Linces en el paleártico: variación genómica en poblaciones pasadas y presentes

Programa de Doctorado en Medio Ambiente y SociedadLínea de Investigación: Biodiversidad y Biología de la ConservaciónClave Programa: DAMCódigo Línea: 83Distintas fuerzas evolutivas, como migración, mutación, flujo génico, selección y deriva, actúan en las poblaciones provocando cambios en frecuencias alélicas que se acaban consolidando como divergencias nucleotídicas, algunas de las cuales pueden sustentar divergencias adaptativas. La acumulación de estos cambios evolutivos termina diferenciando genéticamente las poblaciones y generando linajes y, eventualmente, especies. A lo largo de este continuo, eventos naturales, como las fluctuaciones climáticas y antrópicos alteran la demografía de estas especies y el equilibrio entre las fuerzas evolutivas y generan patrones genómicos, que nos informan sobre la historia evolutiva del linaje. En esta tesis, usamos nuevos desarrollos metodológicos en el área de la genómica y el ADN antiguo para ahondar en el conocimiento de la historia evolutiva de las dos especies de lince del paleártico, el lince boreal (Lynx lynx) y el lince ibérico (Lynx pardinus), que a pesar de presentar rasgos de vida similares, tienen historias demográficas, en apariencia, muy dispares. El lince boreal se considera una especie de preocupación menor en cuanto a conservación y tiene una distribución muy amplia en Eurasia, mientras que el lince ibérico, distribuido en un par de poblaciones al sur de la península ibérica, ha sido considerado el felino más amenazado del mundo. Específicamente, en esta tesis, vamos a describir los patrones genómicos de poblaciones presentes y pasadas de ambas especies para reconstruir su historia evolutiva, e investigar el rol que distintas fuerzas evolutivas, cambios demográficos y factores extrínsecos han jugado en el moldeado de sus genomas a lo largo del tiempo. En el capítulo 1 el uso de 80 genomas completos de lince boreal distribuidos a lo largo de su área de distribución en Asia y Europa, nos permite caracterizar los patrones biogeográficos de la especie hoy día y relacionarlos con eventos naturales y antrópicos que han ocurrido a lo largo del final del Pleistoceno y el Holoceno. Concretamente, descubrimos que las poblaciones de esta especie han tenido una historia común hasta hace aproximadamente 100 mil años. A partir de este punto, empezaron a divergir las poblaciones de Asia y Europa y la especie entró en un declive continuado y generalizado, en el que las poblaciones más occidentales mantuvieron tamaños efectivos menores que las poblaciones orientales. Estos declives, y el aislamiento de las poblaciones que conllevaron, estuvieron detrás de la diferenciación genética que se observa a día de hoy entre poblaciones del centro de Europa que se encuentran física y ecológicamente muy próximas. Por el contrario, las poblaciones asiáticas son relativamente homogéneas, mostrando un patrón de aislamiento por distancia, a pesar de los hábitats tan diferentes que engloban. Nuestros resultados apuntan que tanto las divergencias mitogenéticas como nucleares podrían tener su origen en las fluctuaciones climáticas acaecidas durante el Pleistoceno, y en los impactos antropogénicos que se intensificaron progresivamente durante el Holoceno. A lo largo del capítulo 2 el análisis de una muestra de lince boreal residente en la península ibérica hace 2 mil años, junto con el reanálisis de fragmentos mitocondriales de muestras antiguas, aporta luz a los patrones biogeográficos de la especie en el pasado en el oeste de Europa. Específicamente, los resultados sugieren que la población, que entró en Iberia en el cambio del Pleistoceno al Holoceno y que vivió hasta su extinción en el siglo XX, formaba parte de un linaje próximo y posiblemente ancestral al que se encuentra hoy en Cárpatos y los países bálticos. Esta muestra presenta la diversidad más baja reportada hasta la fecha para lince boreal sugiriendo que la población sufría un empobrecimiento genético que pudo precipitar su extinción, seguramente debido a la combinación de una serie de eventos fundadores y una presión antrópica intensificada durante el Holoceno. Además, la distribución de haplotipos mitocondriales en el espacio y el tiempo apuntan a la coexistencia de distintos linajes, que pudieron convivir en Europa aunque con ciertas fluctuaciones en su distribución. Mientras que un linaje más relacionado con Balcanes y Cáucaso fue predominante en el Pleistoceno En el suroeste de Europa, otro linaje, relacionado con Europa central y Asia lo fue durante el Holoceno. En el capítulo 3 el uso de muestras antiguas, de 2 a 4 mil años de antigüedad nos permite caracterizar genéticamente la población que existió en la península ibérica en ese periodo, y los cambios que ha sufrido en su historia reciente. Específicamente, encontramos que esta población era relativamente homogénea y cercana a la población de Andújar y que tenía una diversidad genética más baja que las poblaciones actuales de la especie. El aumento de la diversidad con el tiempo ha sido concomitante con un proceso de flujo génico con lince boreal que se registra por igual en las dos poblaciones remanentes de lince ibérico. Esta señal de introgresión es mayor con linces boreales occidentales que con linces orientales, pero similar entre linces de distintas poblaciones occidentales. La muestra de lince boreal residente en la península ibérica hace dos mil años y analizada en el capítulo anterior, muestra, al contrario de lo esperado, menos alelos compartidos con lince ibérico que las poblaciones actuales de lince boreal, indicando que este linaje no estuvo implicado en este proceso de introgresión y que fue posiblemente otro linaje hibrido y ancestral de las poblaciones contemporáneas la fuente de la introgresión. Además, encontramos que este intercambio fue aumentando a lo largo del tiempo, de modo que las muestras más recientes, muestran un mayor número de alelos compartidos. Este intercambio, aunque seguramente está detrás del aumento de diversidad en la especie, pudo haber tenido consecuencias desconocidas en cuanto a eficacia biológica y demografía. En el capítulo 4 se comparan poblaciones que han sufrido un cuello de botella muy pronunciado, frente a otras que se han mantenido demográficamente más estables tanto de lince boreal como de ibérico, para investigar los patrones que dejan en el genoma los cuellos de botella. Encontramos que, como esperamos, la intensidad y/o duración del cuello de botella está negativamente correlacionada con la diversidad de las poblaciones. Las correlaciones, esperadas y conocidas, de la diversidad con numerosas variables se observan en las poblaciones no sometidas a cuello de botella intenso, pero son más débiles en poblaciones que han sufrido cuello de botella intenso. Además, zonas del genoma que se encuentran bajo selección natural, relacionadas con la estructura proteica pero también con la regulación, así como el cromosoma X, muestran una acumulación de alelos a baja frecuencia en las poblaciones que han sufrido un cuello de botella, de forma que incluso llegan a superar en diversidad a las poblaciones demográficamente más estables y grandes. Esta acumulación se concentra en zonas de alta mutación, en las que algunas variantes segregando a muy baja frecuencia aumentarían en frecuencia tras el cuello de botella hasta hacerse perceptibles, lo que parece estar relacionado con una relajación de la selección purificadora.Universidad Pablo de Olavide de Sevilla. Escuela de Doctorad

The cargo protein MAP17 (PDZK1IP1) regulates the cancer stem cell pool activating the Notch pathway by abducting NUMB

Purpose: Cancer stem cells (CSC) are self-renewing tumor cells, with the ability to generate diverse differentiated tumor cell subpopulations. They differ from normal stem cells in the deregulation of the mechanisms that normally control stem cell physiology. CSCs are the origin of metastasis and highly resistant to therapy. Therefore, the understanding of the CSC origin and deregulated pathways is important for tumor control. Experimental Design: We have included experiments in vitro, in cell lines and tumors of different origins. We have used patient-derived xenografts (PDX) and public transcriptomic databases of human tumors. Results: MAP17 (PDZKIP1), a small cargo protein overexpressed in tumors, interacts with NUMB through the PDZ-binding domain activating the Notch pathway, leading to an increase in stem cell factors and cancer-initiating–like cells. Identical behavior was mimicked by inhibiting NUMB. Conversely, MAP17 downregulation in a tumor cell line constitutively expressing this gene led to Notch pathway inactivation and a marked reduction of stemness. In PDX models, MAP17 levels directly correlated with tumorsphere formation capability. Finally, in human colon, breast, or lung there is a strong correlation of MAP17 expression with a signature of Notch and stem cell genes. Conclusions: MAP17 overexpression activates Notch pathway by sequestering NUMB. High levels of MAP17 correlated with tumorsphere formation and Notch and Stem gene transcription. Its direct modification causes direct alteration of tumorsphere number and Notch and Stem pathway transcription. This defines a new mechanism of Notch pathway activation and Stem cell pool increase that may be active in a large percentage of tumors.Ministerio de Economía y Competitividad PI15/00045, CTS-1848Junta de Andalucía PI-00-96-2014, PI-0306-201

Meta-analysis: associated factors for the adoption and disclosure of CSR practices in the banking sector

This document seeks to identify the associated factors that lead banking institutions to adopt and disclose CSR practices, considering that previous studies show contradictory results. Therefore, is important to integrate the findings from previous research, given the importance of CSR practices for the financial performance and the level of risk of organizations. The study employed the random effect meta-analysis technique, the data analysis was carried out with papers published between 2005 and 2021 and integrates the results of research that has analyzed a total of 6208 observations in 40 countries. The results of the research show a significant positive association between, legitimacy of existence and reputation as associated factors for developing CSR practices, whereas the regulation, the inclusion of foreign board members, and stakeholder relationships have an insignificant positive association as an associated factor with the development of CSR practices. Corporate governance factors have a significant positive relationship with the presence of women on the board and the size of the board. In addition, the board’s independence and the duality of the CEO have an insignificant negative association. This paper provides evidence of the need for research in CSR practices in the banking sector, especially in Latin America where the literature is almost non-existent. In addition, it also shows the need for research on corporate governance factors, especially on how the presence of women on the board influences the development of CSR practices, considering the scarce existing literature that analyses these factors

Nivel de eficiencia del uso de recursos por las organizaciones públicas. Caso: sistemas sanitarios españoles

Objectives: This paper seeks to detect, in the Spanish health system, which health services are efficient, and which are not, as well as propose corrective measures that allow inefficient health services to achieve efficiency. Methods: This paper applies the Data Envelopment Analysis (DEA) methodology, which allows obtaining natural and managerial efficiencies, as well as deviations from inefficient units in relation to efficient ones and proposing corrective measures that imply only budgetary (natural) modifications or changes in the policies of resource management (management). Results: Through the efficiencies, or the lack of them, the health services of the 17 Spanish autonomous communities are classified into four groups: With high, medium-high, medium-low or low natural or managerial efficiency. Conclusions: The lack of natural efficiency can be corrected with a greater budgetary endowment and the lack of managerial efficiency with a budget cut and changes in resource management policies. This tendency contrary to the adjustments is precisely what gives this work of interest and novelty with respect to others that apply the DEA in different sectors such as those that study the impact on the environment of resource consumption. Another important aspect of this study is the possibility of applying it to other countries with similar political structures.Objetivos: Con este trabajo se persigue detectar, en el sistema sanitario español, que servicios sanitarios son eficientes y cuáles no, así como proponer medidas correctoras que permitan a los servicios sanitarios ineficientes alcanzar la eficiencia. Metodología: Este trabajo aplica la metodología del análisis envolvente de datos (DEA), que permite obtener las eficiencias natural y gerencial, así como las desviaciones de las unidades ineficientes con relación a las eficientes, y proponer medidas correctoras que impliquen únicamente modificaciones presupuestarias (natural) o cambios en las políticas de gestión de recursos (gerencial). Resultados: A través de las eficiencias, o la falta de ellas, los servicios sanitarios de las 17 comunidades autónomas españolas se clasifican en cuatro grupos: Con eficiencia natural o gerencial alta, media-alta, media-baja o baja. Conclusiones: La falta de eficiencia natural puede corregirse con una mayor dotación presupuestaria, la falta de eficiencia gerencial con un recorte presupuestario y cambios en las políticas de gestión de recursos. Esta tendencia contraria de los ajustes es precisamente la que dota este trabajo del interés y novedad con respectos a otros que aplican el DEA en sectores diferentes como aquellos que estudian el impacto en el medioambiente de los consumos de recursos. Otro aspecto importante de este estudio es la posibilidad de aplicarlo a otros países con estructuras políticas similares

Effect of thickness on color and translucency of a multi-color polymer-infiltrated ceramic-network material

Objectives: To evaluate the effect of thickness on color and translucency of a multi-color polymer-infiltrated ceramic-network (PICN) material. Methods: Specimens of 0.5, 1.0, 1.5 mm thicknesses were obtained by sectioning VITA ENAMIC® multiColor (E-MC) High Translucent CAD-CAM blocks (1M1-HT, 1M2-HT, 2M2-HT, 3M2-HT, and 4M2-HT). Spectral reflectance and color coordinates were measured on white and black backgrounds using a spectroradiometer, CIE D65 illuminant and CIE 45 /0 geometry. CIEDE2000 color and translucency differences (ΔE00 and ΔTP00) between thicknesses and adjacent layers were evaluated using their respective 50:50% perceptibility and acceptability thresholds (PT00 and AT00). Results: In general, ΔE00 between thicknesses for all shades and layers were above AT00 in general. Chroma decreased from cervical to incisal layers with statistically significant differences (p < 0.05), and ΔE00 between sequential layers were above PT00, for all shades and thicknesses. TP00 decreased from 0.5 to 1.5 mm and increased from cervical to incisal layers for all shades with statically significant translucency differ- ences (p < 0.05). In general, for all thicknesses, TPT00 < ΔTP00 < TAT00 for sequential layers. Conclusions: The gradient in color and translucency of E-MC PICN material was influenced by the thickness of the CAD-CAM block. In addition, color and TP transi- tion values between the layers depends on the thickness and shade. Clinical significance: The effect of thickness must be taken into account by dental technicians and dentists when CAD-CAM multicolor PICN materials are used.University of Granada, Grant/Award Number: A.TEP.280.UGR18Spanish Ministry of Science, Innovation and Universities, Grant/ Award Number: PGC2018-101904-A-I00Government of Andalusia, Spain, Grant/Award Number: P20-0020

Does Backgrounds Color Influence the Appearance of Gingiva-Colored Resin-Based Composites?

This research was funded by the Spanish Ministry of Science, Innovation and Universities, grant number PGC2018-101904-A-100, the Government of Andalusia, grant number P20-00200, the University of Granada, grant number A.TEP.280.UGR18, and the APC was funded by the grant number PGC2018-101904-A-100.Dental materials are mainly tested in vitro, so laboratory conditions must reproduce the oral environment to ensure the validity of their results. This study aimed to evaluate the influence of backgrounds on the color of gingiva-colored resin-based composites (GCRBC). Three discs of each of 20 shades of GCRBCs and each thickness (1 and 2 mm) were prepared. Diffuse reflectance was measured on-air and over three natural teeth (0M3/B1, 3M3/B3, and 5M3/B4 shades of Vita 3D Master/Vita Classical guides, respectively) using a calibrated spectroradiometer, CIE D65 illuminant and the CIE 45 degrees/0 degrees geometry. CIEDE2000 color difference formula and its 50:50% perceptibility and acceptability thresholds have been used to calculate and interpret the results. It can be stated that the background influences the color of all GCRBCs tested, although the effect is more pronounced for 1 mm thick samples. L*, a* and b* coordinates values of GCRBCs on air were significantly different from those obtained on natural teeth backgrounds, and the total color differences were greater than the acceptability thresholds. Since GCRBCs are placed on a dental substrate in clinical conditions, it is not advisable to perform color measurements of GCRBCs on-air because of the high color differences found. This recommendation is especially relevant for thin specimens.Spanish Government PGC2018-101904-A-100Government of Andalusia P20-00200University of Granada A.TEP.280.UGR1

Color stability and degree of conversion of gingiva-colored resin-based composites

Objectives: To evaluate gingiva-colored resin-based composites' (GCRBC) color stability and degree of conversion (DC%). Methods: Eight discs (8 1 mm) of 20 shades of GCRBC were prepared. Color coordinates were measured against a gray background with a calibrated spectroradiometer, CIE D65 illuminant and the CIE 45 /0 geometry at baseline and after 30 days of storage in distilled water, coffee, and red wine. Color differences (ΔE00) between final and baseline conditions were calculated. An ATR-FTIR spectrometer with a diamond tip was used to calculate DC%. The results were analyzed statistically using ANOVA and Tukey post-hoc test. The level of significance was p < 0.05. Results: DC% and color stability correlated with each other and with the GCRBC brand. DC% ranged between 43% and 96%, highest values correspond to flowable composites. All composites have experienced color changes after immersion in water, wine and coffee. However, the magnitude of the color change has varied widely depending on the immersion medium and the GCRBC. Color changes generated by the wine were, globally, greater than those induced by coffee (p < 0.001) and above the acceptability thresholds. Conclusions: The DC% of GCRBCs is sufficient to achieve adequate biocompatibility and physicomechanical properties, but the high susceptibility to staining could compromise aesthetic long-term results. Clinical Significance: The degree of conversion and the color stability of gingivacolored resin-based composites correlated with each other. All composites have experienced color changes after immersion in water, wine and coffee. Color changes generated by wine were, globally, greater than those induced by coffee and above the acceptability thresholds that could compromise aesthetic long-term results.Junta de Andalucía, Grant/Award Number: P20-00200; Universidad de GranadaGrant/Award Number: CBU

Relevant optical properties for gingiva-colored resin-based composites

The authors acknowledge funding support from the Spanish Ministry of Science, Innovation and Universities (PGC2018-101904-A-100) and from the i+D+I Government of Andalusia 2020, Spain (P20-00200).Objectives: To evaluate the optical properties of gingiva-colored resin-based composites (GCRBCs). Methods: Five discs (8 mm diameter x 1mm height) of 17 shades of GCRBCs were prepared. Diffuse reflectance was measured against white and black backgrounds using a calibrated spectroradiometer, CIE D65 illuminant and the CIE 45⁰/0⁰ geometry. Relative translucency parameter was calculated using ΔE00 (RTP00). Translucency differences were evaluated using published data of 50:50% translucency perceptibility (TPT00) and acceptability (TAT00) thresholds. Scattering (S) and absorption (K) coefficients and transmittance (T%) were calculated using Kubelka–Munk’s equations. Data were statistically analyzed using Kruskal–Wallis, Mann–Whitney tests, and VAF coefficient. Results: The RTP00 values of the 17 evaluated shades ranged from 8.69 to 21.34. There were perceptible translucency differences (TPT00=0.62) between different shades of the same brand and between composites designated with the same shade of different brands. Spectral distributions of S, K and T were wavelength- dependent. Although the spectral behavior of the S and K coefficients and T% were similar for all the gingival composites evaluated, the values of these parameters presented statistically significant differences between shades, which would justify the differences found in the relative translucency parameter. Conclusions: The optical properties S, K and T% of GCRBCs were significantly different, resulting in perceptible translucency differences between the same shade of different commercial brands and between different shades of the same brand. Clinical significance: Translucency differences of gingiva-colored composites may significantly influence their masking ability affecting the clinician’s choice of restorative material.Spanish Ministry of Science, Innovation and Universities (PGC2018-101904-A-100)i+D+I Government of Andalusia 2020, Spain (P20-00200

Augmented Reality in Physical Therapy: Systematic Review and Meta-analysis

Background: Augmented reality (AR) is a rapidly expanding technology; it comprises the generation of new images from digital information in the real physical environment of a person, which simulates an environment where the artificial and real are mixed. The use of AR in physiotherapy has shown benefits in certain areas of patient health. However, these benefits have not been studied as a whole. Objective: This study aims to ascertain the current scientific evidence on AR therapy as a complement to physiotherapy and to determine the areas in which it has been used the most and which variables and methods have been most effective. Methods: A systematic review registered in PROSPERO (International Prospective Register of Systematic Reviews) was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta - Analyses) recommendations. The search was conducted from July to August 2021 in the PubMed, PEDro, Web of Science, Scopus, and Cochrane Library scientific databases using the keywords augmented reality, physiotherapy, physical therapy, exercise therapy, rehabilitation, physical medicine, fitness, and occupational therapy. The methodological quality was evaluated using the PEDro scale and the Scottish Intercollegiate Guidelines Network scale to determine the degree of recommendation The Cochrane Collaboration tool was used to evaluate the risk of bias. Results: In total, 11 articles were included in the systematic review. Of the 11 articles, 4 (36%) contributed information to the meta-analysis. Overall, 64% (7/11) obtained a good level of evidence, and most had a B degree of recommendation of evidence. A total of 308 participants were analyzed. Favorable results were found for the Berg Balance Scale (standardized mean change 0.473, 95% CI -0.0877 to 1.0338; z=1.65; P=.10) and the Timed Up and Go test (standardized mean change -1.211, 95% CI -3.2005 to 0.7768; z=1.194; P=.23). Conclusions: AR, in combination with conventional therapy, has been used for the treatment of balance and fall prevention in geriatrics, lower and upper limb functionality in stroke, pain in phantom pain syndrome, and turning in place in patients with Parkinson disease with freezing of gait. AR is effective for the improvement of balance; however, given the small size of the samples and the high heterogeneity of the studies, the results were not conclusive. Future studies using larger sample sizes and with greater homogeneity in terms of the devices used and the frequency and intensity of the interventions are needed