Repli-Fósil-3D: Aplicación técnicas de replicación 3D para la mejora de las colecciones utilizadas en la docencia práctica del área de Paleontología

En este proyecto se ha pretendido perfeccionar la docencia práctica de las asignaturas del ámbito de la Paleontología y de las actividades divulgativas impartidas por el departamento de Estratigrafía y Paleontología, y por lo tanto mejorar el grado de aprendizaje del alumnado, mediante el uso de modelos y réplicas impresas en 3D de diferentes grupos fósiles que, por diversos motivos (escasez de muestras en nuestros laboratorios, tamaño o fragilidad), no pueden ser correctamente observados y/o manipulados por el alumnado. Esto ha permitido al profesorado del área de Paleontología adaptar las prácticas docentes y actividades divulgativas a los requerimientos de la sociedad y universidad actuales.The aim of this project has been to improve the practical teaching of subjects in the field of Paleontology and in other dissemination activities carried out by the Department of Stratigraphy and Paleontology, in order to enhance the student learning. To do so, this project printed 3D models and replicas of different fossil groups which, for various reasons (scarcity of samples in our laboratories, size or fragility), cannot be correctly observed and/or manipulated by students. This has allowed the teaching staff of the Paleontology area to adapt their teaching practices and dissemination activities to the requirements of today's society and university

Análisis integrado del impacto de la variabilidad ambiental en las condiciones del fondo marino en el Mediterráneo durante el último Ciclo Glacial

The Last Glacial Cycle is one of the most interesting periods for environmental studies, presenting some of the most complete records of climatic and environmental changes that can be analogous to the current anthropogenic climate change. In addition, the Mediterranean area presents a highly interesting setting for palaeoceanographic, paleoclimatic and palaeoenvironmental studies, situated and impacted by both the north, middle and equatorial latitudes climate systems and presenting al the oceanographic characteristics of a big ocean with much faster reaction times. The layers rich in organic carbon, such as the sapropels in the Eastern Mediterranean Sea and their counterparts in the Western Mediterranean, the Organic Rich Layers (ORL), represent one of the most interesting phenomena within the recent geological record of the Mediterranean Sea Basin. These events have occurred over the past 3 million years as a consequence of the restriction of the waters of deep parts of the Mediterranean basins in response to climatic changes. This doctoral thesis presents a comprehensive analysis of these layers during the Last Glacial Cycle, with a particular focus on the ORLs, which have received less attention in past works, with the objective of deciphering the environmental changes and oceanographic and climatological triggers of these events in the Mediterranean. Additionally, a comparative examination between events in the West and East Mediterranean Sea basins is conducted, elucidating the temporal evolution of both basins and differences in the external factors leading to the deposition of these layers. In the present thesis, a multiproxy approach is employed to assess the stated objectives, integrating inorganic geochemistry and palaeontological proxies, in particular, the ichnological features observed on core surfaces. Novel ichnological analysis tools have been developed through image analysis, which have been applied in conjunction with traditional ichnological and geochemical analysis techniques on three cores from the Alboran Sea and one core from the Ionian Sea, near the Gulf of Sirte. Through the different projects completed during this thesis, some particular and general conclusions have been obtained. It has been observed that the relationship between ORLs and sapropels is intricate, and they generally respond asynchronously to climatic events, with no clear correlation between the bottom water conditions in the eastern and western events found, indicating a differential response to climatological variations over the Last Glacial Cycle. Sapropel depositions are more influenced by the African Monsoon cycles, while ORLs exhibit a more coherent response to the warm-cold cycles of the Last Glacial Period. Further, differences between the different ORLs and sapropels have been found, indicating variable conditions and important differences between the events that produced their deposition, with at least 3 main typologies of ORLs described. The utility of a multiproxy analysis, encompassing geochemical and paleontological data, in deep-sea core studies has been confirmed. Furthermore, the value of continuous ichnological analysis has been underscored in comparison with other indicators and in complementing other data in the analysis of marine sediment cores.Ministerio de Educación y Universidades (FPU17/01207) ; P18-RT-4074 (Junta de Andalucía

Análisis integrado del impacto de la variabilidad ambiental en las condiciones del fondo marino en el Mediterráneo durante el último Ciclo Glacial

The Last Glacial Cycle is one of the most interesting periods for environmental studies, presenting some of the most complete records of climatic and environmental changes that can be analogous to the current anthropogenic climate change. In addition, the Mediterranean area presents a highly interesting setting for palaeoceanographic, paleoclimatic and palaeoenvironmental studies, situated and impacted by both the north, middle and equatorial latitudes climate systems and presenting al the oceanographic characteristics of a big ocean with much faster reaction times. The layers rich in organic carbon, such as the sapropels in the Eastern Mediterranean Sea and their counterparts in the Western Mediterranean, the Organic Rich Layers (ORL), represent one of the most interesting phenomena within the recent geological record of the Mediterranean Sea Basin. These events have occurred over the past 3 million years as a consequence of the restriction of the waters of deep parts of the Mediterranean basins in response to climatic changes. This doctoral thesis presents a comprehensive analysis of these layers during the Last Glacial Cycle, with a particular focus on the ORLs, which have received less attention in past works, with the objective of deciphering the environmental changes and oceanographic and climatological triggers of these events in the Mediterranean. Additionally, a comparative examination between events in the West and East Mediterranean Sea basins is conducted, elucidating the temporal evolution of both basins and differences in the external factors leading to the deposition of these layers. In the present thesis, a multiproxy approach is employed to assess the stated objectives, integrating inorganic geochemistry and palaeontological proxies, in particular, the ichnological features observed on core surfaces. Novel ichnological analysis tools have been developed through image analysis, which have been applied in conjunction with traditional ichnological and geochemical analysis techniques on three cores from the Alboran Sea and one core from the Ionian Sea, near the Gulf of Sirte. Through the different projects completed during this thesis, some particular and general conclusions have been obtained. It has been observed that the relationship between ORLs and sapropels is intricate, and they generally respond asynchronously to climatic events, with no clear correlation between the bottom water conditions in the eastern and western events found, indicating a differential response to climatological variations over the Last Glacial Cycle. Sapropel depositions are more influenced by the African Monsoon cycles, while ORLs exhibit a more coherent response to the warm-cold cycles of the Last Glacial Period. Further, differences between the different ORLs and sapropels have been found, indicating variable conditions and important differences between the events that produced their deposition, with at least 3 main typologies of ORLs described. The utility of a multiproxy analysis, encompassing geochemical and paleontological data, in deep-sea core studies has been confirmed. Furthermore, the value of continuous ichnological analysis has been underscored in comparison with other indicators and in complementing other data in the analysis of marine sediment cores.El Último Ciclo Glacial es uno de los períodos más interesantes desde el punto de vista científico para el estudio de cambios paleoambientales. De este periodo se pueden encontrar algunos de los registros más completos de cambios climáticos y ambientales, los cuales se pueden equiparar como análogos del cambio climático antropogénico actual. Además, el área mediterránea se presenta como un escenario muy interesante para estudios paleoceanográficos, paleoclimáticos y paleoambientales, situada e impactada por los sistemas climáticos de latitudes norte, media y ecuatorial y presentando todas las características oceanográficas de un gran océano con tiempos de reacción mucho más rápidos. Las Capas Ricas en Carbono Orgánico, como los sapropeles del Este del Mar Mediterráneo y sus equivalentes del Oeste del Mediterráneo, conocidas como Organic Rich Layers (ORL) en su acepción inglesa, son uno de los eventos más interesantes que se pueden encontrar en el registro geológico reciente del Mar Mediterráneo. Estos eventos ocurrieron durante los últimos 3 millones de años como resultado del aislamiento de las partes profundas de las cuencas mediterráneas, impedida su renovación, un fenómeno que ocurre en respuesta a cambios oceanográficos inducidos por cambios climáticos. En esta tesis doctoral se ha realizado un análisis detallado de estos intervalos sedimentarios durante el Último Ciclo Glaciar, prestando una especial atención a las ORLs, las cuales habían sido menos estudiadas. También se realiza una comparación entre los eventos ocurridos en el Oeste y el Este del Mediterráneo, comprobando cómo se comportan ambas cuencas a lo largo del tiempo y analizando las diferencias en las causas que llevaron al depósito de estas capas. En esta tesis, para alcanzar los objetivos propuestos, se ha utilizado una aproximación multiindicador, combinando indicadores de geoquímica inorgánica y paleontología, especialmente información icnológica. Se han desarrollado nuevas herramientas de análisis icnológico a través del análisis de imágenes, las cuales se han integrado con otras técnicas tradicionales de análisis icnológico y geoquímico en 3 sondeos del Mar de Alboran y en un sondeo del Mar Jónico, cercano al golfo de Sidra. A través de los diferentes proyectos realizados durante esta tesis se han obtenido algunas conclusiones particulares y generales sobre las ORLs y la dinámica del mar Mediterráneo. Se ha observado que la relación entre ORL y sapropeles es compleja, respondiendo de forma general de forma asincrónica a eventos climáticos, no existiendo una correlación clara entre las condiciones del agua del fondo en los eventos orientales y occidentales estudiados. Por tanto, se observa una respuesta diferencial a las variaciones climatológicas durante el último Ciclo Glacial entre el este y el oeste del mar Mediterráneo. Los sapropeles están claramente controlados por los ciclos del monzón africano, mientras que los ORL exhiben una respuesta más coherente con los ciclos de transición rápida cálido-frío del último período glacial. Además, se han encontrado diferencias entre los diferentes ORL y sapropeles, lo que indica importantes diferencias en las condiciones del fondo marino durante la deposición de las diferentes capas, encontrándose al menos 3 tipologías principales de ORL atendiendo a sus características sedimentológicas y icnológicas. Se ha confirmado la utilidad de un análisis multi-indicador, que abarque datos geoquímicos y paleontológicos, en estudios de núcleos de aguas profundas. Además, se ha subrayado el valor del análisis icnológico continuo en comparación con otros indicadores y para complementar otros datos en el análisis testigos de sedimentos marinos.Tesis Univ. Granada. ; Ministerio de Educación y Universidades (FPU17/01207) ; P18-RT-4074 (Junta de Andalucía

Ichnological evidence for bottom water oxygenation during organic rich layer deposition in the westernmost Mediterranean over the Last Glacial Cycle

Research was funded by Projects CGL2015-66835-P, PID2019104624RB-I00 and PID2019-104625RB-100 (Secretaria de Estado de I + D + I, Spain), and B-RNM-072-UGR18, P18-RT-3804 and P18-RT4074 (Junta de Andalucia), and the Scientific Excellence Unit UCE2016-05 (Universidad de Granada). The research of SC-A is funded through a pre-doctoral grant, FPU, from the Ministerio de Educacion, Cultura y Deporte (Gobierno de Espana). The authors thank the Editor (Dr Rebesco) and both anonymous reviewers, whose comments helped improve the quality of this article.Organic rich layers (ORLs), deposited in the westernmost Mediterranean over the Last Glacial Cycle, have been studied integrating sedimentological and ichnological information from sediment records recovered at Ocean Drilling Program Leg 161 Sites 976 and 977. The conducted study has served to redefine the ORLs initially differentiated in sediment records from Sites 977 and 976, with seven new ORLs recognized, as well as extensions and subtraction of some parts in the ORLs previously defined. In addition, three different ORL types are distinguished according to sedimentological and ichnological features. Type 1 with intermediate thickness is highly bioturbated, mainly consisting of abundant Scolicia and Planolites, frequent Chondrites, and possible Thalassinoides in the base, which are interpreted as supporting dysoxic conditions during deposition. Type 2, corresponding to thicker intervals, shows alternance of highly to moderately bioturbated parts, revealing variable oxygen conditions -from moderate to extreme dysoxic or even suboxic. Type 3 consists of short, laminated intervals characterized by the absence of bioturbation, indicating anoxic or suboxic conditions and determining unfavourable macro benthic habitat. The amended ORLs show a correlation between the Sea Surface Temperatures and established climatic events over the Last Glacial Cycle in the Western Mediterranean.Junta de Andalucia B-RNM-072-UGR18 / P18-RT-3804 / P18-RT4074Secretaria de Estado de I + D + I, Spain CGL2015-66835-P / PID2019104624RB-I00 / PID2019-104625RB-100Universidad de Granada UCE2016-05Ministerio de Educacion, Cultura y Deporte (Gobierno de Espana

Pharmacological modulation of CXCR4 cooperates with BET bromodomain inhibition in diffuse large B-cell lymphoma

Constitutive activation of the chemokine receptor CXCR4 has been associated with tumor progression, invasion, and chemotherapy resistance in different cancer subtypes. Although the CXCR4 pathway has recently been suggested as an adverse prognostic marker in diffuse large B-cell lymphoma, its biological relevance in this disease remains underexplored. In a homogeneous set of 52 biopsies from patients, an antibody-based cytokine array showed that tissue levels of CXCL12 correlated with high microvessel density and bone marrow involvement at diagnosis, supporting a role for the CXCL12-CXCR4 axis in disease progression. We then identified the tetra-amine IQS-01.01RS as a potent inverse agonist of the receptor, preventing CXCL12-mediated chemotaxis and triggering apoptosis in a panel of 18 cell lines and primary cultures, with superior mobilizing properties in vivo than those of the standard agent. IQS-01.01RS activity was associated with downregulation of p-AKT, p-ERK1/2 and destabilization of MYC, allowing a synergistic interaction with the bromodomain and extra-terminal domain inhibitor, CPI203. In a xenotransplant model of diffuse large B-cell lymphoma, the combination of IQS-01.01RS and CPI203 decreased tumor burden through MYC and p-AKT downregulation, and enhanced the induction of apoptosis. Thus, our results point out an emerging role of CXCL12-CXCR4 in the pathogenesis of diffuse large B-cell lymphoma and support the simultaneous targeting of CXCR4 and bromodomain proteins as a promising, rationale-based strategy for the treatment of this disease

Pharmacological modulation of CXCR4 cooperates with BET bromodomain inhibition in diffuse large B-cell lymphoma

Constitutive activation of the chemokine receptor CXCR4 has been associated with tumor progression, invasion, and chemotherapy resistance in different cancer subtypes. Although the CXCR4 pathway has recently been suggested as an adverse prognostic marker in diffuse large B-cell lymphoma, its biological relevance in this disease remains underexplored. In a homogeneous set of 52 biopsies from patients, an antibody-based cytokine array showed that tissue levels of CXCL12 correlated with high microvessel density and bone marrow involvement at diagnosis, supporting a role for the CXCL12-CXCR4 axis in disease progression. We then identified the tetra-amine IQS-01.01RS as a potent inverse agonist of the receptor, preventing CXCL12-mediated chemotaxis and triggering apoptosis in a panel of 18 cell lines and primary cultures, with superior mobilizing properties in vivo than those of the standard agent. IQS-01.01RS activity was associated with downregulation of p-AKT, p-ERK1/2 and destabilization of MYC, allowing a synergistic interaction with the bromodomain and extra-terminal domain inhibitor, CPI203. In a xenotransplant model of diffuse large B-cell lymphoma, the combination of IQS-01.01RS and CPI203 decreased tumor burden through MYC and p-AKT downregulation, and enhanced the induction of apoptosis. Thus, our results point out an emerging role of CXCL12-CXCR4 in the pathogenesis of diffuse large B-cell lymphoma and support the simultaneous targeting of CXCR4 and bromodomain proteins as a promising, rationale-based strategy for the treatment of this disease