Osteocytes and Their Messengers as Targets for the Treatment of Multiple Myeloma

Osteocytes, the most abundant cells in the bone, orchestrate the function of osteoblasts and osteocytes to control physiological bone homeostasis. Accumulating evidence demonstrates that alteration of osteocyte function underlies the pathophysiology of several skeletal disorders, and that therapeutic targeting of factors produced by these cells improves skeletal health. Despite the advances in the knowledge of osteocyte biology, the contribution of these cells to the damaging effects of cancer in bone is practically unknown. Multiple myeloma is a plasma cell malignancy characterized by the presence of skeletal lesions and severe bone pain. Recent findings suggest that myeloma cells educate osteocytes to generate a microenvironment that is conducive to tumor progression, skeletal destruction, and bone pain. This review features some of these investigations and discusses the potential of targeting osteocytic pathways and osteocyte messengers for the treatment of multiple myeloma

Modelo de identificación de Meta-Topics a través de análisis semántico de conjuntos de datos extraídos de twitter

Las redes sociales se han vuelto cada vez m as importantes en los ultimos a~nos. Entre ellas destaca Twitter, donde los usuarios comparten opiniones y otros contenidos de forma p ublica. Dichas redes contiene grandes cantidades de informaci on oculta a simple vista. En este trabajo se pretende trabajar con datos obtenidos de Twitter y analizarlos para obtener informaci on relevante; para ello se va a hacer uso del an alisis sem antico, en pos de poder asociar los comentarios de los usuarios (o tweets) con temas m as generales (o meta-topics). Cabe destacar que, aunque cada vez existe un mayor n umero de trabajos dedicados a analizar este tipo de redes, el an alisis sem antico (como el llevado a cabo en este trabajo) de redes es todav a escaso, siendo lo m as cercano las t ecnicas de Topic Detection. Este trabajo trata de crear una aproximaci on al problema de la clasi caci on mediante an alisis sem antico, para ello se ha desarrollado un modelo que se centra en la detecci on de un unico meta-topics y que utiliza t ecnicas como LSA unidas a consultas sem anticas a DBpedia para obtener resultados con los que poder analizar la validez del modelo. Se han llevado a cabo pruebas con usuarios reales, que posteriormente han sido evaluados a mano para comprobar la e cacia de esta aproximaci on.Social Networks have become increasingly important over the last few years. One of the most relevant Social Network is Twitter. This Nework allows users to share public comment and contents. Social networks contain large amounts of hidden information. This work pretends to extract relevant data from Twitter and analyze them to obtain important information; In order to achieve this goal, we will apply semantic analysis to classify user comments (or tweets) on more general topics (or meta-topics). There are a large number of works devoted to analize social networks, however, semantic analysis is still scarce in this area,only Topic Detection techniques are applied in this context. This paper attempts to create a new approach to the problem of classi cation using semantic analysis. We have developed a model that focuses on the detection of a single meta-topic and use techniques such as LSA combined with semantic queries in DBpedia in order to obtain some results which can analyze the e ectiveness of the model. We have tested the model with real users, whose comments were subsequently evaluated to check the e ectiveness of this approach

“Don’t stop speaking”: Using game-based learning to promote fluency in the EFL classroom

Nowadays, one of the most important objectives is that our students learn in high school without seeing it as a punishment. This MA Thesis deals with an educational proposal “Don’t stop speaking” based on game-based learning to promote oral production, more specifically, fluency in the EFL classroom. It is a whole academic year educational proposal with one session per unit, in which I propose two types of sessions, an analogue and a digital one, for teachers to choose from. I want students to leave the routine by working cooperatively and using ICTs in the classroom. It would be possible to reduce the affective filter and achieve a more relaxed environment for students to learn and speak a foreign language, which is something that students are often afraid of.Una de las cosas más importantes hoy en día es que nuestros alumnos aprendan en los institutos sin verlo como un castigo. Este Trabajo de Fin de Máster presenta una propuesta educativa "Don't stop speaking" enfocada en el aprendizaje basado en el juego para promover la producción oral, más concretamente, la fluidez en el aula de inglés como lengua extranjera. Se trata de una propuesta educativa para todo el curso académico con una sesión por unidad, en la que propongo dos tipos de sesiones, una analógica y otra digital, para que los profesores puedan elegir. Quiero que los alumnos salgan de la rutina trabajando de forma cooperativa y utilizando las TICs en el aula. Se conseguiría reducir el filtro afectivo y lograr un ambiente más relajado para que los alumnos aprendan y hablen una lengua extranjera que es algo a lo que los alumnos temen a menudo.Máster en Profesor de Educación Secundaria Obligatoria y Bachillerato, Formación Profesional y Enseñanzas de Idioma

An Analysis on TED Talks: The Use of the Preposition and Conjunction ‘As’

Most of the studies dealing with the emerging oral genre of TED Talks have focused on the use of them as a way of teaching and learning, however, fewer studies have emphasized its structure or function. This essay deals with the study of different POS of the functional word as in different TED Talks being classified by their function and topic. More specifically, it is the study of the frequency and use of as as a preposition and conjunction on two sub-corpora with the help of the software Sketch Engine. It aims to show the process and selection criteria to compile a corpus, to study the usage of the preposition and conjunction as, and to manually analyze the errors that the software could be made. The results show that the preposition as is used to a higher extent in both sub-corpora, and consequently, in the whole specialized corpus. Keywords: As, TED Talk, corpus,La mayoría de los estudios que tratan el género oral en auge de las charlas TED se han centrado en el uso de éstas como forma de enseñanza y aprendizaje, sin embargo, son menos los estudios que se han centrado en su estructura o función. Este trabajo aborda el estudio de las diferentes categorías gramaticales de la palabra funcional “as” en diferentes charlas TED clasificadas por su función y temática. Más concretamente, se trata del estudio de la frecuencia y el uso de “as” como preposición y conjunción en dos sub-corpus con la ayuda del software Sketch Engine. El objetivo principal es mostrar el proceso y los criterios de selección para compilar un corpus, estudiar el uso de la preposición y la conjunción “as”, y analizar manualmente los errores cometidos por el software al analizar automáticamente los datos. Los resultados muestran que la preposición “as” se usa en un porcentaje mayor en ambos sub-corpus, y como resultado, en la totalidad del corpus especializado.Departamento de Filología InglesaGrado en Estudios Inglese

La autoestima de los niños víctimas de violencia intrafamiliar

La presente investigación bibliográfica está realizada con el objetivo de describir la autoestima de los niños víctimas de violencia intrafamiliar, la misma que está caracterizada por dos dimensiones importantes, que son la autoestima y la violencia intrafamiliar, las mismas que comprenden varias características. Siendo la autoestima el grado en que las personas expresan sentimientos ya sea de manera positiva o negativa acerca de sí mismos, es la capacidad que tienen de valorarse, amarse, apreciarse y aceptarse, la cual es importante porque condiciona el aprendizaje, facilita la superación de las dificultades personales, apoya la creatividad, determina la autonomía personal y posibilita una relación social saludable. Existen tres tipos de autoestima, la autoestima alta, la mediana y la baja. La violencia intrafamiliar es considerada como toda acción u omisión que consista en maltrato físico, psicológico, sexual y negligencia, hacia cualquier miembro de la familia siendo entendida como la forma de ejercer el poder mediante el empleo de la fuerza. Finalmente la autoestima de los niños se ve afectada por la violencia intrafamiliar pues son las víctimas más vulnerables, en las cuales las secuelas hacen grandes daños en el aspecto psicológico y físico que trascenderá en toda su vidaLicenciada en Psicología Educativa en la Especialización de Educación BásicaCuenc

Osteocytes and Skeletal Pathophysiology

For many years, osteocytes have been the forgotten bone cells and considered as inactive spectators buried in the bone matrix. We now know that osteocytes detect and respond to mechanical and hormonal stimuli to coordinate bone resorption and bone formation. Osteocytes are currently considered a major source of molecules that regulate the activity of osteoclasts and osteoblasts, such as RANKL and sclerostin; and genetic and pharmacological manipulations of either molecule markedly affect bone homeostasis. Besides playing a role in physiological bone homeostasis, accumulating evidence supports the notion that dysregulation of osteocyte function and alteration of osteocyte life-span underlies the pathophysiology of skeletal disorders characterized by loss bone mass and increased bone fragility, as well as the damaging effects of cancer in bone. In this review, we highlight some of these investigations and discuss novel observations that demonstrate that osteocytes, far from being passive cells entombed in the bone, are critical for bone function and maintenance

The Emerging Role of Osteocytes in Cancer in Bone

Advances in the last decade have established the osteocyte, the most abundant cell in bone, as a dynamic and multifunctional cell capable of controlling bone homeostasis by regulating the function of both osteoblasts and osteoclasts. In addition, accumulating evidence demonstrates that osteocyte function is altered in several skeletal disorders, and targeting osteocytes and their derived factors improves skeletal health. Despite the remarkable progress in our understanding of osteocyte biology, there has been a paucity of information regarding the role of osteocytes in the progression of cancer in bone. Exciting, recent discoveries suggest that tumor cells communicate with osteocytes to generate a microenvironment that supports the growth and survival of cancer cells and stimulates bone destruction. This review features these novel findings and discussions regarding the impact of chemotherapy on osteocyte function and the potential of targeting osteocytes for the treatment of cancer in bone. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

Sclerostin: an Emerging Target for the Treatment of Cancer-Induced Bone Disease

Purpose of Review This review provides a summary of the current knowledge on Sost/sclerostin in cancers targeting the bone, discusses novel observations regarding its potential as a therapeutic approach to treat cancer-induced bone loss, and proposes future research needed to fully understand the potential of therapeutic approaches that modulate sclerostin function. Recent Findings Accumulating evidence shows that sclerostin expression is dysregulated in a number of cancers that target the bone. Further, new findings demonstrate that pharmacological inhibition of sclerostin in preclinical models of multiple myeloma results in a robust prevention of bone loss and preservation of bone strength, without apparent effects on tumor growth. These data raise the possibility of targeting sclerostin for the treatment of cancer patients with bone metastasis. Summary Sclerostin is emerging as a valuable target to prevent the bone destruction that accompanies the growth of cancer cells in the bone. Further studies will focus on combining anti-sclerostin therapy with tumor-targeted agents to achieve both beneficial skeletal outcomes and inhibition of tumor progression

Direct cell-to-cell interactions between osteocytes and multiple myeloma (MM) cells up-regulate Sost and down-regulate OPG expression in osteocytes: evidence for osteocytic contributions to MM-induced bone disease

poster abstractOsteocytes are the most abundant bone cells, comprising more than 95% of the cells in bone. They are embedded into the bone matrix, but extensively communicate among themselves and with cells on the bone surface and the bone marrow through the osteocytic lacunar-canalicular network. Osteocytes secrete sclerostin, the product of the Sost gene, an antagonist of Wnt signaling that potently inhibits bone formation. Osteocytes are also a major source of pro- and anti-osteoclastogenic cytokines that regulate osteoclastogenesis and bone resorption, including RANKL and osteoprotegerin (OPG). Recent evidence suggests that the bone remodeling compartment is disrupted in multiple myeloma (MM) allowing close contact of MM cells with bone cells including osteocytes. However, the consequences of these interactions and the contribution of osteocytes to MM bone disease are unclear. Therefore, we determined if interactions between MM cells and osteocytes regulate osteocytic gene expression. We found that co-culture of murine MLO-A5 osteocytic cells with human JJN3 MM cells up-regulated murine Sost mRNA expression 2-3 fold as early as 4h, which remained elevated up to 24h. Consistent with Sost up-regulation induced by MM cells, the expression of OPG, a Wnt target gene, was decreased by 30-50% in MLO-A5 cells, resulting in an increased RANKL/OPG at 4h. Culture of JJN3 cells in the top and MLO-A5 cells in the bottom of Boyden chambers abolished both up-regulation of Sost and down-regulation of OPG mRNA expression in osteocytic cells, demonstrating the requirement of direct contact between MM cells and osteocytic cells. Human Sost and OPG mRNA transcripts were not detected in any of these experiments, demonstrating lack of contribution of MM JJN3 cells. These findings demonstrate that direct interactions between osteocytes and MM cells up-regulate the expression of the bone formation inhibitor Sost in osteocytes, which in turn decreases Wnt signaling, reduces osteocytic OPG expression increasing the RANKL/OPG ratio. We propose that increased Sost/Sclerostin expression contributes to the exacerbated bone resorption and the decreased bone formation that characterizes MM induced bone disease