Hypothalamic Regulation of Liver and Muscle Nutrient Partitioning by Brain-Specific Carnitine Palmitoyltransferase 1C in Male Mice

Carnitine palmitoyltransferase (CPT) 1C, a brain-specific protein localized in the endoplasmic reticulum of neurons, is expressed in almost all brain regions. Based on global knockout (KO) models, CPT1C has demonstrated relevance in hippocampus-dependent spatial learning and in hypothalamic regulation of energy balance. Specifically, it has been shown that CPT1C is protective against high-fat diet-induced obesity (DIO), and that CPT1C KO mice show reduced peripheral fatty acid oxidation (FAO) during both fasting and DIO. However, the mechanisms mediating CPT1C-dependent regulation of energy homeostasis remain unclear. Here, we focus on the mechanistic understanding of hypothalamic CPT1C on the regulation of fuel selection in liver and muscle of male mice during energy deprivation situations, such as fasting. In CPT1C-deficient mice, modulation of the main hypothalamic energy sensors (50 adenosine monophosphate-activated protein kinase, Sirtuin 1, and mammalian target of rapamycin) was impaired and plasma catecholamine levels were decreased. Consequently, CPT1C-deficient mice presented defective fasting-induced FAO in liver, leading to higher triacylglycerol accumulation and lower glycogen levels. Moreover, muscle pyruvate dehydrogenase activity was increased, which was indicative of glycolysis enhancement. The respiratory quotient did not decrease in CPT1CKO mice after 48 hours of fasting, confirming a defective switch on fuel substrate selection under hypoglycemia. Phenotype reversion studies identified the mediobasal hypothalamus (MBH) as the main area mediating CPT1C effects on fuel selection. Overall, our data demonstrate that CPT1C in the MBH is necessary for proper hypothalamic sensing of a negative energy balance and fuel partitioning in liver and muscle

Analysis of pattern recognition and dimensionality reduction techniques for odor biometrics

In this paper, we analyze the performance of several well-known pattern recognition and dimensionality reduction techniques when applied to mass-spectrometry data for odor biometric identification. Motivated by the successful results of previous works capturing the odor from other parts of the body, this work attempts to evaluate the feasibility of identifying people by the odor emanated from the hands. By formulating this task according to a machine learning scheme, the problem is identified with a small-sample-size supervised classification problem in which the input data is formed by mass spectrograms from the hand odor of 13 subjects captured in different sessions. The high dimensionality of the data makes it necessary to apply feature selection and extraction techniques together with a simple classifier in order to improve the generalization capabilities of the model. Our experimental results achieve recognition rates over 85% which reveals that there exists discriminatory information in the hand odor and points at body odor as a promising biometric identifier

Huella de carbono del reciclado en planta asfáltica en caliente con altas tasas de RAP

Este artículo describe un análisis de huella de carbono (Carbon Footprint) desarrollado para la valoración, desde un punto de vista ambiental, del empleo de RAP (Reclaimed Asphalt Pavement) en la fabricación y puesta en obra de mezclas asfálticas en caliente. El análisis se ha llevado a cabo de forma específica para materiales asfálticos a partir de una metodología de análisis de ciclo de vida (ACV) que ha considerado como unidad funcional la tonelada de mezcla asfáltica fabricada y colocada en obra, y como ecoindicador el kilogramo de CO2 equivalente. La metodología presentada, además de basarse en datos de consumos y emisiones reales, considera dos aspectos fundamentales desde el punto de vista ambiental: la durabilidad y la reciclabilidad de las soluciones estudiadas. Por último, se exponen los resultados obtenidos con la aplicación de esta metodología a distintos tipos de mezclas asfálticas recicladas y a otras producidas mediante el reciclado de mezclas asfálticas con elevado contenido de caucho de neumáticos fuera de uso

Adsorption of salmonella in clay minerals and clay-based materials

A series of clay minerals and clay-based materials have been tested to eliminate one of the most dangerous bacteria we can find in the water: Salmonella. It has been proven that the use of clays and their PCH materials can be a suitable method for removing Salmonella from water. The results of this initial study show that all the materials analyzed have great salmonella adsorption capacities ranging from the lowest value observed in the mont-PCH sample (0.29 × 1010 CFU g−1 ) to the highest value observed in the natural palygorskite sample (1.52 × 1010 CFU g−1 ). Macroporosity, accessible external surface area, and the presence of silanol groups in the external surface of the particles appears to be the controlling factors for Salmonella adsorption capacity while it seems that the structural characteristics of the clay minerals and their respective PCH does not affect the adsorption capacityThe authors wish to thank the project BIA2017-82391-R for the financial suppor

CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity

OBJECTIVE: Carnitine palmitoyltransferase 1C (CPT1C) is implicated in central regulation of energy homeostasis. Our aim was to investigate whether CPT1C in the ventromedial nucleus of the hypothalamus (VMH) is involved in the activation of brown adipose tissue (BAT) thermogenesis in the early stages of diet-induced obesity. METHODS: CPT1C KO and wild type (WT) mice were exposed to short-term high-fat (HF) diet feeding or to intracerebroventricular leptin administration and BAT thermogenesis activation was evaluated. Body weight, adiposity, food intake, and leptinemia were also assayed. RESULTS: Under 7 days of HF diet, WT mice showed a maximum activation peak of BAT thermogenesis that counteracted obesity development, whereas this activation was impaired in CPT1C KO mice. KO animals evidenced higher body weight, adiposity, hyperleptinemia, ER stress, and disrupted hypothalamic leptin signaling. Leptin-induced BAT thermogenesis was abolished in KO mice. These results indicate an earlier onset leptin resistance in CPT1C KO mice. Since AMPK in the VMH is crucial in the regulation of BAT thermogenesis, we analyzed if CPT1C was a downstream factor of this pathway. Genetic inactivation of AMPK within the VMH was unable to induce BAT thermogenesis and body weight loss in KO mice, indicating that CPT1C is likely downstream AMPK in the central mechanism modulating thermogenesis within the VMH. Quite opposite, the expression of CPT1C in the VMH restored the phenotype. CONCLUSION: CPT1C is necessary for the activation of BAT thermogenesis driven by leptin, HF diet exposure, and AMPK inhibition within the VMH. This study underscores the importance of CPT1C in the activation of BAT thermogenesis to counteract diet-induced obesity. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved. KEYWORDS: Brown adipose tissue; CPT1C; Diet-induced obesity; Hypothalamus; Thermogenesi

LH-21, a CB1 antagonist, reduces hepatotoxic damage produced by paracetamol overdose in a mice model.

Drug-induced liver injury (DILI) is one of the main causes of hepatic acute failure. Paracetamol can cause it when is ingested in excessive doses, leading to the depletion of the antioxidant mechanisms of the hepatocytes and a series of processes that conclude with cell death. One of the altered metabolic pathways is the endocannabinoid system (ECS), which has become a very interesting target to alleviate these events due to its involvement in inflammatory processes. For this reason, the triazole-derived compound LH-21, a cannabinoid receptor Cb1 antagonist, was used for the treatment of DILI in 8-week-old male C57BL/6 mice. In the present study, fasting mice were subjected to an oral overdose of paracetamol (300 mg/kg) and treated 2 hours later with 3 mg/kg of LH-21. After 24 hours, the animals were sacrificed and the livers were collected to determine the hepatic levels of metabolites related to antioxidant mechanisms, the expression of proteins involved in the generation of cellular damage and the transcription grade of the different components of the ECS. The observed results showed that LH-21 treatment raises GSH levels and total antioxidant capacity, in addition to reducing malondialdehyde values. Furthermore, the phosphorylation degree of Jnk and Stat3, as well as the activation status of Casp3, diminished. Regarding the ECS, the expression of Ppara, Cnr1, Cnr2 and Gpr55 did return to normal levels. This suggests that LH-21 effectively blocks the Cb1 activity, allowing the correct function of Ppar-α that promotes a cellular anti-inflammatory state and the relief of the symptoms produced by DILI. These results exhibit a promising perspective for the prevention or treatment of some toxic effects of paracetamol overdose with LH-21. Nevertheless, these findings are a first step to continue studying the involvement of the ECS in this type of liver disease and investigating the effectiveness of this Cb1 antagonist against the pathophysiology of DILI.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Mechatronic design, experimental setup, and control architecture design of a novel 4 DoF parallel manipulator

"This is an Author's Accepted Manuscript of an article published in [include the complete citation information for the final versíon of the article as published in the Mechanics Based Design of Structures and Machines 2018 [copyright Taylor & Francis], available online at: https://www.tandfonline.com/doi/10.1080/15397734.2017.1355249."[EN] Although parallel manipulators started with the introduction of architectures with six degrees of freedom, a vast number of applications require less than six degrees of freedom. Consequently, scholars have proposed architectures with three and four degrees of freedom, but relatively few four degrees of freedom parallel manipulators have become prototypes, especially of the two rotation and two translation motion types. In this article, we explain the mechatronics design, prototype, and control architecture design of a four degrees of freedom parallel manipulators with two rotation and two translation motions. We chose to design a four degrees of freedom manipulator based on the motion needed to complete the tasks of lower limb rehabilitation. To the author's best knowledge, parallel manipulators between three and six degrees of freedom for rehabilitation of lower limb have not been proposed to date. The developed architecture enhances the three minimum degrees of freedom required by adding a four degrees of freedom, which allows combinations of normal or tangential efforts in the joints, or torque acting on the knee. We put forward the inverse and forward displacement equations, describe the prototype, perform the experimental setup, and develop the hardware and control architecture. The tracking accuracy experiments from the proposed controller show that the manipulator can accomplish the required application.The authors wish to thank the Plan Nacional de I + D, Comision Interministerial de Ciencia y Tecnologia (FEDER-CICYT) for the partial funding of this study under project DPI2013-44227-R. We also want to thank the Fondo Nacional de Ciencia, Tecnologia e Innovacion (FONACIT-Venezuela) for its financial support under the project No. 2013002165.Vallés Miquel, M.; Araujo-Gómez, P.; Mata Amela, V.; Valera Fernández, Á.; Díaz-Rodríguez, M.; Page Del Pozo, AF.; Farhat, N. (2018). Mechatronic design, experimental setup, and control architecture design of a novel 4 DoF parallel manipulator. Mechanics Based Design of Structures and Machines. 46(4):425-439. https://doi.org/10.1080/15397734.2017.1355249S425439464Araujo-Gómez, P., Díaz-Rodriguez, M., Mata, V., Valera, A., & Page, A. (2016). Design of a 3-UPS-RPU Parallel Robot for Knee Diagnosis and Rehabilitation. 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(2003). Architecture optimization of a 3-DOF translational parallel mechanism for machining applications, the orthoglide. IEEE Transactions on Robotics and Automation, 19(3), 403-410. doi:10.1109/tra.2003.810242Clavel, R. (1988). A Fast Robot with Parallel Geometry. Proc. Int. Symposium on Industrial Robots, Lausanne, Switzerland, 91–100.Díaz, I., Gil, J. J., & Sánchez, E. (2011). Lower-Limb Robotic Rehabilitation: Literature Review and Challenges. Journal of Robotics, 2011, 1-11. doi:10.1155/2011/759764Díaz-Rodríguez, M., Mata, V., Valera, Á., & Page, Á. (2010). A methodology for dynamic parameters identification of 3-DOF parallel robots in terms of relevant parameters. Mechanism and Machine Theory, 45(9), 1337-1356. doi:10.1016/j.mechmachtheory.2010.04.007Escamilla, R. F., MacLeod, T. D., Wilk, K. E., Paulos, L., & Andrews, J. R. (2012). Cruciate ligament loading during common knee rehabilitation exercises. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 226(9), 670-680. doi:10.1177/0954411912451839Gan, D., Dai, J. S., Dias, J., Umer, R., & Seneviratne, L. (2015). Singularity-Free Workspace Aimed Optimal Design of a 2T2R Parallel Mechanism for Automated Fiber Placement. Journal of Mechanisms and Robotics, 7(4). doi:10.1115/1.4029957Garage, W. (2009). Robot Operating System. www.ros.org. Accessed date: August 2nd, 2017.Girone, M., Burdea, G., Bouzit, M., Popescu, V., & Deutsch, J. E. (2001). Autonomous Robots, 10(2), 203-212. doi:10.1023/a:1008938121020Gough, V., Whitehall, S. (1962). Universal Tyre Test Machine. Proceedings 9th Int. Technical Congress FISITA, London, vol. 117, 117–135.Jamwal, P. K., Hussain, S., & Xie, S. Q. (2013). Review on design and control aspects of ankle rehabilitation robots. Disability and Rehabilitation: Assistive Technology, 10(2), 93-101. doi:10.3109/17483107.2013.866986Lee, K.-M., & Arjunan, S. (1992). A Three Degrees of Freedom Micro-Motion In-Parallel Actuated Manipulator. Precision Sensors, Actuators and Systems, 345-374. doi:10.1007/978-94-011-1818-7_9Li, Y., & Xu, Q. (2007). Design and Development of a Medical Parallel Robot for Cardiopulmonary Resuscitation. IEEE/ASME Transactions on Mechatronics, 12(3), 265-273. doi:10.1109/tmech.2007.897257Mohan, S., Mohanta, J. K., Kurtenbach, S., Paris, J., Corves, B., & Huesing, M. (2017). Design, development and control of a 2PRP-2PPR planar parallel manipulator for lower limb rehabilitation therapies. Mechanism and Machine Theory, 112, 272-294. doi:10.1016/j.mechmachtheory.2017.03.001Ortega, R., & Spong, M. W. (1989). Adaptive motion control of rigid robots: A tutorial. Automatica, 25(6), 877-888. doi:10.1016/0005-1098(89)90054-xPierrot, F., Company, O. (1999). H4: A New Family of 4 DoF Parallel Robots. Proceedings of 1999 IEEE/ASME International Conference on Advanced Intelligent Mechatronics, Georgia, USA, 508–513.Ramsay, J. 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Simulación del soporte de escena en teatros andaluces

Se ha realizado una simulación de la acústica de la escena de cuatro teatro andaluces de proscenio. La cualidad de soporte de escena se ha estudiado mediante los parámetros acústicos de soporte inicial y final, promediados en frecuencia en las bandas de octava de 250-2000 Hz en varias posiciones individuales en las escenas. Se han ensayado dos tipologías diferentes (herradura y caja de zapatos) y dos disposiciones de escena según estuviese o no instalada la concha acústica. La comparación de los resultados obtenidos en la simulación y los valores experimentales medidos en un estudio previo han mostrado una buena concordancia entre ambos conjuntos de valores, apoyando así la validez del método informático de predicciónA simulation of the stage acoustics of four proscenium theatres in Andalusia (southern Spain) has been carried out. The quality of stage support has been studied using the early and late support acoustic parameters which are frequency-averaged in the 250-2000 Hz octave band range at various individual positions on the stages. Two different typologies (horseshoe and shoebox) and two configurations of the stage according to whether the orchestra shell is in-stalled are tested. The comparison between the results obtained in the simulation and the expe-rimental values measured in a previous study shows good agreement between both sets of values, thus supporting the validity of the method of computer predictio

Der p 1 based immunotoxin as potential tool for the treatment of dust mite respiratory allergy

Immunotoxins appear as promising therapeutic molecules, alternative to allergen-specifcimmunotherapy. In this work, we achieved the development of a protein chimera able to promote specifc cell death on efector cells involved in the allergic reaction. Der p 1 allergen was chosen as cell-targeting domain and the powerful ribotoxin α-sarcin as the toxic moiety. The resultant construction, named proDerp1αS, was produced and purifed from the yeast Pichia pastoris. Der p 1-protease activity and α-sarcin ribonucleolytic action were efectively conserved in proDerp1αS. Immunotoxin impact was assayed by using efector cells sensitized with house dust mite-allergic sera. Cell degranulation and death, triggered by proDerp1αS, was exclusively observed on Der p 1 sera sensitized-humRBL-2H3 cells, but not when treated with non-allergic sera. Most notably, equivalent IgE-binding and degranulation were observed with both proDerp1αS construct and native Der p 1 when using purifed basophils from sensitized patients. However, proDerp1αS did not cause any cytotoxic efect on these cells, apparently due to its lack of internalization after their surface IgEbinding, showing the complex in vivo panorama governing allergic reactions. In conclusion, herein we present proDerp1αS as a proof of concept for a potential and alternative new designs of therapeutic tools for allergies. Development of new, and more specifc, second-generation of immunotoxins following proDerp1αS, is further discussed

Derivation and validation of a blood biomarker score for 2-day mortality prediction from prehospital care: a multicenter, cohort, EMS-based study

Producción CientíficaIdentifying potentially life-threatening diseases is a key challenge for emergency medical services. This study aims at examining the role of different prehospital biomarkers from point-of-care testing to derive and validate a score to detect 2-day in-hospital mortality. We conducted a prospective, observational, prehospital, ongoing, and derivation—validation study in three Spanish provinces, in adults evacuated by ambulance and admitted to the emergency department. A total of 23 ambulance-based biomarkers were collected from each patient. A biomarker score based on logistic regression was fitted to predict 2-day mortality from an optimum subset of variables from prehospital blood analysis, obtained through an automated feature selection stage. 2806 cases were analyzed, with a median age of 68 (interquartile range 51–81), 42.3% of women, and a 2-day mortality rate of 5.5% (154 non-survivors). The blood biomarker score was constituted by the partial pressure of carbon dioxide, lactate, and creatinine. The score fitted with logistic regression using these biomarkers reached a high performance to predict 2-day mortality, with an AUC of 0.933 (95% CI 0.841–0.973). The following risk levels for 2-day mortality were identified from the score: low risk (score < 1), where only 8.2% of non-survivors were assigned to; medium risk (1 ≤ score < 4); and high risk (score ≥ 4), where the 2-day mortality rate was 57.6%. The novel blood biomarker score provides an excellent association with 2-day in-hospital mortality, as well as real-time feedback on the metabolic-respiratory patient status. Thus, this score can help in the decision-making process at critical moments in life-threatening situations.Junta de Castilla y León (Gerencia Regional de Salud - grant number GRS 1903/A/19 and GRS 2131/A/20)Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación/10.13039/501100011033/’, ERDF A way of making Europe, and Next GenerationEU/PRTR (under projects PID2020-115468RB-I00 and PDC2021-120775-I00)CIBER -Consorcio Centro de Investigación Biomédica en Red (Instituto de Salud Carlos III) (CB19/01/00012)Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL