Effects of brain insulin in conditioned place preference using exercise as a reward stimulus

Treball Final de Màster Universitari en Investigació en Cervell i Conducta. Codi: SBM024. Curs acadèmic: 2016/2017Researches suggest that physical activity is effective to prevent or treat stress-related psychiatric disorders such as depression, anxiety, and substance abuse disorders. Both, natural and drugs rewards is processed by the mesolimbic dopamine system; and also this is implicated to rewardrelated behavioral disorders. Studies supports the hypothesis that physical activity act as powerful natural stimulus of the mesolimbic system, using the conditioned place preference (CPP) paradigm with cues associates to voluntary exercise on the running wheel. On the other hand, several studies had reported that insulin can modulated aspects related to memory and learning, which are involved in reward-related behaviors, however, further data are necessary to understand these mechanisms. In addition, an important mediator of insulin/IGF1 (insulinlike growth factor-1) signaling is ERK (extracellular signal–regulated kinases). Evidence supports its implication in learning and memory, and is expressed in the NAcc and activated during exposure to natural and drugs rewards. Our hypothesis is that if insulin signaling can modulate preference to drugs via its effect on dopaminergic transmission in the mesolimbic system, it could similarly modulate preference to the context paired with voluntary exercise. In order to set up the behavior paradigm to study insulin/IGF1 signaling effect in preference for a rewarding stimulus such as exercise, male Wistar rats intraventricular insulin injections treated were used to study the rewarding effects on CPP paired to voluntary wheel running. pERK, IRS2, and IRS1 expression was assessed by immunohistochemical analysis. We found that intraventricular insulin injection showed no significant differences on conditioned place preference using exercise as a reward stimulus. pERK phosphorylation increases in specific brain regions of the insulin injected rats. IRS1 and IRS2 expression displays a different pattern in prefrontal cortex nucleus accumbens and ventral tegmental area. We suggest that the responses of animals in a CPP paradigm can be improved by insulin, due to insulin signaling into the reward areas. Data of immunohistochemical analysis support other studies that reported role of insulin into VTA neurons. Nevertheless, are needed additional research focus on the effects of insulin injections into mesolimbic regions as NAcc or VTA to understand what it is the role of insulin modulating reward-related behaviors

History of Education reforms in Spain.

This work provides a succinct historical overview of the history of the Spanish education system from 1812, date of the first Spanish Constitution, until 1970 at the end of the Francoist era in Spain, highlighting the legislative milestones and contextualising them within the larger political landscape in which they took place. The paper will go on to describe the basic legislation which has regulated the Spanish education system since 1970 describing some of their most significant aspects, from the General Education Law (LGE) of 1970 to the Organic Law Modifying the Organic Law for Education (LOMLOE) which came into force in 2020.post-print744 K

Studies of the thioredoxin system in redox signaling and oxidative stress

Reactive oxygen species exert reversible posttranslational modifications in proteins containing redox sensitive thiols, thereby affecting several cellular processes and protein functions. Reductive enzyme systems, such as the thioredoxin system, can reverse most of these cysteine modifications. Therefore, a tight control between oxidizing and reducing events is the central principle of redox signaling. The studies within this thesis have covered several aspects of the Trx system in the modulation of cellular signaling pathways. In Paper I, we evaluated how b-AP15, a small inhibitor of proteasome-associated DUB, exerts redox perturbations in tumor cells. It is known that b-AP15triggers an increase level of reactive oxygen species (ROS) and proteotoxic stress in can- cer cells. However, its efficacy inducing apoptosis diminished by antioxidants. To identify the precise mechanism by which b-AP15 induces redox perturbations, we generated cells deprived of mitochondrial DNA. We found that in cells lacking mitochondria, the oxidative stress generated by b-AP15 was completely abrogated. Furthermore, to exclude that the observed increase in the levels of oxidative stress were due to an inhibition of TrxR1, we evaluated a number of proteasome asso- ciated DUBs inhibitors that did not inhibit TrxR1. Similarly, to b-AP15 all the inhibitors tested induced oxidative stress and the expression of HO-1. In parallel, we observed mitochondrial dysfunction, measuring the levels of COX5b and TOMM34, in both cases their respective levels decreased in those cells treated with b-AP15. Based in all the results we could conclude that the source of ROS in cells treated with b-AP15 was of mitochondrial origin. In Paper II, we performed a drug-screen of compounds sharing a common enone motif with b-AP15 and many natural products with antineoplastic effect. Through biochemical and structural analyses, we could demonstrate the binding of the enone containing compounds to the proteasome-associated cysteine deubiquitinase, USP14, inhibiting its activity. Additionally, we further analyzed a subset of those compounds in a zebrafish embryo model where they showed antineoplastic activity. These findings suggest that DUB inhibition is a relatively common mode of action by cytotoxic compounds containing motifs and it helps to explain the antineoplastic effects of natural products containing such functional group. In Paper III, we identified HRI as a redox-regulated protein, which becomes oxidized when activated upon As(III) exposure. TrxR1 associates with HRI in cells and together with TRP14 and Trx1 reduces HRI in vitro. Moreover, several specific inhibitors of TrxR1 lead to HRI-dependent eIF2α phosphorylation, trans- lation suppression and stress granule formation. Based on our finding that HRI- mediated translation suppression is essential for cellular survival under conditions of high As(III), we revealed the Trx system as a regulator of the HRI dependent translational stress response. In Paper IV, we evaluated the role of TRP14 in the regulation of different redox- regulated transcriptional factors using our unique tool pTRAF (plasmid for tran- scription factor reporter activation based upon fluorescence). We discovered that using TRP14 knockdown HEK293 cells, NRF2 activation increased upon treat- ment with auranofin, we also uncovered that TRP14 is crucial for HIFactivation upon TNF-α stimulation in hypoxic conditions. Furthermore, endogenous TRP14 levels increased under hypoxia or TNF-α treatment, suggesting that TRP14 could itself be regulated by NFκB and HIF, which is compatible with the presence of the corresponding response elements in the proximal TXNDC17 promoter region. Surprisingly, using TRP14 knockout HEK293 cells we found that global protein translation was reduced, which could be reverted with methionine or N- acetylcysteine supplementation. TRP14 knockout cells were also, in contrast to controls, highly sensitive to PPG. We conclude that TRP14 has several roles in control of redox signaling pathways, and that TRP14 is the main intracellular reductase for liberation of cysteine from cystine. In Paper V, we de novo synthesized eight vinyl sulfone compounds and evalu- ated their capacity to activate NRF2, NFκB and HIF1 in comparison with DMF using our previously mention tool pTRAF. We selected a set of compounds that activate NRF2 more selectively than DMF and characterize their downstream effects using in vitro and in vivo models. Our selected compounds display a more selective oligodendrocyte associated effect which could be explore in the future as a regenerative drug in demyelinating disorders

Costes laborales unitarios en el éxito de las exportaciones alemanas (1999-2007)

The German commercial success is often associated to the strategy of internal devaluation that entailed a moderate wage growth. However, the main argument in this paper is that necessarily there have to be other important and different factors that explain the outstanding trade performance, especially the evolution of productivity derived from different export specializations between commercial partners. Therefore, the German export performance is studied in relation to the evolution of the unit labour costs focusing on both unit wages and productivity dynamics sorted by manufacturing branches and particularly in comparison with the four largest economies in the Euro Zone: Spain, Italy, France and the Netherlands. The main conclusion of the study is that the favourable German export dynamic was positively related to the development of unit labour costs primarily through the productivity performance and not via the evolution of wagesEl éxito comercial alemán se suele asociar a la estrategia de devaluación interna lograda a través de un crecimiento moderado de los salarios. Sin embargo, la principal hipótesis de la que se parte en este documento es que necesariamente tiene que haber otros factores que expliquen los buenos resultados comerciales de la economía alemana, destacando entre ellos la evolución de la productividad derivada de las diferencias de especialización exportadora que existen entre los socios comerciales. En consecuencia, se estudia la relación entre el comportamiento exportador alemán y la evolución de los costes laborales unitarios (prestando atención tanto al crecimiento de los salarios unitarios como a la evolución de la productividad) por ramas manufactureras. La contrastación se realiza tanto para las transacciones de Alemania con la Eurozona como para las registradas con las cuatro economías más importantes de la zona monetaria: España, Italia, Francia y los Países Bajos. La principal conclusión del estudio es que la favorable dinámica exportadora de Alemania estuvo positivamente relacionada con la evolución de los costes laborales unitarios principalmente a través del aumento de la productividad y no tanto del comportamiento de los salario

Virtues and values education in schools: a study in an international sample.

There is a deficit in character education research in Latin America and a lack of clarity about conceptual issues relevant to values and virtues. This lack of conceptual clarity has practical importance. The research sought to investigate empirically how school managers and teachers understand and practice character education, with particular attention to the distinction between educating values and virtues. The study was carried out during the first semester of 2022 on a sample of 160 schools in 17 countries, mainly in Christian schools in Spain and Mexico. The results show that there are differences according to the type of school and country. There are important findings regarding the concept of virtue and its relation to the concept of value, which virtues and values are most relevant for schools to teach, and which are the most used strategies in character education programmes. The research points to moral education as a central theme in schools, which considers both virtue and values education. There is a genuine interest on training teachers in virtue education.pre-print1755 K

The effect of teacher leadership on students’ purposeful learning.

Teaching leadership is a key factor for students’ learning and flourishing, and it occurs in an asymmetrical and interpersonal relationship. This research seeks to characterize the teaching leadership of high school teachers through the influence they exert on their students. It is not based on the teacher’s self-perception but on the experience that the students have had. For this purpose, a qualitative study was carried out in Spain with 200 first-year university students in which they answered four questions about the teacher who most influenced them during their high school. The results point to five leadership traits or styles that are not mutually exclusive: empathetic leadership, comforting leadership, motivating leadership, exemplary leadership, and wise leadership. In addition, moments of weakness and vulnerability in students are those that most favour the influence of the teacher in their lives, encouraging vital learning in them. This study highlights the importance of teacher leadership for student character education.post-print1771 K

高中教师的工作对大学生个人责任和关系责任的预测

Several studies have shown the importance of training students in responsibility. Responsibility implies taking responsibility for one’s own actions (personal responsibility) and, assuming that our actions affect others (relational responsibility). Teachers can and should help train students in this dimension. The aim of this research is to analyze and understand which teaching behaviors and actions favor the formation of personal and relational responsibility in university students. The research design was sequential explanatory (mixed methodology). There were 403 university students for the quantitative study and 200 for the qualitative study. The measurement instrument used was designed and validated ad hoc. It presented adequate reliability and validity indicators. In addition, the ERRP scale was used, which assesses the personal and relational responsibility of the university student. The opinion of the participants was collected from open questions included in the questionnaire used. The results show that 14.4% of the students’ personal and relational responsibility can be explained by the teaching actions that contribute to it. The qualitative study shows that relational responsibility learning is higher than personal responsibility learning. A reliable and valid scale is provided to assess teachers’ actions that shape students’ personal and relational responsibility as well as teachers’ actions and behaviors that can help to elaborate a formative ethical competence on it.Diversos estudios han mostrado la importancia de formar a los estudiantes en responsabilidad lo que implica, hacerse cargo de las propias acciones (responsabilidad personal) y asumir que nuestras acciones afectan a los demás (responsabilidad relacional). Los docentes pueden y deben ayudar a formar a los estudiantes en esta dimensión. La investigación tiene como objetivo analizar y comprender qué comportamientos y acciones docentes favorecen la formación de la responsabilidad personal y relacional en los universitarios. El diseño de investigación fue secuencial explicativo (metodología mixta). Se contó con 403 estudiantes universitarios para el estudio cuantitativo y con 200 para el estudio cualitativo. El instrumento de medida empleado fue diseñado y validado ad hoc. Este presentó indicadores de fiabilidad y validez adecuados. Además, se empleó la escala ERRP que valora la responsabilidad personal y relacional del estudiante universitario. La opinión de los participantes fue recogida a partir de preguntas abiertas incluidas en el cuestionario utilizado. Los resultados muestran que el 14.4% de la responsabilidad personal y relacional de los estudiantes se puede explicar por las acciones docentes que contribuyen a la misma. El estudio cualitativo muestra que los aprendizajes de la responsabilidad relacional son mayores que los de la responsabilidad personal. Se aporta una escala fiable y válida que permite valorar las acciones de los docentes que forman la responsabilidad personal y relacional de los estudiantes así como acciones y comportamientos docentes que pueden ayudar a elaborar una competencia ética formativa sobre la misma.Ряд исследований показывает важность обучения учащихся ответственности, что подразумевает принятие ответственности за свои действия (личная ответственность) и принятие того, что их действия влияют на других (коллективная ответственность). Учителя могут и должны помочь в подготовке учащихся в этом аспекте. Цель исследования - проанализировать и понять, какое поведение и действия преподавателя способствуют формированию личной и коллективной ответственности у студентов университета. Дизайн исследования - последовательный разъяснительный (смешанная методология). В количественном исследовании приняли участие 403 студента университета, в качественном - 200. Используемый инструмент измерения был разработан и валидирован ad hoc. Он имел адекватные показатели надежности и валидности. Кроме того, использовалась шкала ERRP, оценивающая личную и коллективную ответственность студента университета. Мнение участников было собрано с помощью открытых вопросов, включенных в анкету. Результаты показали, что 14,4% личной и реляционной ответственности студентов можно объяснить действиями преподавателей, которые способствуют ее развитию. Качественное исследование показывает, что обучение коллективной ответственности выше, чем обучение личной ответственности. Предлагается надежная и валидная шкала для оценки действий преподавателей, формирующих личную и коллективую ответственность учащихся, а также действий и поведения преподавателей, которые могут помочь в развитии формируемой этической компетентности в этой области.各种研究表明培养学生责任感的重要性，这意味着对自己的行为负责（个人责任）并假设我们的行为会影响他人（关系责任）。教师可以而且应该在这个维度上帮助培养学生。该研究的目的是分析和了解哪些行为和教学行为有利于大学生个人和关系责任的形成。 研究采用解释性顺序（混合方法）设计。对 403 名大学生进行了定量研究，200 名大学生进行了定性研究。使用的测量仪器是专门设计和验证的。这提供了足够的可靠性和有效性指标。此外，还使用了 ERRP 量表，该量表评估大学生的个人和关系责任。参与者的意见是从所用问卷中包含的开放性问题中收集的。结果表明，学生的个人和关系责任中有 14.4% 可以用促成它的教学行为来解释。定性研究表明，关系责任的学习大于个人责任的学习。 本研究提供了一个可靠和有效的量表，允许评估教师的行为，这些行为促使学生的个人和关系责任的形成，以及有助于发展形成性道德能力的行为和教师行为

Plan de mantenimiento para línea de envasado de la viña Cremaschi Furlotti

101 p.La siguiente memoria se presenta a la viña Cremaschi Furlotti, como el primer paso para la creación de un plan de mantenimiento preventivo que facilite los canales de información. Debido a que el plan de mantenimiento actual, se basa en el mantenimiento correctivo y solo consta de inspecciones mensuales. Es por esto que se ha propuesto a la empresa comenzar con un plan de mantenimiento base, que comience en el o los equipos de mayor criticidad dentro de la línea de envasado y que permita adherir los demás equipos. Es por esto que el proyecto comenzara determinando el o los equipos que servirán como base para crear un plan de mantenimiento, estos se elegirán mediante un análisis de criticidad el cual arrojara los equipos más críticos dentro de la línea de envasado. Luego estos equipos se analizaran mediante un análisis de modo de falla efecto y criticidad (FMECA), donde se jerarquizara y determinaran los puntos críticos del equipo, a los cuales se destinaran mayores atenciones y recursos. Terminando con la creación del plan de mantenimiento, el cual planificara todas las órdenes de trabajo en un calendario de mantenimiento anual, donde las ordenes de trabajo de inspección, lubricación y mantenimiento general, serán almacenadas en un registro de mantenimiento el cual ayudara al encargado a organizar las tareas semanales de los equipos. Junto a esto se realizaron planillas para visualizar los procedimientos básicos y necesarios para el equipo, además de los estándares de mantenimiento Con este plan de mantenimiento se busca poder organizar las funciones y así mostrar las tareas para cumplir con la exigencias de las normas BRC y ISF, las cuales certifican la calidad e inocuidad de alimentos, que comercializa la viña Cremaschi Furlotti, y que permitirán a la viña vender sus productos en el mercado exterior./ ABSTRACT: The following memory presents the Cremaschi Furlotti winery as the first step to create a preventive maintenance plan that facilitates the information channels. On account that the current maintenance plan is based on the corrective maintenance and only comprises monthly inspections. Due to this fact, it has been proposed to the company to start with a base maintenance plan, which starts in the most critical equipment within the line of bottling and that allows bonding the rest of the equipment. Therefore, the project will start determining the equipment that will work as base to create a maintenance plan, these will be chosen through a criticality analysis, which will deliver the most critical equipment within the bottling line. Subsequently, the equipment will be examined through a Failure Mode, Effect, and Criticality Analysis (FMECA), where the critical points of the equipment will be ranked and determined, which will be destined with higher attention and resources. Finishing the creation of the maintenance plan, which will plan all the working orders in an annual schedule of maintenance, where the orders of inspection work, lubrication, and general maintenance will be stored in a maintenance register that will help the person in charge to organize weekly tasks of the equipment. Besides, spreadsheets have been realized to visualize the basic and necessary procedure for the equipment, in addition to the maintenance standards. With this maintenance plan it is intended to be able to organize the functions so that it can be shown the tasks to accomplish the requirements of the BRC and ISF norms, which certify the quality and innocuousness of foodstuffs that the Cremaschi Furlotti winery commercializes and that will allow the company to sell its products in the foreign trade

Diseño de una metodología para la implementación de cuentas que controlen los costos y gastos ambientales en el sector de la construcción y mantenimiento de vías. Caso: Empresa de Pavimentos y Construcciones Viales PCV Cía. Ltda.

Today, environmental accounting has become important for companies because issues such as environmental pollution have been becoming an increasingly serious worldwide economic, social and political problem. At the national and international plan is being taken to protect the environment and reduce, prevent and mitigate the effects of pollution. Consequently, companies currently have a tendency to disseminate among the wider community information about their policies, objectives and programs, costs and benefits associated with such policies, objectives and programs and on environmental risks and measures taken in this regard. That is why this paper we address the issue design manual recording of expense accounts and environmental expenditure PCV Road Pavements and Construction Co. Company. Ltda. And his relationship with environmental facts in order to show an example of how to include in the financial statements and related notes accounting operations and events related to the environment.Hoy en día la contabilidad ambiental ha cobrado importancia para las empresas porque cuestiones tales como la contaminación ambiental se han ido convirtiendo en un problema económico, social y político cada vez más grave en todo el mundo. En el plan nacional e internacional se están adoptando medidas para proteger el medio ambiente y reducir, evitar y mitigar los efectos de la contaminación. En consecuencia, actualmente las empresas tienen tendencia a divulgar entre la comunidad en sentido amplio la información sobre sus políticas, objetivos y programas ambientales , sobre los gastos y beneficios relacionados con tales políticas ,objetivos y programas , y sobre los riesgos ambientales y las medidas que adoptan al respecto. Es por ello que este trabajo abordamos el tema diseño del manual para registro de las cuentas de costo y gasto ambiental de la Empresa Pavimentos y Construcciones Viales PCV Cía. Ltda. Y su relación con los hechos ambientales, con el fin de mostrar un ejemplo de cómo incluir en los estados financieros y en las notas conexas la contabilidad de las operaciones y los acontecimientos relacionados con el medio ambiente