Beatriz Santamaria

TNF-related weak inducer of apoptosis (TWEAK) promotes kidney fibrosis and Ras-dependent proliferation of cultured renal fibroblast.

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) regulates apoptosis, proliferation and inflammation in renal epithelial cells and plays a role in acute kidney injury. However, there is little information on the chronic effects of TWEAK. We hypothesized that TWEAK may influence renal fibrosis and regulate kidney fibroblast biology, in part, through Ras pathway. We studied a chronic model of experimental unilateral ureteral obstruction in wild type and TWEAK deficient mice, and a murine model of systemic TWEAK overexpression. TWEAK actions were also explored in cultured renal and embryonic fibroblasts. TWEAK and TWEAK receptor expression was increased in the obstructed kidneys. The absence of TWEAK decreased early kidney tubular damage, inflammatory infiltrates and myofibroblast number. TWEAK deficient mice had decreased renal fibrosis 21days after obstruction, as assessed by extracellular matrix staining. In mice without prior underlying kidney disease, systemic overexpression of TWEAK induced kidney inflammation and fibrosis. In cultured fibroblasts, TWEAK induced proliferation through activation of the Ras/ERK pathway. TWEAK also activated nuclear factor κB (NFκB)-dependent inflammatory chemokine production in murine renal fibroblasts. In conclusion, lack of TWEAK reduces renal fibrosis in a model of persistent kidney insult and overexpression of TWEAK led to renal fibrosis. TWEAK actions on renal fibroblasts may contribute to the in vivo observations, as TWEAK promotes inflammatory activity and proliferation in fibroblast cultures.

Protein tyrosine phosphatase 1B modulates GSK3β/Nrf2 and IGFIR signaling pathways in acetaminophen-induced hepatotoxicity

Acute hepatic failure secondary to acetaminophen (APAP) poisoning is associated with high mortality. Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of tyrosine kinase growth factor signaling. In the liver, this pathway confers protection against injury. However, the involvement of PTP1B in the intracellular networks activated by APAP is unknown. We have assessed PTP1B expression in APAP-induced liver failure in humans and its role in the molecular mechanisms that regulate the balance between cell death and survival in human and mouse hepatocytes, as well as in a mouse model of APAP-induced hepatotoxicity. PTP1B expression was increased in human liver tissue removed during liver transplant from patients for APAP overdose. PTP1B was upregulated by APAP in primary human and mouse hepatocytes together with the activation of c-jun (NH2) terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK), resulting in cell death. Conversely, Akt phosphorylation and the antiapoptotic Bcl2 family members BclxL and Mcl1 were decreased. PTP1B deficiency in mouse protects hepatocytes against APAP-induced cell death, preventing glutathione depletion, reactive oxygen species (ROS) generation and activation of JNK and p38 MAPK. APAP-treated PTP1B−/− hepatocytes showed enhanced antioxidant defense through the glycogen synthase kinase 3 (GSK3)β/Src kinase family (SKF) axis, delaying tyrosine phosphorylation of the transcription factor nuclear factor-erythroid 2-related factor (Nrf2) and its nuclear exclusion, ubiquitination and degradation. Insulin-like growth factor-I receptor-mediated signaling decreased in APAP-treated wild-type hepatocytes, but was maintained in PTP1B−/− cells or in wild-type hepatocytes with reduced PTP1B levels by RNA interference. Likewise, both signaling cascades were modulated in mice, resulting in less severe APAP hepatotoxicity in PTP1B−/− mice. Our results demonstrated that PTP1B is a central player of the mechanisms triggered by APAP in hepatotoxicity, suggesting a novel therapeutic target against APAP-induced liver failure.

Insulin directly stimulates VEGF-A production in the glomerular podocyte.

Podocytes are critically important for maintaining the integrity of the glomerular filtration barrier and preventing albuminuria. Recently, it has become clear that to achieve this, they need to be insulin sensitive and produce an optimal amount of VEGF-A. In other tissues, insulin has been shown to regulate VEGF-A release, but this has not been previously examined in the podocyte. Using in vitro and in vivo approaches, in the present study, we now show that insulin regulates VEGF-A in the podocyte in both mice and humans via the insulin receptor (IR). Insulin directly increased VEGF-A mRNA levels and protein production in conditionally immortalized wild-type human and murine podocytes. Furthermore, when podocytes were rendered insulin resistant in vitro (using stable short hairpin RNA knockdown of the IR) or in vivo (using transgenic podocyte-specific IR knockout mice), podocyte VEGF-A production was impaired. Importantly, in vivo, this occurs before the development of any podocyte damage due to podocyte insulin resistance. Modulation of VEGF-A by insulin in the podocyte may be another important factor in the development of glomerular disease associated with conditions in which insulin signaling to the podocyte is deranged.

Essential role of Nrf2 in the protective effect of lipoic acid against lipoapoptosis in hepatocytes.

Excess of saturated free fatty acids, such as palmitic acid (PA), in hepatocytes has been implicated in nonalcoholic fatty liver disease. α-Lipoic acid (LA) is an antioxidant that protects against oxidative stress conditions. We have investigated the effects of LA in the early activation of oxidative and endoplasmic reticulum stress, lipid accumulation, and Nrf2-mediated antioxidant defenses in hepatocytes treated with PA or in rats fed a high-fat diet. In primary human hepatocytes, a lipotoxic concentration of PA triggered endoplasmic reticulum stress, induced the apoptotic transcription factor CHOP, and increased the percentage of apoptotic cells. Cotreatment with LA prevented these effects. Similar results were found in mouse hepatocytes in which LA attenuated PA-mediated activation of caspase 3 and reduced lipid accumulation by decreasing PA uptake and increasing fatty acid oxidation and lipophagy, thereby preventing lipoapoptosis. Moreover, LA augmented the proliferation capacity of hepatocytes after PA challenge. Antioxidant effects of LA ameliorated reactive oxygen species production and endoplasmic reticulum stress and protected against mitochondrial apoptosis in hepatocytes treated with PA. Cotreatment with PA and LA induced an early nuclear translocation of Nrf2 and activated antioxidant enzymes, whereas reduction of Nrf2 by siRNA abolished the benefit of LA on PA-induced lipoapoptosis. Importantly, posttreatment with LA reversed the established damage induced by PA in hepatocytes, as well as preventing obesity-induced oxidative stress and lipoapoptosis in rat liver. In conclusion, our work has revealed that in hepatocytes, Nrf2 is an essential early player in the rescue of oxidative stress by LA leading to protection against PA-mediated lipoapoptosis.

Resveratrol treatment restores peripheral insulin sensitivity in diabetic mice in a sirt1‐independent manner

SCOPE Mice with deletion of insulin receptor substrate (IRS) 2 develop hyperglycaemia, impaired hepatic insulin signaling and elevated gluconeogenesis. Protein tyrosine phosphatase 1B (PTP1B) inhibition by resveratrol improves peripheral insulin sensitivity of these mice. Although resveratrol activates Sirtuin1 (Sirt1), the mechanisms underlying its beneficial effects are not totally elucidated. In this study, we have investigated whether Sirt1 mediates the effects of resveratrol in controlling insulin resistance in diabetic mice. METHODS AND RESULTS We attempted to ameliorate peripheral insulin resistance in two diabetic models, Irs2-deficient (Irs2(-/-)) mice and streptozotocin (STZ)-injected mice by resveratrol treatment or Sirt1 overexpression. Resveratrol improved systemic insulin sensitivity of Irs2-deficient mice. Irs2-deficient mice are characterized by high levels of PTP1B expression in liver and muscle. Interestingly, resveratrol decreased PTP1B in both tissues, thereby restoring IRS1-mediated insulin signaling. Moreover, resveratrol also restored insulin sensitivity and hepatic insulin signaling in STZ-diabetic mice. In contrast, moderate overexpression of Sirt1 neither normalized PTP1B levels nor restored insulin signaling in Irs2-deficient mice or STZ-diabetic mice. CONCLUSION Resveratrol improves peripheral insulin signaling independently of Sirt1 in diabetic mice in association with the inhibition of PTP1B and, therefore, this polyphenol could be an effective adjuvant for the treatment of diabetes.

IRS2 and PTEN are key molecules in controlling insulin sensitivity in podocytes

Insulin signaling to the glomerular podocyte is important for normal kidney function and is implicated in the pathogenesis of diabetic nephropathy (DN). This study determined the role of the insulin receptor substrate 2 (IRS2) in this system. Conditionally immortalized murine podocytes were generated from wild-type (WT) and insulin receptor substrate 2-deficient mice (Irs2(-/-)). Insulin signaling, glucose transport, cellular motility and cytoskeleton rearrangement were then analyzed. Within the glomerulus IRS2 is enriched in the podocyte and is preferentially phosphorylated by insulin in comparison to IRS1. Irs2(-/-) podocytes are significantly insulin resistant in respect to AKT signaling, insulin-stimulated GLUT4-mediated glucose uptake, filamentous actin (F-actin) cytoskeleton remodeling and cell motility. Mechanistically, we discovered that Irs2 deficiency causes insulin resistance through up-regulation of the phosphatase and tensin homolog (PTEN). Importantly, suppressing PTEN in Irs2(-/-) podocytes rescued insulin sensitivity. In conclusion, this study has identified for the first time IRS2 as a critical molecule for sensitizing the podocyte to insulin actions through its ability to modulate PTEN expression. This finding reveals two potential molecular targets in the podocyte for modulating insulin sensitivity and treating DN.

Inhibition of T-cell activation by the CTLA4-Fc Abatacept is sufficient to ameliorate proteinuric kidney disease

Diabetic nephropathy (DN) remains an unmet medical challenge as its prevalence is projected to continue to increase and specific medicines for treatment remain undeveloped. Activation of the immune system, in particular T-cells, is emerging as a possible mechanism underlying DN disease progression in humans and animal models. We hypothesized that inhibition of T-cell activation will ameliorate DN. Interaction of B7-1 (CD80) on the surface of antigen presenting cells with its binding partners, CTLA4 (CD152) and CD28 on T-cells, is essential for T-cell activation. In this study we used the soluble CTLA4-Fc fusion protein Abatacept to block cell surface B7-1, preventing the cellular interaction and inhibiting T-cell activation. When Abatacept was dosed in an animal model of diabetes-induced albuminuria, it reduced albuminuria in both prevention and intervention modes. The number of T-cells infiltrating the kidneys of DN animals correlated with the degree of albuminuria, and treatment with Abatacept reduced the number of renal T-cells. As B7-1 induction has been recently proposed to underlie podocyte damage in DN, Abatacept could be efficacious in DN by protecting podocytes. However, this does not appear to be the case as B7-1 was not expressed in 1) kidneys of DN animals; 2) stimulated human podocytes in culture; or 3) glomeruli of DN patients. We conclude that Abatacept ameliorates DN by blocking systemic T-cell activation and not by interacting with podocytes.

Endogenous NAMPT dampens chemokine expression and apoptotic responses in stressed tubular cells

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease and identification of new therapeutic targets is needed. Nicotinamide phosphoribosyltransferase (NAMPT) is both an extracellular and intracellular protein. Circulating NAMPT is increased in diabetics and in chronic kidney disease patients. The role of NAMPT in renal cell biology is poorly understood. NAMPT mRNA and protein were increased in the kidneys of rats with streptozotocin-induced diabetes. Immunohistochemistry localized NAMPT to glomerular and tubular cells in diabetic rats. The inflammatory cytokine TNFα increased NAMPT mRNA, protein and NAD production in cultured kidney human tubular cells. Exogenous NAMPT increased the mRNA expression of chemokines MCP-1 and RANTES. The NAMPT enzymatic activity inhibitor FK866 prevented these effects. By contrast, FK866 boosted TNFα-induced expression of MCP-1 and RANTES mRNA and endogenous NAMPT targeting by siRNA also had a proinflammatory effect. Furthermore, FK866 promoted tubular cell apoptosis in an inflammatory milieu containing the cytokines TNFα/IFNγ. In an inflammatory environment FK866 promoted tubular cell expression of the lethal cytokine TRAIL. These data are consistent with a role of endogenous NAMPT activity as an adaptive, protective response to an inflammatory milieu that differs from the proinflammatory activity of exogenous NAMPT. Thus, disruption of endogenous NAMPT function in stressed cells promotes tubular cell death and chemokine expression. This information may be relevant for the design of novel therapeutic strategies in DN.

IRS2 is an essential molecule for insulin signalling in renal cells

6 pages, 4 figures, 17 references.-- Trabajo presentado al 7th International Workshop on Sap Flow, celebrado del 21-24 de octubre 2008, en Sevilla, Espana.This research has been supported in part by the “Ministerio de Ciencia y Tecnologia”, Spain, (VIN00-036-C6-3, RF02-004-C5-2, HP2000-0032, VIN03-002-C6-3). The Excma. Diputacion Provincial de Pontevedra also provided a research grant.Presentacion con 38 diapositivas ; Conferencia invitada ; ECLA 2016: Gas on the rock, CSIC, Madrid, Spain, 21-25 Nov. 2016El objetivo perseguido en este trabajo ha sido avanzar y profundizar en el conocimiento de la ruta de degradacion del acido fenilacetico (PA) en Escherichia coli W En primer lugar se ha caracterizado la segunda etapa en la degradacion de PA, la transformacion de PA en fenilacetil-CoA (PA-CoA). Se ha demostrado por una parte, que los genes paaABCDE son todos necesarios para la hidroxilacion del anillo aromatico de PA-CoA, primer intermediario de la ruta, y por otro lado, que esta hidroxilacion es dependiente de oxigeno. En segundo lugar se han estudiado el gen paaX, que codifica un represor que controla la expresion de los genes catabolicos. En este trabajo se ha confirmado que la proteina PaaX tambien esta implicada en la represion de su propia expresion, y se ha observado que el PA-CoA es el inductor del sistema. La proteina PaaX es capaz de competir y desplazar la union de la RNA polimerasa a la zona promotora. Se ha observado que los promotores de la ruta de degradacion del PA no se pueden activar en anaerobiosis, porque no puede sintetizarse PA-CoA, ya que la PA-CoA ligasa pierde rapidamente su actividad en ausencia de oxigeno. En tercer lugar se ha estudiado la funcion del gen paaY que se encuentra contiguo al gen paaX La ausencia del gen paaY retrasa de forma significativa el crecimiento de E. coli en PA pero solo cuando esta presente el represor PaaX. Ademas las celulas deficientes en este gen no son capaces de activar de forma efectiva la ruta paa cuando la bacteria utiliza unicamente PA como fuente de energia. La proteina PaaY se ha hiperexpresado y purificado, comprobandose que es una metaloenzima trimerica que presenta actividad tioesterasa sobre algunos compuestos derivados de CoA.8 paginas.-- 3 figuras.-- 1 tabla.-- 23 referencias.-- Comunicacion oral presentada en Geothermal biology and geochemistry in Yellowstone National Park: Proceeding of the Thermal Biology Institute workshop, Yellowstone National Park, WY, October 2003This paper was made possible thanks to the sponsorship of the Spanish Ministry of Science and Technology (Research Project BHA2003-04414-C03-01).Recientemente se ha sintetizado en nuestro laboratorio el primer oxido mixto de cobre y plata. Tal sintesis ha sido posible gracias a la utilizacion de metodos de quimica suave y baja temperatura, que impiden que los oxidos de plata se descompongan. En este trabajo se describe el estudio llevado a cabo sobre el comportamiento electroquimico del oxido mixto de cobre y plata, Ag2Cu2O3 ,mediante voltametria ciclica y electrolisis tanto para los procesos de oxidacion como de reduccion. Dicho compuesto sufre varios procesos redox cuando es reducido, obteniendose plata metalica y cobre metalico como productos finales, sin que se de regeneracion del oxido al volver a oxidar a estos. En cambio al ser oxidado el Ag2Cu2O3, se observa la formacion de una fase oxidada de estequiometria Ag2Cu2O4�}� a partir de la cual se puede regenerar el compuesto original.Con el desarrollo de la biologia molecular, la produccion de proteinas en sistemas heterologos ha cobrado gran importancia en el campo de la biotecnologia. La posibilidad de purificar e inmovilizar estas proteinas recombinantes representan una ventaja importante para su aplicacion en procesos industriales o en el desarrollo de productos biotecnologicos. Por ello, el uso de polipeptidos de afinidad, mas conocidos como tags, que proporcionan caracteristicas determinadas a las proteinas de fusion es una tecnologia ampliamente utilizada tanto en investigacion basica como en procesos industriales. En esta Tesis se ha trabajado con dos sistemas muy ventajosos que permiten purificar e inmovilizar proteinas de fusion en soportes solidos utilizando dos tipos de tags: - El ChBD, tag de afinidad que reconoce colina y otros compuestos analogos, permiten purificar en un unico paso de cromatografico utilizando un soporte muy economico, la DEAE-celulosa. Ademas ofrece la posibilidad de inmovilizar dichas proteinas en papel de DEAE-celulosa manteniendo su funcionalidad. - BioF, un nuevo tag disenado en esta Tesis, que permite obtener proteinas de fusion inmovilizadas en granulos de polihidroxialcanoato de cadena media, un soporte solido biodegradable y biocompatible conocido como bioplastico. Las proteinas de fusion asociadas a estos granulos pueden purificarse con ellos mediante una sencilla centrifugacion y, si es necesario, liberarse en solucion mediante tratamientos suaves. En esta Memoria se han determinado distintas caracteristicas de dichos tags se han disenado las herramientas biotecnologicas necesarias para su utilizacion. Ademas se han realizado proteinas de fusion que demuestran la funcionalidad de ambos tags. Entre las proteinas obtenidas, es relevante destacar, por su interes industrial, la DAO-ChBD, con actividad D-aminoacido oxidasa y la ChBD-Pyr, con actividad pirofosfatasa. Tambien seIn Possibilistic Decision Theory (PDT), decisions are ranked by a pressimistic or by an optimistic qualitative criteria. The preference relations induced by these criteria have been axiomatized by corresponding sets of rationality postulates, both a la von Neumann and Morgenstern and a la Savage. In this paper we first address a particular issue regarding the axiomatic systems of PDT a la von Neumann and Morgenstern. Namely, we show how to adapt the axiomatic systems for the pessimistic and optimistic criteria when some finiteness assumptions in the original model are dropped. Second, we show that a recent axiomatic approach by Giang and Shenoy using binary utilities can be captured by preference relations defined as lexicographic refinements of the above two criteria. We also provide an axiomatic characterization of these lexicographic refinements.The southwestern margin of the Iberian Peninsula hosts the present-day convergent boundary between the European and African Plates. Plate convergence is about 4 mm/yr and is accommodated over a wide and diffuse deformation zone (Sartori et al. 1994) characterized by significant and widespread seismic activity (e.g. Grimison & Chen 1986; Buforn et al. 1995; Stich et al. 2005), being the source of the largest events in Western Europe, such as the 1755 Lisbon Earthquake and Tsunami (estimated Moment Magnitude Mw 8.5) (Abe 1989; Johnston 1996; Baptista et al. 1998) and 1969 Horseshoe Earthquake (Mw 7.8) (Fukao 1973; Stich et al. 2005) (Fig. 1).Application of Isotopic analysis in archaeometallurgy research Isotopic analysis of archaeological metals plays a key role in provenance and trade/exchange studies. These analytical techniques were developed originally in the field of Earth Sciences for the study of rocks and minerals, but since the 60s of the XX century have also been used for the analysis of many ancient materials (metals, glass and glazed pottery). Of particular interest for tracing the provenance of metals is lead (Pb). Depending on age, type and geochemical composition of the ore source, different isotopic compositions are found. Due to isotopic ratios not changing through the metallurgical processes (smelting and melting), the isotopic fingerprint of one metal can be linked with the ore sources. Recent investigations with Cu, Sn and Os isotopes provide new paths for the study of the metals provenance.Financial support of the DGES (Project PB97-1046) and DGI (Project BOS2000-0296-C03-01) of Spain is kindly acknowledged.Trabajo presentado por Yolanda Aguilera Gutierrez para optar al grado de Doctor y que ha sido realizado en el Departamento de Quimica Agricola de la Facultad de Ciencias de la UAM.En esta Tesis Doctoral se caracterizan las dos proteinas MFP1 (MAR-blinding Filament-like Protein 1) nucleares de Allum cepa mediante inmunodeteccion e inmunoprecipitacion con dos sueros desarrollados contra las proteinas de tomate y Arabidopsis. AcMFP1-78KDa es una proteina constitutiva con un pl ligeramente acido (5,5), y se distribuye en distintos subdominios nucleares en funcion del tipo celular y el tejido. Mediante microscopia electronica se ha demostrado que lo hace en pequenos dominios localizados preferentemente en la periferia de las masas de heterocromatina densa. Posee ademas una doble localizacion subcelular, localizados en los cloroplastos con un patron de distribucion similar al de MFP1 en otras especies. El segundo homologo, de 90 Kda y al basico (8,5-9,5), posee distintos estados de fosforilacion que influyen en su union a la matriz nuclear, habiendose demostrado que la Caseina kinasa CK2 endogena puede regular dicha union. AcMFP1-90KDa se acumula en cuerpos nucleares cuyo numero se incrementa por la proliferacion celular y la presencia de luz. Tambien se distribuye por el reticulo de la matriz nuclear, asociada a los filamentos del nucleoesqueleto. Estudios de co-localizacion demuestran que las proteinas AcMFP1 no forman parte de los complejos de replicacion, los de procesamiento co-transcripcional, los granulos intercromatinicos ni los Cuerpos de Cajal. Las distintas caracteristicas y patrones de distribucion y expresion de ambas proteinas sugieren funciones diferentes, o al menos distintas formas de regulacion. Los resultados sugieren una interaccion de AcMFP1-78KDa con la eucromatina, y una funcion estructural en la matriz nuclear para AcMFP1-90KDa.6 pages, 5 figures, 18 references. Electronic Newsletter. CSIC Thematic Network on Cultural Heritage and Network on Science and Technology for the Conservation of Cultural Heritage Instituto de Recursos Naturales y Agrobiologia de Sevilla, CSIC, Apartado de Correos 1052, 41080 Sevilla (Spain)This paper deals with three main aspects os the imagery of youth in Hellenistic Iberia. First, I study the iconography of vegetation and flowers associated with juvenile vigour and with the gods, as expressed in vase scenes from San Miguel de Liria or La Alcudia de Elche. Second, I analyze the ideal of the young leader or prince, spread in Iberia by the Barcids and especially by Hannibal and, later, by the Roman conquerors, exemplified by Publius Cornelius Scipio). I point to the function fulfilled by the youth in political pacts, via amicitia and fides. Literary and numismatic sources, emphasizing the Carthago Nova mint, are also studied. Finally, I refer to the representation of a duel by youths, as in the case of the sculptured monument at Osuna (Seville), and put forward the hypothesis of a ritualization of war in festivals, in which young men and women take part, although I leave this last part open to further debate.espanolSe estudio el efecto de la contaminacion con altas cantidades de un residuo compuesto de isomeros de 1,2,3,4,5,6-hexaclorociclohexano (HCHs) (10, 50 y 100 g HCHs kg-1 suelo) sobre la densidad en el suelo de microorganismos heterotrofos, algas y cianobacterias fijadoras de N2 , sobre algunos microorganismos implicados en los ciclos de C y N (amonificantes, amiloliticos, y celuloliticos) asi como sobre la capacidad de las comunidades microbianas edaficas para degradar varios sustratos carbonados (perfiles fisiologicos de las comunidades microbianas, CCLP). Estas propiedades microbianas se analizaron a las 2 semanas y los 2 y 4 meses de la aplicacion del contaminante. Tambien se estudio el efecto de la contaminacion con HCHs aplicado a distintas concentraciones y en forma de particulas de distinto tamano, sobre la respiracion del suelo. A corto plazo tras la adicion del contaminante al suelo, la densidad de los microorganismos heterotrofos aumento, la abundancia de algas descendio y la poblacion de cianobacterias no vario significativamente. A los 4 meses de la contaminacion el efecto de las concentraciones de contaminante mas altas (50 y 100 g HCHs kg-1 suelo) sobre los grupos microbianos mencionados fue negativo. El residuo de HCHs tuvo un efecto sobre la poblacion amonificante similar a la observada en los microorganismos heterotrofos. Las densidades de amiloliticos y celuloliticos no se vieron afectadas o aumentaron, a corto plazo despues de la adicion de contaminante, aunque, a largo plazo (4 meses tras la contaminacion) experimentaron una reduccion con las concentraciones mas altas de HCHs. A los dos meses de la contaminacion, la capacidad de las comunidades microbianas del suelo para degradar sustratos carbonados (CCLP) se vio negativamente afectada por el residuo de HCHs. Cabe resaltar el descenso en la degradacion de aminoacidos, que fue especialmente importante en los suelos con 50 y 100 g HCHs kg-1 suelo. El residuo de HCHs tambien afecto a la respiracion del suelo, aunque el efecto dependio de la cantidad y tamano de particula del contaminante y de la presencia o ausencia de microorganismos procedentes de un emplazamiento contaminado con HCHs por largo tiempo (adaptados a la contaminacion con HCHs). Cuando estuvieron presentes microorganismos adaptados a HCHs y el contaminante se aplico en forma de particulas 4-10 mm, la respiracion del suelo se vio estimulada con concentraciones entre 20 y 100 g HCHs kg-1 suelo e inhibida con concentraciones mayores de 200 g HCHs kg-1 suelo. Al aplicar el residuo de HCHs en forma de particulas EnglishThe effect of heavy contamination with a residue composed of 1,2,3,4,5,6-hexachlorocyclohexane isomers (HCHs) (10, 50 and 100 g HCHs kg-1 soil) on the densities of cultivable soil heterotrophs, algae and N2 -fixing cyanobacteria, on soil microorganisms involved in the N and C cycles (ammonifiers, amylolytics and cellulolytics) as well as on the ability of soil microbial communities to degrade several C substrates (community level physiological profiles, CCLP) was studied. These microbial properties were analysed 2 weeks, and 2 and 4 months, after the soil was artificially contaminated. The effect of HCHs residue applied at different concentrations, and in the form of particles of different sizes on soil respiration was studied. The influence of the presence or absence of microorganisms from a long term polluted site on the effect of HCHs on soil respiration was also analysed. In the short term after the addition of the contaminant to the soil, the density of heterotrophs increased, the abundance of algae decreased, while the population of cyanobacteria did not change significantly. Four months after contamination the effect of the highest concentrations of HCHs (50 and 100 g HCHs kg-1 soil) on these microbial groups was negative. The HCH residue had a similar effect on the ammonifying population to that on heterotrophs. The densities of amylolytics and cellulolytics were either not modified, or were stimulated by the contaminant in the short term but, in the longer term (4 months after the contamination), were inhibited by HCHs applied at the highest concentrations. Two months after contamination, the ability of soil microbial communities to degrade C substrates (CCLP) was negatively affected by HCHs. It was noteworthy the decrease in the ability for degrading aminoacids, which was particularly important in the soils with 50 and 100 g HCHs kg-1 soil. HCHs also affected soil respiration but the effect depended on the HCH concentration, particle size of the contaminant, and on the presence or absence of microorganisms from a long term HCH-contaminated site (adapted to HCH contamination). When microorganisms adapted to HCH contamination were present and the contaminant was applied in form of particles of 4-10 mm, the soil respiration was stimulated by HCH at concentrations between 20 and 100 g HCH kg-1 and inhibited with concentrations higher than 200 g HCH kg-1 soil. If the HCHs were applied as particlesThis study was supported by the Spanish Ministry of Science and Technology (grant BOS2000-0450).Este trabajo pretende una reflexion sobre la verdadera dimension cientifica de Jose Maria Esquerdo. A la luz de las escasas fuentes disponibles, se lleva a cabo un analisis critico de sus aportaciones a la teoria y a la clinica �que vienen a completar otros acercamientos previos centrados en aspectos politicos, profesionales y asistenciales�. Se hace hincapie en la vertiente mas doctrinal de su pensamiento, ubicando el mismo en el marco del alienismo espanol y europeo de su epoca y valorando hasta que punto la obra de esta figura de la medicina espanola decimononica pueden ser considerada, tal y como se ha sostenido con frecuencia, relevante en el contexto en que fue realizadaIn this paper, we propose a box particle filtering algorithm for state estimation in nonlinear systems whose model assumes two types of uncertainties: stochastic noise in the measurements and bounded errors affecting the system dynamics. These assumptions respond to situations frequently encountered in practice. The proposed method includes a new way to weight the box particles as well as a new resampling procedure based on repartitioning the box enclosing the updated state. The proposed box particle filtering algorithm is applied in a fault detection schema illustrated by a sensor network target tracking example.Tesis doctoral inedita. Universidad Autonoma de Madrid, Facultad de Ciencias, Departamento de Geologia y Geoquimica. Fecha de lectura: 22-04-0811 pages, 4 figures, 1 table, 75 references. We thank the Consejeria de Medio Ambiente, Junta de Andalucia, and the Direction of the National Park of Sierra Nevada for permission to field work, constant support and facilities. We are also especially grateful to Empresa de Transformacion Agraria S.A. (TRAGSA) for carrying out the experimental reforestation. We thank Sergio de Haro and several students for field assistance. David Nesbitt looked over the English version of the manuscript.En este trabajo se ha estudiado la sintesis de hidroxiapatito por el metodo de combustion. Se ha considerado la influencia de los parametros de temperatura, tiempo de reaccion, relacion Ca/P y la acidez del medio, para sintetizar particulas nanometricas de hidroxiapatito por un metodo rapido y simple como es el de combustion. Se han empleado como materias primas nitrato de calcio y fosfato amonico, y como combustible urea. Las diferentes sintesis se han llevado a cabo en una mufla y los polvos obtenidos han sido caracterizados por DRX, FESEM, ATD-TG, FTIR y superficie especifica.En este trabajo se presentan y discuten los resultados de la caracterizacion arqueometrica realizada sobre un conjunto representativo de figurillas ceramicas del Clasico Tardio procedentes de las excavaciones arqueologicas efectuadas en la ciudad maya de Calakmul (Campeche, Mexico). Los objetivos principales han sido recabar informacion sobre la tecnologia de manufactura de estas ceramicas y evaluar su posible procedencia. La caracterizacion arqueometrica se ha llevado a cabo mediante las siguientes tecnicas complementarias: microscopia optica convencional (MO), difraccion de rayos X (DRX) de polvo, espectroscopia infrarroja por Transformada de Fourier (FT- R) y fluorescencia de rayos X (FRX). Con el fin de aislar grupos ceramicos con un perfil quimico similar, los datos obtenidos con FRX se han analizado tambien con tecnicas exploratorias de analisis estadistico multivariante. Los resultados indican que la mayoria de las figurillas se manufacturaron localmente con una materia prima arcillosa rica en carbonato de calcio (calcita). Tambien se ha identificado un pequeno grupo de ceramicas rico en carbonatos mixtos de calcio y magnesio (dolomita), que podria ser foraneo o procedente de otra zona de la region de Calakmul. Estos datos sugieren que la produccion de figurillas ceramicas pudo estar asociada a talleres ligados al monopolio sobre la produccion ceramica que el poder centralizado de la ciudad de Calakmul ejercio en este periodo.Se ha estudiado la influencia del humo de silice sobre el mecanismo de hidratacion del monoaluminato de calcio (CaAl2O4) a temperatura ambiente y con una relacion agua/solidos de 0,5. La evolucion de las fases hidratadas, que se forman en los primeros instantes de la reaccion, se ha estudiado por difraccion de rayos X de laboratorio con una resolucion temporal de 36 min. La integracion de picos de difraccion seleccionados de las fases: Ca2Al2O5·8H2O (Ca2Al2(OH)10·3H2O), CaAl2O4 y Ca4Al2(OH)12(CO3)·5H2O, ha permitido establecer la cinetica de la reaccion. Asi, se ha puesto de manifiesto que el humo de silice provoca una drastica disminucion en el periodo de induccion de la hidratacion y acelera la formacion de los hidratos cristalinos metaestables Ca2Al2(OH)10·3H2O y Ca4Al2(OH)12(CO3)·5H2O. Estos resultados se han confirmado por Termogravimetria, Analisis Termico Diferencial y Microscopia Electronica de Barrido. El mecanismo de hidratacion propuesto se apoya en datos previos de Resonancia Magnetica Nuclear de Solidos (RMN) de 29Si de los autores de este articulo.Una version anterior de este trabajo fue presentada en el XIX Congreso de Geografos Espanoles: ‘Espacios publicos, espacios privados’, organizado por la AGE y el Departamento de Geografia, Urbanismo y Ordenacion del Territorio de la Universidad de Cantabria. Santander (Espana), Octubre 2005.Trabajo realizado en el marco del proyecto de investigacion BHA2003-01664 del MCYT y como contratado por el Programa Ramon y Cajal del Ministerio de Ciencia y Tecnologia (convocatoria 2002)The aim of the present work is to determine the physical and hydrodynamic properties of the soils and the factors that govern the spatial and temporal variability of soil moisture in the semiarid sector of the Duero basin (Spain). To accomplish this, we used a soil moisture-measuring network, with 20 stations, each endowed with 4 TDR (Time Domain Reflectometry) probes inserted at different depths. At each of the soil moisture sampling points we determined the texture, bulk density, organic matter content and the water retention curve. The study period lasted 21 months, during which contrasted climatic situations were recorded. The results show that the textural fraction is the main variable accounting for the patterns of spatial soil moisture distribution over time. Its effect is direct on i) the water retention capacity of the soils, with an amount of plant available water ranging between 6.5 and 8.9 % vol.; ii) the spatial variability of the soil moisture throughout the area, and iii) soil moisture distribution along the profile. Finally, an outstanding aspect is the considerable effect of the organic matter, despite its low contents, on the water retention capacity of the soils studied.El trabajo experimental presentado en esta memoria por Roberto Alonso Gil, ha sido realizado en el Instituto de Biologia y Genetica Molecular (Universidad de Valladolid-CSIC) y en el Instituto de Investigaciones Biomedicas “Alberto Sols” (Universidad Autonoma de Madrid-CSIC; Facultad de Ciencias, Departamento de Biologia Molecular), bajo la direccion del Dr. Manuel Izquierdo Pastor.Two new sterols, 1-2, unus ually hydroxylated at C -21 have been isolated from the marine pulmonate Trimusculus peruvianus. Compound 2 possesses a Δ 7 -3α,5α,6β-triol nucleus unprecedented in marine organisms. The structure and stereochemistries were determined on the basis of spectral studies, particularly NMR and MS spectroscopic data. 1 and 2 are the entire sterol content of the mollusk and both exhibit moderate in vitro cytotoxic activity against human colon carcinoma cell lines.4 paginas, 4 figuras, 4 tablas.-- Trabajo presentado a la 34a Sesion Cientifica, Bilbao 2003.In Drosophila, mutations in double-strand DNA break (DSB) repair enzymes, such as spn-B, activate a meiotic checkpoint leading to dorsal-ventral patterning defects in the egg and an abnormal appearance of the oocyte nucleus. Mutations in spn-D cause an array of ovarian phenotypes similar to spn-B. We have cloned the spn-D locus and found that it encodes a protein of 271 amino acids that shows significant homology to the human RAD51C protein. In mammals the spn-B and spn-D homologs, XRCC3 and RAD51C, play a role in genomic stability in somatic cells. To test for a similar role for spn-B and spn-D in double-strand DNA repair in mitotic cells, we analyzed the sensitivity of single and double mutants to DSBs induced by exposure to X rays and MMS. We found that neither singly mutant nor doubly mutant animals were significantly sensitized to MMS or X rays. These results suggest that spn-B and spn-D act in meiotic recombination but not in repair of DSBs in somatic cells. As there is no apparent ortholog of the meiosis-specific DMC1 gene in the Drosophila genome, and given their meiosis-specific requirement, we suggest that spn-B and spn-D may have a function comparable to DMC1.Este trabajo se realizo en el marco del proyecto BTE 2002-040 17 -C02-01 del Ministerio de Ciencia y Tecnologia en el desarrollo de la beca FPI con referencia BES- 2003-1573.Trabajo realizado en el marco del Programa Contrato Ramon y Cajal (2002) y financiado por los proyectos de Investigacion: BHA-2002-00588 y BHA 2003-01664 del Ministerio de Ciencia y Tecnologia.Trabajo realizado en el marco del Proyecto BHA 2002-00588 (Ministerio de Ciencia y Tecnologia- Espana)espanolUna caracteristica esencial de la vida de todo organismo es la adaptacion constante a los cambios que tienen lugar en su entorno. Para ello, esas variaciones ambientales deben ser leidas y traducidas en respuesta fisiologica. De ahi que, los organismos hayan desarrollado diversos mecanismos de integracion, de amplificacion y de mantenimiento de la senal del medio. La naturaleza de los mecanismos de senalizacion y respuesta celular varia en funcion de la complejidad del organismo. Sin embargo, se puede decir que el aspecto basico de toda adaptacion es de caracter universal, en el que se pueden distinguir tres grandes etapas: 1) la lectura de la senal propiciada por el entorno, 2) la transmision de la senal recibida y, 3), la respuesta celular. Al final toda respuesta celular implica un cambio intracelular basado en el control de la expresion genica y/o actividad de proteinas, cuya funcion permite adecuar el metabolismo celular a las necesidades de cada momento. La tesis aqui presentada se centra en el mecanismo de senalizacion por glucosa. La glucosa es la principal fuente de carbono y de energia para la mayoria de los organismos. Ademas de ser nutriente se puede considerar a la glucosa como una hormona de crecimiento, ya que regula varios aspectos del crecimiento, metabolismo y desarrollo celular. Para llevar a cabo dicho estudio hicimos uso de la levadura Saccharomyces cerevisiae. En S. cerevisiae la presencia de glucosa modula distintos procesos celulares. La regulacion del metabolismo supone controlar las rutas implicadas a distintos niveles: a corto plazo se modifica la actividad de distintas proteinas, como es el caso de la inactivacion por catabolito de los transportadores de galactosa y maltosa; mientras que a largo plazo se producen cambios en la actividad transcripcional. La glucosa en S. cerevisiae regula la expresion genica mediante dos rutas diferentes denominadas ruta de induccion y ruta de represion. Mediante la ruta de represion se inactiva la expresion genica de un gran numero de genes tales como los genes responsables de la utilizacion de otras fuentes de carbono distintas a la glucosa, de la gluconeogenesis y la respiracion. Por el contrario, mediante la ruta de induccion se activan los genes responsables de la utilizacion de la glucosa, tales como genes que codifican para enzimas glicoliticos y transportadores de glucosa, HXTs. Para estudiar la senalizacion por glucosa estudiamos la regulacion de la expresion genica del transportador de glucosa de baja afinidad, HXT1, de S. cerevisiae, cuyo sistema de expresion se considera modelo de induccion genica por glucosa. Los resultados obtenidos demuestran que la regulacion por glucosa de la expresion del transportador de glucosa de baja afinidad, HXT1, de S. cerevisiae se realiza a traves de al menos tres mecanismos de senalizacion diferentes: el sistema de induccion genica por glucosa, la ruta TOR, ruta de senalizacion de nutrientes a traves de los homologos a las proteinas 14-3-3, y la ruta HOG, ruta de respuesta a estres osmotico. La accion coordinada de dichos mecanismos modula la actividad transcripcional sobre el gen HXT1, permitiendo finalmente que el gen se exprese ante la presencia de glucosa. Por tanto, la regulacion de HXT1 es un ejemplo mas de como se interrelacionan distintos procesos celulares para adecuar el metabolismo celular segun las necesidades. TOR (target of rapamycin). HOG ( High osmolarity glycerol signal transduction pathway ). __________________________________________________________________________________________________ EnglishSensing nutrients is a fundamental requisite for all living cells. For most eukaryotic cells glucose is a major source of energy, having significant and varied effects on cell function. Maintaining glucose homoeostasis is consequently of great importance to many organisms. Interest in identifying mechanisms by which cells sense and respond to variations in glucose concentration has increased lately. Glucose regulates genes in all cells by mechanisms which have been conserved throughout evolution. The consensus is that glucose could act on target cells either by binding to a receptor at the cell surface, or through its metabolism. The aim of this thesis is to elucidate the mechanism involved in glucose sensing in the yeast Saccharomyces cerevisiae. Yeast cells prefer glucose as carbon source and have evolved mechanisms for sensing and responding to wildly fluctuating levels of extracellular glucose. These mechanisms involve a large family of hexose transporters (HXT proteins) and the glucose transporter homologues Snf3 and Rgt2. Snf3 and Rgt2 are glucose-sensing proteins at the plasma membrane with no detectable transport activity. They sense the extracellular glucose and generate an intracellular glucose signal that triggers the induction of HXT gene expression. Expression of HXT1, a gene encoding a Saccharomyces cerevisiae low-affinity glucose transporter, is regulated by glucose availability, being activated in the presence of glucose and inhibited when the levels of the sugar are scarce. In this study we show how glucose regulate HXT1 expression, and how glucose requires at least the coordinated action of three different mechanisms of signalling: glucose signalling pathway, osmotic stress signalling (HOG pathway) and nutrient-signalling (TOR pathway) .9 pages, 3 figures, 2 tables, 55 references. We thank the Consejeria de Medio Ambiente, Junta de Andalucia, for permitting our fieldwork in the Sierra Nevada National Park and Sierra de Baza Natural Park. We are especially grateful to Sergio de Haro, Elena Baraza and Jose Antonio Hodar for their help in the field. Peter Klinkhamer and two anonymous reviewers provided helpful comments on earlier versions of the manuscript. David Nesbitt improved the English version.The Spanish Ministry of Science and Technology (Project REN2003-00381) and the Spanish Ministry of Environment (Project RESEL).Resumen del poster presentado al 48th European Association for the Study of Diabetes (EASD) Annual Meeting, celebrado en Berlin (Alemania) del 1 al 5 de octubre de 2012.-- et al.2 paginas y 1 tabla.- Resumen del poster presentado en el IV Congreso de Mejora genetica de plantas, celebrado en Cordoba entre el 14 y el 16 de octubre de 2008.Understanding the processes of tree population recruitment and their limitations, is the scientific basis to assure the forest natural regeneration, and to improve techniques of restoration and afforestation. We present here preliminary results of a collaborative project (HETEROMED). The environmental heterogeneity of Mediterranean forests was related to natural patterns of seedling establishment. Factorial design experiments of seed addition were carried out and the resulting emergence and survival were related to the conditions of light and soil moisture. The fieldwork was carried out at two natural areas in South Spain: Sierra Nevada National Park (higher mountains on the Southeast) and Los Alcornocales Natural Park (lower mountains in Sierra del Aljibe range, on the southern tip of the Iberian Peninsula). The experiments were focussed in seven target species - Quercus suber, Quercus canariensis, Quercus ilex, Quercus pyrenaica, Pinus sylvestris, Acer granatense and Sorbus aria. In addition, a glasshouse factorial experiment investigated the differential response of the four Quercus species to the combined effects of shade and drought. In both field sites (Sierra Nevada and Sierra del Aljibe) seedling emergence differed among species, but was not significantly affected by habitat (light availability). In Sierra Nevada, seedling survival after dry summer was statistically different between tree species, habitat type and irrigation treatment. Summer drought was the main cause of seedling mortality. Survival was higher in deep shade habitats than in open stands. Irrigation boosted survival in open areas (full light) and under shrublands (medium shade), but had scant effect inside woodland stands (deep shade). In Sierra del Aljibe, there were significant differences in seedling survival of Quercus suber between habitat types. Most surviving seedlings after the dry summer were in habitats with medium shade (under tree canopy), rather than in full light (open areas) or deep shade (closed forest) habitats. In the glasshouse study, the seedling mass (after six months of growth) was statistically different between species, and between light and water treatments. In the deep shade treatment seedling mass was not affected by stopping irrigation (simulating seasonal drought), unlike in the full light. A comparison of field and glasshouse results is carried out. A conflict between components of regeneration (seedling emergence, survival, and growth) is demonstrated as common in Mediterranean forests. The implications for ecological restoration are discussed and future perspectives of HETEROMED project are advanced.Presentacion con 40 diapositivas; Theoretical Challenges in Small Molecule Dynamics; The 15th ICQC Satellite Meeting, Dalian, China, 2-6 June 2015; http://www.sklmr.dicp.ac.cn/2015icqc/Financiacion del Ministerio de Ciencia y Tecnologia a traves de los proyectos MAT2000-1495 y MAT2000-1533-C03-02.Los fondos para la realizacion de los estudios que componen la presente memoria fueron proporcionados por el Ministerio de Educacion que concedio una beca de formacion de personal investigador al licenciado Rodrigo Manuel Megia Palma (BES-2010-038427).8 paginas, 3 figuras, 20 referencias.-- 5th International Symposium on Olive Growing, celebrado en Izmir, Turquia, 2004.Los estudios realizados en esta Tesis han permitido la identificacion y caracterizacion del potencial catabolico de Azoarcus sp. CIB, capaz de degradar anaerobicamente (condiciones desnitrificantes) compuestos aromaticos tales corno tolueno y m-xileno. Por primera vez en el genero Azoarcus se ha propuesto una ruta central de degradacion anaerobica de compuestos aromaticos via benzoil-CoA y se han identificado los genes responsables de dicha ruta bioquimica, que se agrupan en un cluster, denominado bzd, organizado en un operon regulador, constituido por el gen bzdR, bajo el control del promotor PR y otro operon catabolico, bzdNOPQMSTUVWXYZ, bajo el control del promotor PN. Se ha disenado una casete portadora de los genes bzd en un vector movilizable de amplio espectro de huesped con el objetivo de explorar el potencial de la ingenieria de rutas anaerobicas, siendo esta la primera casete que se describe en el catabolismo anaerobico de compuestos aromaticos. El gen bzdA codifica una benzoato-CoA ligasa involucrada en la primera reaccion del catabolismo anaerobico de benzoato y reconoce corno sustratos una mayor variedad de compuestos aromaticos que otras benzoato-CoA ligasas descritas hasta el momento, por lo que su hiperproduccion en huespedes heterologos muestra interes biotecnologico para la sintesis de derivados de benzoil-CoA. La proteina reguladora BzdR constituye el primer represor transcripcional que se describe en el catabolismo anaerobico de compuestos aromaticos. Este regulador transcripcional interacciona con tres regiones operadoras presentes en el promotor catabolico PN inhibiendo su actividad, habiendose caracterizado, tambien por primera vez en catabolismo anaerobico de compuestos aromaticos, la naturaleza de la molecula inductora, el benzoil-CoA. La novedosa estructura modular de la proteina BzdR, constituida por un dominio de tipo HTH-XRE tipico de proteinas de union a ADN yEste trabajo ha sido realizado en el marco del Programa Ramon y Cajal del MCyT (Convocatoria 2002).Se pretende estimar el efecto de un eventual cambio climatico y edafico sobre el patron de almacenamiento de carbohidratos en plantulas de un ano de tres especies lenosas mediterraneas del genero Quercus. Para ello se han cultivado las plantulas bajo tres condiciones contrastadas de fertilidad y tres de riego, experimento no factorial, durante una estacion de crecimiento. Se espera que en los medios menos fertiles se acumule carbono en forma de reservas debido a la limitacion en el crecimiento por falta de nutrientes. Asimismo, en condiciones de riego bajo, aumente la concentracion de glucosa para contribuir al ajuste osmotico de las hojas. Por ultimo, esperamos que Q. faginea, la especie de crecimiento mas rapido, invierta mayor cantidad de carbono en crecimiento y por tanto acumule menos almidon. Las concentracion de almidon en raiz y tallo de Q. ilex y Q. coccifera fue inversamente proporcional al nivel de fertilizacion. La concentracion de glucosa foliar mostro mayores concentraciones en las plantulas que experimentaron deficit hidrico. La especie que mas carbohidratos almaceno fue Q. faginea. Nuestro estudio sugiere, que el efecto de un incremento de aridez sobre el almacenamiento de carbohidratos depende, no solo de la especie, sino tambien de la fertilidad del suelo sobre el que se asiente.Trabajo presentado en el V Simposio Nacional sobre Control de la Degradacion y uso Sostenible del Suelo, celebrado en Murcia (Espana), del 27 al 30 de junio de 2011Ministerio de Medio Ambiente (Proyecto RESEL) y Ministerio de Ciencia y Tecnologia (Proyecto REN2003-00381).Thesis submitted to the University of Castilla La Mancha by Silvia Diaz Fernandez in fulfilment of the requirements for the degree of Doctor of Philosophy.El presente trabajo comprende el diseno y procesamiento por colaje de suspensiones de sistemas multicapa basados en capas gruesas de alumina y capas finas de alumina-circona. Durante el enfriamiento desde la temperatura de sinterizacion se generan tensiones residuales en las capas debido a la expansion asociada a la transformacion martensitica de la circona. En esta investigacion se estudian los parametros de procesamiento para la fabricacion de estos sistemas laminados y se caracterizan microestructuralmente las capas que lo componen. Como resultado se obtienen multicapas ceramicas con diferente relacion de espesores entre capas adyacentes utilizando como metodo de control las cineticas de colaje de los correspondientes monoliticos. Adicionalmente, se determinan analiticamente las tensiones residuales generadas en los laminados por medio de las diferencias volumetricas determinadas en ensayos dilatometricos y del modulo elastico de cada capa. Se encuentra que en las capas delgadas se desarrollan elevadas tensiones de compresion mientras que en las gruesas se inducen tensiones residuales de traccion. El efecto de estas tensiones sobre la integridad mecanica del material se discute en terminos de las observaciones de fenomenos de fisuracion intrinseca: tanto de grietas de borde o ?edge cracks? en la superficie libre de las capas delgadas como de fisuras tunel o ?tunneling cracks? en las capas gruesas.Trabajo presentado en II EMBO Workshop on Cortical Interneurons in Health and Disease, celebrado en Costa d’en Blanes, Mallorca (Espana), del 24 al 27 de junio de 2012CBR systems solve problems by assessing their similarity with already solved problems (cases). Explanation of a CBR system prediction usually consists of showing the user the set of cases that are most similar to the current problem. Examining those retrieved cases the user can then assess whether the prediction is sensible. Using the notion of symbolic similarity, our proposal is to show the user a symbolic description that makes explicit what the new problem has in common with the retrieved cases. Specifically, we use the notion of anti-unification (least general generalization) to build symbolic similarity descriptions. We present an explanation scheme using anti-unification for CBR systems applied to classification tasks. This scheme focuses on symbolically describing what is shared between the current problem and the retrieved cases that belong to dierent classes. Examining these descriptions of symbolic similarities the user can assess which aspects are determining that a problem is classified one way or another. The paper exemplifies this proposal with an implemented application of the symbolic similarity scheme to the domain of predicting the carcinogenic activity of chemical compounds.Reseda sect. Glaucoreseda is a monophyletic group composed of five endemic tetraploid species with a disjunct distribution in the high mountains and plateaus of the Iberian Peninsula and Morocco. It was previously suggested that range shifts induced by Quaternary glaciations played an important role in the speciation of the group. We studied the evolution of R. sect. Glaucoreseda in order to infer historical range dynamics and speciation processes, and to understand current distributional patterns. Phylogeographic analyses were performed using nuclear ribosomal ITS and plastid trnL-F and rps16 sequences. Cloning of additive ITS sequences was carried out to elucidate the origin of intra-individual polymorphisms. A dated phylogeny based on ITS and cpDNA (rbcL, matK, trnL-F) sequences was used to estimate divergence times of R. sect. Glaucoreseda. Time estimates using Penalized Likelihood analyses indicate a late Pleistocene diversification of R. sect. Glaucoreseda. Incomplete lineage sorting of ancestral polymorphisms due to recent divergence, rather than rampant hybridisation, is suggested as the main cause of the phylogenetic incongruence detected between nuclear and plastid datasets. Our results support the vicariance hypothesis for population disjunctions in the Iberian Peninsula, in which an ancestral, widespread species could have undergone differentiation by Quaternary interglacial fragmentation. In contrast, long-distance dispersal across the Strait of Gibraltar may have been involved in the colonisation of North African plateaus by R. battandieri.La informacion cuantitativa sobre la radiacion disponible en el sotobosque es crucial para la comprension de multitud de aspectos relacionados con la ecologia y dinamica del bosque. Dado que la gestion del bosque es en buena medida la gestion de la luz, la combinacion de estudios sobre ecofisiologia, heterogeneidad luminica, dinamica forestal y cambio global representa un punto de encuentro entre la ecologia y la gestion forestal, algo muy necesario en ecosistemas mediterraneos donde las incertidumbres son grandes y las predicciones poco optimistas. En este trabajo se presentan resultados sobre la heterogeneidad temporal y espacial de la luz en el sotobosque de diversas formaciones forestales ibericas (encinares, alcornocales, pinares, abedulares y hayedos). En general se observa que las formaciones mediterraneas tiene una mayor estructura espacial y una mayor heterogeneidad luminica que los bosques no mediterraneos, que la radiacion disponible bajo un dosel es inversamente proporcional a la tolerancia a la sombra de las especies arboreas que lo componen y que el numero de destellos de sol disminuye con la radiacion total que llega al sotobosque (i.e. los destellos se hacen largos e intensos). Las implicaciones de estos resultados se interpretan considerando la informacion disponible sobre las respuestas de las plantas a la combinacion de sombra y sequia, y sobre el papel de la heterogeneidad abiotica en la coexistencia de especies. Se propone que el cambio global conduce a un sotobosque mas oscuro y luminicamente homogeneo, lo cual unido al incremento de aridez ira dando lugar a bosques huecos, pobres en especies y con escasa capacidad de regeneracion natural.The Tufted(1) (Tft(1)) dominant mutation promotes the generation of ectopic bristles (macrochaetae) in the dorsal mesothorax of Drosophila. Here we show that Tft(1) corresponds to a gain-of-function allele of the proneural gene amos that is associated with a chromosomal aberration at 36F-37A. This causes ectopic expression of amos in large domains of the lateral-dorsal embryonic ectoderm, which results in supernumerary neurons of the PNS, and in the notum region of the third instar imaginal wing, which gives rise to the mesothoracic extra bristles. Revertants of Tft(1), which lack ectopic neurons and bristles, do not show ectopic expression of amos. One revertant is a loss-of-function allele of amos and has a recessive phenotype in the embryonic PNS. Our results suggest that both normal and ectopic Tft(1) bristles are generated following similar rules, and both are subjected to Notch-mediated lateral inhibition. The ability of Tft(1) bristles to appear close together may be due to amos having a stronger proneural capacity than that of other proneural genes like asense and scute. This ability might be related to the wild-type function of amos in promoting development of large clusters of closely spaced olfactory sensilla.Web tematica.-- Proposito: divulgativo.-- Estado del proyecto: finalizado.-- Fecha de la consulta: 2019-01-10.-- Los materiales contenidos en esta pagina web estan protegidos por el Texto Refundido de la Ley de Propiedad Intelectual y legislacion conexa.Poster presentado a las II Jornadas del Grupo de Viticultura y Enologia (SECH), celebradas en Madrid el 3 y 4 de noviembre de 2016.