein diet does not cover the requirements of growing rabbits with high growth rate. Animal Feed Science and Technology, 264, 114495. doi:10.1016/j.anifeedsci.2020.114495Carabaño R., Villamide M.J., García J., Nicodemus N., Llorente A., Chamorro S., & Menoyo D. (2010). New concepts and objectives for protein-amino acid nutrition in rabbits: a review. World Rabbit Science, 17(1). doi:10.4995/wrs.2009.664Taboada, E., Mendez, J., & de Blas, J. (1996). The response of highly productive rabbits to dietary sulphur amino acid content for reproduction and growth. Reproduction Nutrition Development, 36(2), 191-203. doi:10.1051/rnd:19960204Taboada, E., Mendez, J., Mateos, G. ., & De Blas, J. . (1994). The response of highly productive rabbits to dietary lysine content. Livestock Production Science, 40(3), 329-337. doi:10.1016/0301-6226(94)90099-xDe Blas, J. C., Taboada, E., Nicodemus, N., Campos, R., Piquer, J., & Méndez, J. (1998). Performance response of lactating and growing rabbits to dietary threonine content. Animal Feed Science and Technology, 70(1-2), 151-160. doi:10.1016/s0377-8401(97)00063-1Roth-Maier, D. A., Ott, H., Roth, F. X., & Paulicks, B. R. (2004). Effects of the level of dietary valine supply on amino acids and urea concentration in milk and blood plasma of lactating sows. Journal of Animal Physiology and Animal Nutrition, 88(1-2), 39-45. doi:10.1046/j.0931-2439.2003.00458.xDonsbough, A. L., Powell, S., Waguespack, A., Bidner, T. D., & Southern, L. L. (2010). Uric acid, urea, and ammonia concentrations in serum and uric acid concentration in excreta as indicators of amino acid utilization in diets for broilers. Poultry Science, 89(2), 287-294. doi:10.3382/ps.2009-00401Marín-García, P. J., López-Luján, M. del C., Ródenas, L., Martínez-Paredes, E. M., Blas, E., & Pascual, J. J. (2020). Plasma urea nitrogen as an indicator of amino acid imbalance in rabbit diets. World Rabbit Science, 28(2), 63. doi:10.4995/wrs.2020.12781Van Milgen, J., & Dourmad, J.-Y. (2015). Concept and application of ideal protein for pigs. Journal of Animal Science and Biotechnology, 6(1). doi:10.1186/s40104-015-0016-1Fernández-Carmona J., Blas E., Pascual J.J., Maertens L., Gidenne T., Xiccato G., & García. (2010). Recommendations and guidelines for applied nutrition experiments in rabbits. World Rabbit Science, 13(4). doi:10.4995/wrs.2005.516Real Decreto 53/2013, Por el Que se Establecen las Normas Básicas Aplicables Para la Protección de los Animales Utilizados en Experimentación y Otros Fines Científicos, Incluyendo la Docencia. BOE 34https://www.boe.es/diario_boe/txt.php?id=BOE-A-2013-1337Cifre, J., Baselga, M., García-Ximénez, F., & Vicente, J. S. (1998). Performance of a hyperprolific rabbit line I. Litter size traits. Journal of Animal Breeding and Genetics, 115(1-6), 131-138. doi:10.1111/j.1439-0388.1998.tb00336.xEstany, J., Camacho, J., Baselga, M., & Blasco, A. (1992). Selection response of growth rate in rabbits for meat production. Genetics Selection Evolution, 24(6), 527. doi:10.1186/1297-9686-24-6-527Bosch, L., Alegría, A., & Farré, R. (2006). Application of the 6-aminoquinolyl-N-hydroxysccinimidyl carbamate (AQC) reagent to the RP-HPLC determination of amino acids in infant foods. Journal of Chromatography B, 831(1-2), 176-183. doi:10.1016/j.jchromb.2005.12.002Eggum, B. O. (1970). Blood urea measurement as a technique for assessing protein quality. British Journal of Nutrition, 24(4), 983-988. doi:10.1079/bjn19700101Nicodemus, N., Mateos, J., Blas, J. C. de, Carabaño, R., & Fraga, M. J. (1999). Effect of diet on amino acid composition of soft faeces and the contribution of soft faeces to total amino acid intake, through caecotrophy in lactating doe rabbits. Animal Science, 69(1), 167-170. doi:10.1017/s1357729800051201García, A. I., de Bias, J. C., & Carabaño, R. (2004). Effect of type of diet (casein-based or protein-free) and caecotrophy on ileal endogenous nitrogen and amino acid flow in rabbits. Animal Science, 79(2), 231-240. doi:10.1017/s1357729800090093Monteiro-Motta, A. C., Scapinello, C., Oliveira, A. F. G., Figueira, J. L., Catelan, F., Sato, J., & Stanquevis, C. E. (2013). Levels of lysine and methionine+cystine for growing New Zealand White rabbits. Revista Brasileira de Zootecnia, 42(12), 862-868. doi:10.1590/s1516-3598201300120000

La diversidad en la Universidad: la innovación docente para la inclusión del alumno con discapacidad auditiva en el Grado de Odontología. (Continuación)

Se plantea en el presente proyecto un sistema de adaptación de las lecciones teóricas en tres asignaturas de 3º, 4º y 5º del Grado de Odontología, al lenguaje de signos o al texto subtitulado en relación a la explicación por parte del profeso

Plasma urea nitrogen as an indicator of amino acid imbalance in rabbit diets

[EN] In recent decades, recommendations on dietary protein content have been considerably reduced, while fibre content has been increased. Under these conditions, an adequate dietary amino acid balance could be crucial to optimise feed efficiency. Plasma urea nitrogen (PUN) level could be a good indicator of an amino acid imbalance and its potential has already been studied in other species, but not yet in rabbits. The main objective of the present work was to detect the possible interest of PUN in pinpointing amino acid deficiencies in rabbits. Two experimental diets were formulated from the same basal mixture, following all the recommendations for growing rabbits, except lysine, whose content was variable, following current guidelines in diet P8.1 or lower from those in P4.4 (with 8.1 and 4.4 g/kg dry matter of lysine and with 757 and 411 mg of lysine per MJ of digestible energy). Three different trials were designed: one where the animals were fed ad libitum (AL) and two others in which fasting periods of 10 h were included; one where feeding was restored at 08:00 h (Fast8h) and the other at 18:00 h (Fast18h). A total of 72 three-way crossbred growing rabbits (24 animals for each trial in a split-plot trial) up to a total of 12 recordings were used. Blood samples were taken every 4 h in AL trial and every hour after refeeding up to a total of six controls, in trials Fast8h and Fast18h. The differences between balanced and unbalanced diets in lysine were highest (P&lt;0.001) between 04:00 h and 12:00 h in animals fed ad libitum, and at 3 h after refeeding (21:00 h) in Fast18h. These results suggest that PUN could be an adequate indicator to detect deficiencies in amino acids in growing rabbitdiets.This study was supported by the Interministerial Commission for Science and Technology (CICYT) from the Spanish Government (AGL2017-85162-C2-1-R). The grant for Pablo Marín from the Ministry of Education, Culture and Sports (FPU2014-01203) is also gratefully acknowledged.Marín García, PJ.; López Luján, MDC.; Ródenas Martínez, L.; Martínez-Paredes, EM.; Blas Ferrer, E.; Pascual Amorós, JJ. (2020). Plasma urea nitrogen as an indicator of amino acid imbalance in rabbit diets. World Rabbit Science. 28(2):63-72. https://doi.org/10.4995/wrs.2020.12781OJS6372282AOAC. 2000. Official methods of analysis of the Association of Official Analytical Chemists, 18th ed. AOAC, Arlington, USA.Baselga M. 2004. Genetic improvement of meat rabbits. In Proc.: 8th World Rabbit Congress. September, 7-10, 2004, Puebla, México. 1: 1-13.Batey I.L. 1982. Starch analysis using thermostable alphaamylases. Starch, 34: 125-128. https://doi.org/10.1002/star.19820340407Bellier R., Gidenne T., Vernay M., Colin M. 1995. In vivo study of circadian variations of the cecal fermentation pattern in postweaned and adult rabbits. J. Anim. Sci. 73: 128-135. https://doi.org/10.2527/1995.731128xBlasco A. 1989. Genética y nutrición del conejo. In: de Blas C. (ed). Alimentación del conejo. Ediciones Mundi Prensa, Madrid, 1-15.Boletín Oficial del Estado. 2013. Real Decreto 53/2013, por el que se establecen las normas básicas aplicables para la protección de los animales utilizados en experimentación y otros fines científicos, incluyendo la docencia. BOE 34, 11370-11421.Bosch L., Alegría A., Farré R. 2006. Application of the 6-aminoquinolyl-N-hydroxysccinimidyl carbamate (AQC) reagent to the RP-HPLC determination of amino acids in infant foods. J. Chromatogr., 831: 176-183. https://doi.org/10.1016/j.jchromb.2005.12.002Brown J.A., Cline T.R. 1974. Urea excretion in the pig: an indicator of protein quality and amino acid requirements. J. Nutr., 104: 542-545. https://doi.org/10.1093/jn/104.5.542Carabaño R., de Blas J.C., García A.I. 2000. Recent advances in nitrogen nutrition in rabbits. World Rabbit Sci. 8: 14-28.Carabaño R., Piquer J., Menoyo D., Badiola I. 2010. The digestive system of the rabbit. In: de Blas C., Wiseman J. (ed). Nutrition of the Rabbit. CABI Publishing. CAB International, Wallingford, Oxon, UK, 1-18. https://doi.org/10.1079/9781845936693.0001Carabaño R., Villamide M.J., García J., Nicodemus N., Llorente A., Chamorro S., Menoyo D., García-Rebollar P., García-Ruiz A.I., De Blas, J.C. 2009. New concepts and objectives for proteinamino acid nutrition in rabbits. A review. World Rabbit Sci., 17: 1-14. https://doi.org/10.4995/wrs.2009.664Cartuche L., Pascual M., Gómez E.A., Blasco A. 2014. Economic weights in rabbit meat production. World Rabbit Sci., 22: 165-177. https://doi.org/10.4995/wrs.2014.1747Coma J., Carrion D., Zimmerman D.R. 1995. Use of plasma urea nitrogen as a rapid response criterion to determine the lysine requirement of pigs. J. Anim. Sci., 73: 472-481. https://doi.org/10.2527/1995.732472xComa J., Zimmerman D.R., Carrion D. 1996. Lysine requirement of the lactating sow determined by using plasma urea nitrogen as a rapid response criterion. J. Anim. Sci., 74: 1056-1062. https://doi.org/10.2527/1996.7451056xde Blas J.C., Gonzalez-Mateos G. 2010. Feed Formulation. In: de Blas C., Wiseman J. (ed). Nutrition of the Rabbit. second ed. CABI International. Wallingford, 222-232. https://doi.org/10.1079/9781845936693.0222de Blas C., Taboada E., Nicodemus N., Campos R., Piquer J., Méndez J. 1998. Performance response of lactating and growing rabbits to dietary threonine content. Anim. Feed Sci. Technol., 70: 151-160. https://doi.org/10.1016/S0377-8401(97)00063-1Donsbough A.L., Powell S., Waguespack A., Bidner T.D., Southern L. 2010. Uric acid, urea, and ammonia concentrations in serum and uric acid concentration in excreta as indicators of amino acid utilization in diets for broilers. Poult. Sci. 89: 287-294. https://doi.org/10.3382/ps.2009-00401Eggum B.O. 1970. Blood urea measurement as a technique for assessing protein quality. Br. J. Nutr., 24: 983-988. https://doi.org/10.1079/BJN19700101Feki S., Baselga M., Blas E., Cervera C., Gomez E.A. 1996. Comparison of growth and feed efficiency among rabbit lines selected for different objectives. Livest. Prod. Sci., 45: 87-92. https://doi.org/10.1016/0301-6226(95)00081-XForbes J.M. 2007. Voluntary Food Intake and Diet Selection. In: Farm Animals. CAB International, Wallingford, U.K, 226-246. https://doi.org/10.1079/9781845932794.0000Gidenne T., Lebas F., Fortun-Lamothe L. 2010. Feeding behaviour of rabbits. In: de Blas C., Wiseman J. (ed). Nutrition of the Rabbit. CABI International, Wallingford, 233-252. https://doi.org/10.1079/9781845936693.0233Gidenne T., Garreau H., Drouilhet L., Aubert C., Maertens L. 2017. Improving feed efficiency in rabbit production, a review on nutritional, technico-economical, genetic and environmental aspects. Anim. Feed Sci. Technol., 225: 109-122. https://doi.org/10.1016/j.anifeedsci.2017.01.016Hirakawa H. 2001. Coprophagy in leporids and other mammalian herbivores. Mam. Rev., 31: 61-80. https://doi.org/10.1046/j.1365-2907.2001.00079.xMaertens L., Cavani C., Petracci, 2010. Nitrogen and phosphorus excretion on commercial rabbit farms: calculations based on the input-output balance. World Rabbit Sci., 13: 3-16. https://doi.org/10.4995/wrs.2005.533Maertens L. 2009. Possibilities to reduce the feed conversion in rabbit production. In Proc.: Giornate di Coniglicoltura. Associazione Scientifica Italiana di Coniglicoltura. Forli. Italy. 1: 1-10.Marín-García P.J., Ródenas L., Martínez-Paredes E.M., Cambra-López M., Blas E., Pascual J.J. 2019. A moderate protein diet does not cover the requirements of growing rabbits with high growth rate. Anim. Feed Sci. Technol., 264: 114495. https://doi.org/10.1016/j.anifeedsci.2020.114495Marín-García P.J., Blas E., Cervera C., Pascual J.J. 2016. A deficient protein supply could be affecting selection for growth rate in rabbits. In. Proc., 68th Book of Abstracts of Annual Meeting of the European Federation of Animal Science. Belfast, UK, 1: 489.Mertens D.R. 2002. Gravimetric determination of amylase-treated neutral detergent fibre in feeds with refluxing beakers or crucibles: collaborative study. J. AOAC Int., 85: 1217-1240.Nicodemus N., Mateos J., de Blas C., Carabaño R., Fraga M.J. 1999. Effect of diet on amino acid composition of soft faeces and the contribution of soft faeces to total amino acid intake, through caecotrophy in lactating doe rabbits. Anim. Sci., 69: 167-170. https://doi.org/10.1017/S1357729800051201Prud'hon M., Chérubin M., Goussopoulos J., Carles Y. 1975. Évolution, au cours de la croissance, des caractéristiques de la consommation d'aliments solide et liquide du lapin domestique nourri ad libitum. Ann. 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Do Growing Rabbits with a High Growth Rate Require Diets with High Levels of Essential Amino Acids? A Choice-Feeding Trial

[EN] Two diets were designed to investigate the effect of the growth rate on amino acid requirements in growing rabbits: M diet (with medium levels of amino acids, following current nutritional recommendations for growing rabbits) and H diet (with high levels of lysine, sulphur amino acids and threonine compared with current nutritional recommendations). Performance, nutrient retention and digestibility (faecal and ileal) trials, as well as a choice-feeding test were conducted. We found no differences in animal performance, nutrient retention and digestibility parameters between diets, but the animals showed a preference for the M diet, expressed by a high intra-individual repeatability in preference. Our results provide useful information and nutrition tools to move towards precision protein nutrition in growing rabbits. As a consequence of the genetic selection process in growing rabbits, there are currently fast-growing animals exhibiting an average daily gain that may exceed 45 g/d. The protein requirements of these animals, namely amino acid requirements, may differ from animals with low growth rates. The objective of this work was to evaluate growth performance, the coefficient of total tract apparent digestibility (CTTAD), the apparent ileal digestibility (AID) of amino acids and nutrient retention of fast-growing rabbits when they had access to a diet with high levels of amino acids and/or a diet formulated with current nutritional recommendations in a choice-feeding trial. To this end, two diets were formulated: the M diet following current nutritional recommendations for growing rabbits (including 8.1, 5.8 and 6.9 g/kg dry matter (DM) of total lysine, sulphur amino acids and threonine, respectively) and the H diet with higher levels of total lysine, sulphur amino acids and threonine (9.4, 6.6 and 7.8 g/kg DM, respectively). A total of 220 weaned rabbits, from a paternal line selected for the growth rate, had free access to the M diet, the H diet or both (MH) diets from 28 to 63 days of age. The CTTAD of DM, crude protein and gross energy from 49 to 53 days of age as well as the AID of amino acids of the diets at 63 days of age were determined. Protein, amino acids and energy retained in the empty body from 28 to 63 days of age were also registered. No significant differences in growth performance, CTTAD, AID and nutrient retention between dietary treatments were observed. However, animals fed the H diet showed a higher AID of cysteine (p < 0.05) and higher threonine retention (p < 0.05) compared to the M diet. As regards the choice-feeding trial, MH animals showed a higher feed intake of the M diet compared to the H diet (+8.61%; p < 0.001), and furthermore, more than 50% of the animals preferred the M diet throughout the experimental period (p < 0.05). Our results suggest that animals with high growth rates do not show significantly higher productive traits when fed the H diet compared to the M diet. As regards choice feeding, MH animals were capable of choosing their preferred diet, showing high intra-individual repeatability in preference for the M diet. It would be interesting to continue studying this behaviour of choice based on amino acid levels.This research was funded by the Interministerial Commission for Science and Technology (CICYT; grant no. AGL2017-85162-C2-1-R).Marín-García, PJ.; López Luján, MDC.; Ródenas Martínez, L.; Martinez-Paredes, E.; Cambra López, M.; Blas Ferrer, E.; Pascual Amorós, JJ. (2021). Do Growing Rabbits with a High Growth Rate Require Diets with High Levels of Essential Amino Acids? A Choice-Feeding Trial. Animals. 11(3):1-13. https://doi.org/10.3390/ani11030824S11311

Expression of Inducible Nitric Oxide Synthase (iNOS) in Microglia of the Developing Quail Retina

Inducible nitric oxide synthase (iNOS), which produce large amounts of nitric oxide (NO), is induced in macrophages and microglia in response to inflammatory mediators such as LPS and cytokines. Although iNOS is mainly expressed by microglia that become activated in different pathological and experimental situations, it was recently reported that undifferentiated amoeboid microglia can also express iNOS during normal development. The aim of this study was to investigate the pattern of iNOS expression in microglial cells during normal development and after their activation with LPS by using the quail retina as model. iNOS expression was analyzed by iNOS immunolabeling, western-blot, and RT-PCR. NO production was determined by using DAR-4M AM, a reliable fluorescent indicator of subcellular NO production by iNOS. Embryonic, postnatal, and adult in situ quail retinas were used to analyze the pattern of iNOS expression in microglial cells during normal development. iNOS expression and NO production in LPS-treated microglial cells were investigated by an in vitro approach based on organotypic cultures of E8 retinas, in which microglial cell behavior is similar to that of the in situ retina, as previously demonstrated in our laboratory. We show here that amoeboid microglia in the quail retina express iNOS during normal development. This expression is stronger in microglial cells migrating tangentially in the vitreal part of the retina and is downregulated, albeit maintained, when microglia differentiate and become ramified. LPS treatment of retina explants also induces changes in the morphology of amoeboid microglia compatible with their activation, increasing their lysosomal compartment and upregulating iNOS expression with a concomitant production of NO. Taken together, our findings demonstrate that immature microglial cells express iNOS during normal development, suggesting a certain degree of activation. Furthermore, LPS treatment induces overactivation of amoeboid microglia, resulting in a significant iNOS upregulation.This work was supported by grants from Ministerio de Economía y Competitividad, Spain (BFU2010-19981) and Junta de Andalucía, Spain (P07-CVI-03008)

STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway

Background & Aims Besides their physiological role in bile formation and fat digestion, bile acids (BAs) synthesised from cholesterol in hepatocytes act as signalling molecules that modulate hepatocellular carcinoma (HCC). Trafficking of cholesterol to mitochondria through steroidogenic acute regulatory protein 1 (STARD1) is the rate-limiting step in the alternative pathway of BA generation, the physiological relevance of which is not well understood. Moreover, the specific contribution of the STARD1-dependent BA synthesis pathway to HCC has not been previously explored. Methods STARD1 expression was analyzed in a cohort of human non-alcoholic steatohepatitis (NASH)-derived HCC specimens. Experimental NASH-driven HCC models included MUP-uPA mice fed a high-fat high-cholesterol (HFHC) diet and diethylnitrosamine (DEN) treatment in wild-type (WT) mice fed a HFHC diet. Molecular species of BAs and oxysterols were analyzed by mass spectrometry. Effects of NASH-derived BA profiles were investigated in tumour-initiated stem-like cells (TICs) and primary mouse hepatocytes (PMHs). Results Patients with NASH-associated HCC exhibited increased hepatic expression of STARD1 and an enhanced BA pool. Using NASH-driven HCC models, STARD1 overexpression in WT mice increased liver tumour multiplicity, whereas hepatocyte-specific STARD1 deletion (Stard1ΔHep) in WT or MUP-uPA mice reduced tumour burden. These findings mirrored the levels of unconjugated primary BAs, β-muricholic acid and cholic acid, and their tauroconjugates in STARD1-overexpressing and Stard1ΔHep mice. Incubation of TICs or PMHs with a mix of BAs mimicking this profile stimulated expression of genes involved in pluripotency, stemness and inflammation. Conclusions The study reveals a previously unrecognised role of STARD1 in HCC pathogenesis, wherein it promotes the synthesis of primary BAs through the mitochondrial pathway, the products of which act in TICs to stimulate self-renewal, stemness and inflammation. Lay summary Effective therapy for hepatocellular carcinoma (HCC) is limited because of our incomplete understanding of its pathogenesis. The contribution of the alternative pathway of bile acid (BA) synthesis to HCC development is unknown. We uncover a key role for steroidogenic acute regulatory protein 1 (STARD1) in non-alcoholic steatohepatitis-driven HCC, wherein it stimulates the generation of BAs in the mitochondrial acidic pathway, the products of which stimulate hepatocyte pluripotency and self-renewal, as well as inflammation.We acknowledge support from grants PID2019-111669RB-100, SAF2017-85877R and SAF2015-73579-JIN from Plan Nacional de I+D funded by the Agencia Estatal de Investigación (AEI), the Fondo Europeo de Desarrollo Regional (FEDER) and CIBEREHD; the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA / NIH; as well as support from AGAUR of the Generalitat de Catalunya SGR-2017-1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network, the ‘ER stress-mitochondrial cholesterol axis in obesity-associated insulin resistance and comorbidities’-Ayudas FUNDACION BBVA and the Red Nacional 2018-102799-T de Enfermedades Metabólicas y Cáncer, and Project 201916/31 "Contribution of mitochondrial oxysterol and bile acid metabolism to liver carcinogenesis" 2019 by Fundació Marato TV3. We also acknowledge the support from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI16/00598, co-funded by European Regional Development Fund / European Social Fund, ‘Investing in your future’) and Centro Internacional sobre el Envejecimiento (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from R01 CA2344128 and U01 AA022614 grants to M.K.Peer reviewe

La diversidad en la Universidad: la innovación docente para la inclusión del alumno con discapacidad auditiva en el Grado de Odontología (DECO)

Depto. de Especialidades Clínicas OdontológicasFac. de OdontologíaFALSEsubmitte

Can High Levels of Hindrance Demands Increase the Worker’s Intellectual Response?

Job demands are factors that are associated with a physical and psychological cost when it comes to coping with them, but which can also positively affect the motivational process. Demands such as overload, defined as an excessive workload, have not presented positive results in any of the studies that have related it to employee engagement. The present study aims to delve into the possible positive effect of this demand on the intellectual bonding of employees. It is hypothesized that: (a) Initially, the increase in the perception of work overload will show a negative influence on the intellectual engagement of the employees; but (b) high perceptions of overload will change this effect, producing an increase in the intellectual dimension of engagement. The sample is made up of 706 employees of a Spanish multinational company. The results support this asymmetric curvilinear influence. The level of intellectual engagement is significantly reduced when the role overload increases from the lower values of the scale. However, upon reaching high levels of role overload, the intellectual engagement response begins to grow. These results challenge the conceptualization of overload as only negative and opens the door to consider that the positive response to a demand can also occur at high levels of it

Estudio para la implantación de Programas en Inglés en los títulos de grado de la ETSI Agrónomos de la Universidad Politécnica de Madrid

Universities are offering more and more courses and programmes in an additional language. At HEPCLIL, therefore, we would like to debate the methodological im - plications of these changes, giving voice to practical classroom experiences and initiatives. We would also like to act as a platform for cutting-edge research on CLIL in higher education. What impact does teaching in an additional language have on content or language learning? What are the effects on teachers and stu - dents in higher education

Desarrollo de estrategias discursivas de posicionamiento en los trabajos científicos universitarios (TFGs, TFMs, TDs, y AC): Análisis de los géneros discursivos, propuestas para la formación y elaboración de píldoras educativas

El presente proyecto reúne a docentes e investigadoras de dos grupos de investigación UCM consolidados del Departamento de Estudios Ingleses, “Discurso y comunicación en lengua inglesa: estudios de lingüística cognitiva y funcional” (DISCOM-COGFUNC) (930160) y “Lingüística funcional (ingles-español) y sus aplicaciones (FUNCAP)”, que imparten asignaturas afines. Todas las integrantes del equipo han formado parte al menos de uno de los dos proyectos de innovación previos, Innova-2015-188 e Innova-2016-123, sobre Objetos de Aprendizaje Reutilizable (OARs), como son las píldoras educativas, dando así muestra de una continuidad del trabajo en la innovación educativa en el campo de la docencia de lengua y lingüística inglesas. Los objetivos generales propuestos en la solicitud del proyecto han sido la formación de estudiantes y profesores en el uso y desarrollo de estrategias discursivas de posicionamiento en: (a) los trabajos científicos universitarios (TFGs, TFMs, TDs), y (b) los artículos de investigación de los docentes. Se trataba de llevar a cabo el análisis de estos géneros discursivos, realizar propuestas para la formación en el uso de estrategias discursivas, y elaborar materiales y píldoras educativas adecuadas a cada contexto de aprendizaje