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The effect of combining bone morphogenetic proteins -2 and -6 on osteoblastic differentiation and bone

Bone morphogenetic proteins-2 and -7 (BMP-2 and -7) are the only two members of the BMP subfamily approved to date to be used in combination with collagen type I in orthopedic surgery, although other BMPs have proven to also be highly osteoinductive. All the osteogenic BMPs signal through Smad-1/-5/-8 phosphorylation, but they have different preferences for the BMP receptors they use. Very high supraphysiological doses of BMPs have been used in the clinics for the treatment of non-union fractures and spinal fusions. Besides the high cost of these treatments, safety concerns have been recently raised. Hence there is an active field in finding alternatives to the most classical collagen + BMP-2 system. The aim of this work was to study the effect of combining two osteogenic BMPs (-2 and -6) belonging to different groups within the subfamily, and with different affinities to the existing BMP receptors. Both the growth and osteoblastic differentiation of MC3T3-E1 mouse preosteoblasts and rat bone marrow-derived mesenchymal stem cells (MSCs) under these conditions were studied, as well as in vivo ectopic bone formation when the BMPs were combined with collagen type I sponges. We show that the effect of these two growth factors is additive and that their combination might be helpful to accelerate in vivo osteogenesis while reducing the amount of each individual BMP used.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Robust Gaussian Filtering using a Pseudo Measurement

Many sensors, such as range, sonar, radar, GPS and visual devices, produce measurements which are contaminated by outliers. This problem can be addressed by using fat-tailed sensor models, which account for the possibility of outliers. Unfortunately, all estimation algorithms belonging to the family of Gaussian filters (such as the widely-used extended Kalman filter and unscented Kalman filter) are inherently incompatible with such fat-tailed sensor models. The contribution of this paper is to show that any Gaussian filter can be made compatible with fat-tailed sensor models by applying one simple change: Instead of filtering with the physical measurement, we propose to filter with a pseudo measurement obtained by applying a feature function to the physical measurement. We derive such a feature function which is optimal under some conditions. Simulation results show that the proposed method can effectively handle measurement outliers and allows for robust filtering in both linear and nonlinear systems

Bone marrow-derived mesenchymal stem cells characterization and transplantation in an animal model of congenital hydrocephalus

Congenital hydrocephalus is a disorder presenting a degeneration of the periventricular cerebral parenchyma and the white matter, which causes significant mortality and life-long neurological complications. There are currently no effective therapies for congenital hydrocephalus. Bone marrow-derived mesenchymal stem cells (BM-MSC) are considered as a potential therapeutic tool in neurodegenerative diseases, due to their ability to migrate to degenerated tissues and the production of growth factors. In the present study, using an animal model of congenital hydrocephalus, the hyh mouse, it has been studied the capacity of the BM-MSC to reach the degenerated regions exhibiting glial reactions and their probable neuroprotector effects. The BM-MSC were isolated from two different sources: a) transgenic mice expressing the monomeric red fluorescent protein (mRFP1); b) wild type mice. In the second case, the BM-MSC were labelled in vitro using bromodeoxyuridine, a fluorescent cell tracker and the lipophilic DiR. Before application, the cells were analysed using flow cytometry and immunofluorescence. The BM-MSC were injected into the retro-orbital sinus or into the lateral ventricle of hyh mice. After 24/96 hours of administration, the BM-MSC were detected under light, confocal and electron microscopes. The injected BM-MSC reached the degenerated periventricular regions and the disrupted neurogenic niches. They were detected in the periventricular parenchyma, around periventricular blood vessels and in the ventral meninges. Most of the applied BM-MSC expressed the glial cell-derived neurotrophic factor (GDNF), in the same way as the periventricular reactive astrocytes, suggesting a possible neuroprotector effect.FIS (Instituto de Salud Carlos III)-FEDER a AJJ. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Characterization and administration of bone marrow-derived mesenchymal stem cells in an animal model of congenital hydrocephalus

Bone marrow-derived mesenchymal stem cells (BM-MSC) are considered as a potential therapeutic tool in neurodegenerative diseases, due to their ability to migrate to degenerated tissues and the production of growth factors. Congenital hydrocephalus is a disorder characterized by a degeneration of the periventricular cerebral parenchyma and the white matter. In the present study, using an animal model of congenital hydrocephalus, the hyh mouse, it has been studied the capacity of the BM-MSC to reach the degenerated regions exhibiting glial reactions and their probable neuroprotector effects. The BM-MSC were isolated from two sources: a) transgenic mice expressing the monomeric red fluorescent protein (mRFP1); b) wild type mice. In the second case, the BM-MSC were labelled in vitro using bromodeoxyuridine, a fluorescent cell tracker and the lipophilic DiR. Before application, the cells were analysed using flow cytometry and immunofluorescence. The BM-MSC were injected into the retro-orbital sinus or into the lateral ventricle of hyh mice. After 24/96 hours of administration, they were detected under light, confocal and electron microscopes. The injected BM-MSC reached the degenerated periventricular regions and the disrupted neurogenic niches. They were detected in the periventricular parenchyma, around periventricular blood vessels and in the ventral meninges. Most of the applied BM-MSC expressed the glial cell-derived neurotrophic factor (GDNF), in the same way as the periventricular reactive astrocytes, suggesting a possible neuroprotector effect.Universidad de Málaga, Campus de Excelencia Internacional Andalucía Tech. Instituto de Salud Carlos III, PI12/0631 con cofinanciación FEDER

More than meets the eye: use of computer vision algorithms to identify stone tool material through the analysis of cut mark micro-morphology.

Artifcial intelligence algorithms have recently been applied to taphonomic questions with great success, outperforming previous methods of bone surface modifcation (BSM) identifcation. Following these new developments, here we try diferent deep learning model architectures, optimizers and activation functions to assess if it is possible to identify a stone tool?s raw material simply by looking at the cut marks that it created on bone. The deep learning models correctly discerned between fint, sandstone and quartzite with accuracy rates as high as 78%. Also, single models seem to work better than ensemble ones, and there is no optimal combination of hyperparameters that perform better in every possible scenario. Model fne-tuning is thus advised as a protocol. These results consolidate the potential of deep learning methods to make classifcations out of BSM?s microscopic features with a higher degree of confdence and more objectively than alternative taphonomic procedures.Agencia Estatal de Investigació

Explotación del fenómeno eurofán como oportunidad de negocio: un consumidor entregado

La figura del Eurofán cobra fuerza a finales de la década de los 90, un momento de decadencia para el Festival de la Canción de Eurovisión. Casi treinta años más tarde, este fenómeno se ha convertido en un movimiento de masas a nivel internacional, no solo europeo. Consolidándose como el programa no deportivo más visto del año, alcanzando los casi 200 millones de espectadores en el año 2015. El surgimiento de secuelas, como las preselecciones o las pre-parties, han provocado la aparición de una nueva oportunidad de negocio. Y es que, el objetivo principal de este Trabajo de Fin de Grado es el de rentabilizar el consumo del perfil eurofán mediante la creación de un festival de música en España.Grado en Publicidad y Relaciones Pública

The Autoimmune Tautology: An In Silico Approach

There is genetic evidence of similarities and differences among autoimmune diseases (AIDs) that warrants looking at a general panorama of what has been published. Thus, our aim was to determine the main shared genes and to what extent they contribute to building clusters of AIDs. We combined a text-mining approach to build clusters of genetic concept profiles (GCPs) from the literature in MedLine with knowledge of protein-protein interactions to confirm if genes in GCP encode proteins that truly interact. We found three clusters in which the genes with the highest contribution encoded proteins that showed strong and specific interactions. After projecting the AIDs on a plane, two clusters could be discerned: Sjögren's syndrome—systemic lupus erythematosus, and autoimmune thyroid disease—type1 diabetes—rheumatoid arthritis. Our results support the common origin of AIDs and the role of genes involved in apoptosis such as CTLA4, FASLG, and IL10