Geomorphological setting and main technological features of new Middle and Upper Pleistocene sites in the Lower Manzanares River Valley (Madrid, Spain)

Las intervenciones arqueológicas llevadas a cabo durante los años 1996 en Tafesa, 2005 en el yacimiento Hospital 12 de Octubre y 2006 en la desembocadura del arroyo Butarque (Villaverde-Barrio de Butarque) situados al sur de la ciudad de Madrid (España), han aportado nuevos conjuntos líticos contextualizados estratigráficamente en los depósitos fluviales pleistocenos correspondientes al tramo inferior del valle del río Manzanares. Los yacimientos arqueológicos analizados se sitúan geomorfológicamente en la denominada “Terraza Compleja del Manzanares” (TCMZ), la cual constituye un nivel fluvial engrosado (20-15 m de potencia) situado entre +22-16 m sobre el cauce actual del río, a lo largo de su margen derecha. Este nivel fluvial ha sido tradicionalmente considerado de edad Pleistoceno medio en base a la industria achelense y complejos faunísticos encontrados en sus niveles inferiores. Ciertamente, Tafesa es un yacimiento situado en la parte inferior-media de la terraza de +22 m con industria achelense y fauna de Pleistoceno medio. Por el contrario, los niveles superiores de esta misma terraza en los sectores del 12 de Octubre y Villaverde-Butarque se encuentran asociados a industrias del Paleolítico inferior y medio ya pertenecientes al Pleistoceno superior, como sugieren el conjunto de dataciones OSL y TL existentes para la zona. Los datos analizados en este trabajo indican que el desarrollo de este nivel de terraza engrosado comienza durante la parte final de Pleistoceno medio y abarca todo el Estadio Isotópico OIS 5, ya dentro del Pleistoceno superiorThe archaeological works developed during the years 1996 in the site of Tafesa, 2005 in the 12 de Octubre Metro Station site and 2006 in the confluence of the Butarque Stream (Villaverde-Barrio de Butarque site) located south of the Madrid City (Spain), have provided new lithic assemblages. These assemblages have been stratigraphically contextualized in the Pleistocene deposits of the Lower Manzanares river valley within the so-called “Manzanares Complex Terrace” (TCMZ). This fluvial terrace constitutes an anomalous thickened (20-15m) deposit at +22-16m above the present river thalweg mainly developed along the right (southern) valley margin. This fluvial level has been traditionally considered of middle Pleistocene age on the basis of the acheulian lithics and faunal assemblages typically located within its lower stratigraphic layers. Certainly, the Tafesa is a fluvial terrace site at +22 m with acheulian industry and middle Pleistocene faunal remains at its lower sedimentary sequence. However, the upper sedimentary levels of this same terrace in the 12 de Octubre y Villaverde-Butarque sites throw lithic assemblages of the lower and upper Paleolithic belonging to upper Pleistocene, as suggested by the available set of TL and OSL dates for the zone. The analyses developed in this study indicate that the development of this thickened fluvial terrace started during the end of the middle Pleistocene, but also comprise the whole Oxygen Isotopic Stage OIS 5 during the upper Pleistocene

ABCA1 Deficiency Affects Basal Cognitive Deficits and Dendritic Density in Mice

Producción CientíficaATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-free apolipoproteins and regulates the generation of high density lipoproteins. Previously, we have shown that lack of Abca1 significantly increases amyloid deposition and cognitive deficits in Alzheimer’s disease model mice expressing human amyloid-β protein precursor (APP). The goal of this study was to determine if ABCA1 plays a role in memory deficits caused by amyloid-β (Aβ) oligomers and examine neurite architecture of pyramidal hippocampal neurons. Our results confirm previous findings that Abca1 deficiency significantly impairs spatial memory acquisition and retention in the Morris water maze and long-term memory in novel object recognition of APP transgenic mice at a stage of early amyloid pathology. Neither test demonstrated a significant difference between Abca1ko and wild-type (WT) mice. We also examined the effect of intra-hippocampal infused Aβ oligomers on cognitive performance of Abca1ko mice, compared to control infusion of scrambled Aβ peptide. Age-matched WT mice undergoing the same infusions were also used as controls. In this model system, we found a statistically significant difference between WT and Abca1ko mice infused with scrambled Aβ, suggesting that Abca1ko mice are vulnerable to the effect of mild stresses. Moreover, examination of neurite architecture in the hippocampi revealed a significant decrease in neurite length, number of neurite segments, and branches in Abca1ko mice when compared to WT mice. We conclude that mice lacking ABCA1 have basal cognitive deficits that prevent them from coping with additional stressors, which is in part due to impairment of neurite morphology in the hippocampus

DEVELOPMENT AND EVALUATION OF THE ATOS SPONTANEOUS SPEECH CONVERSATIONAL SYSTEM

ABSTRACT In this paper we report our recent development work in Spanish spontaneous speech conversational systems. We describe the Automatic Telephone Operator Service (ATOS) and present the improvements introduced into it to deal with spontaneous speech, which are: (a) a task independent dialogue manager, that can be adapted to a new semantic domain by changing a configuration file. It also generates a prediction about the user's expected utterance to constrain the language model used by the speech recognizer. (b) a language modeling strategy, which allows to adapt the statistical language model to a new task with just few hundreds of sentences. This strategy reduces a 27% the word error rate. We also report the results, conclusions and the speech database collected in the evaluation of the ATOS system, which has been tested by 30 real users

Geoarqueología y paleontología de los depósitos de Pleistoceno Superior del antiguo Arroyo Abroñigal (Cuenca de Manzanares, Madrid): el yacimiento de Puente de los Tres Ojos

La excavación arqueológica del yacimiento del Puente de los Tres Ojos, próximo a la calle Cerro Negro (Madrid), ha aportado nuevos datos para profundizar en el conocimiento de la ocupación humana y en la reconstrucción paleoambiental del valle del antiguo arroyo Abroñigal, cuyo curso fluvial funcionó como afluente del río Manzanares posiblemente desde antes del Pleistoceno Superior hasta la segunda mitad del siglo XX. En el presente artículo se incluyen los aspectos geomorfológicos y cronoestratigráficos de los niveles excavados, documentándose varias secuencias fluviales y aluviales de relleno de la margen derecha del fondo de valle del Abroñigal en su tramo inferior. Durante la excavación se registró un amplio conjunto lítico, formado en su mayoría por piezas recuperadas en niveles de arenas y gravas correspondientes a episodios fluviales de media energía, a las que hay que añadir un porcentaje menor localizado en niveles de limos arcillosos y arenas finas. La mayor parte del conjunto lítico responde a sistemas técnicos propios del Paleolítico Medio, aunque destaca la presencia testimonial de piezas del Paleolítico Superior, además de restos de fauna de mamíferos correspondientes al Pleistoceno Superior, todo ello en niveles datados por OSL entre 14.400 y 11.170 años BP aproximadament

Opposing effects ofApoe/Apoa1double deletion on amyloid-β pathology and cognitive performance in APP mice

Producción CientíficaATP binding cassette transporter A1 (encoded by ABCA1) regulates cholesterol efflux from cells to apolipoproteins A-I and E (ApoA-I and APOE; encoded by APOA1 and APOE, respectively) and the generation of high density lipoproteins. In Abca1 knockout mice (Abca1(ko)), high density lipoproteins and ApoA-I are virtually lacking, and total APOE and APOE-containing lipoproteins in brain substantially decreased. As the ε4 allele of APOE is the major genetic risk factor for late-onset Alzheimer's disease, ABCA1 role as a modifier of APOE lipidation is of significance for this disease. Reportedly, Abca1 deficiency in mice expressing human APP accelerates amyloid deposition and behaviour deficits. We used APP/PS1dE9 mice crossed to Apoe and Apoa1 knockout mice to generate Apoe/Apoa1 double-knockout mice. We hypothesized that Apoe/Apoa1 double-knockout mice would mimic the phenotype of APP/Abca1(ko) mice in regards to amyloid plaques and cognitive deficits. Amyloid pathology, peripheral lipoprotein metabolism, cognitive deficits and dendritic morphology of Apoe/Apoa1 double-knockout mice were compared to APP/Abca1(ko), APP/PS1dE9, and single Apoa1 and Apoe knockouts. Contrary to our prediction, the results demonstrate that double deletion of Apoe and Apoa1 ameliorated the amyloid pathology, including amyloid plaques and soluble amyloid. In double knockout mice we show that (125)I-amyloid-β microinjected into the central nervous system cleared at a rate twice faster compared to Abca1 knockout mice. We tested the effect of Apoe, Apoa1 or Abca1 deficiency on spreading of exogenous amyloid-β seeds injected into the brain of young pre-depositing APP mice. The results show that lack of Abca1 augments dissemination of exogenous amyloid significantly more than the lack of Apoe. In the periphery, Apoe/Apoa1 double-knockout mice exhibited substantial atherosclerosis and very high levels of low density lipoproteins compared to APP/PS1dE9 and APP/Abca1(ko). Plasma level of amyloid-β42 measured at several time points for each mouse was significantly higher in Apoe/Apoa1 double-knockout then in APP/Abca1(ko) mice. This result demonstrates that mice with the lowest level of plasma lipoproteins, APP/Abca1(ko), have the lowest level of peripheral amyloid-β. Unexpectedly, and independent of amyloid pathology, the deletion of both apolipoproteins worsened behaviour deficits of double knockout mice and their performance was undistinguishable from those of Abca1 knockout mice. Finally we observed that the dendritic complexity in the CA1 region of hippocampus but not in CA2 is significantly impaired by Apoe/Apoa1 double deletion as well as by lack of ABCA1. In conclusion: (i) plasma lipoproteins may affect amyloid-β clearance from the brain by the 'peripheral sink' mechanism; and (ii) deficiency of brain APOE-containing lipoproteins is of significance for dendritic complexity and cognition

Intrathoracic solitary fibrous tumor - an international multicenter study on clinical outcome and novel circulating biomarkers

Intrathoracic solitary fibrous tumor (SFT) is a rare disease. Radical resection is the standard of care. However, estimating prognosis and planning follow-up and treatment strategies remains challenging. Data were retrospectively collected by five international centers to explore outcome and biomarkers for predicting event-free-survival (EFS). 125 histological proven SFT patients (74 female; 59.2%; 104 benign; 83.2%) were analyzed. The one-, three-, five- and ten-year EFS after curative-intent surgery was 98%, 90%, 77% and 67%, respectively. Patients age (>/=59 vs. 10 cm vs. 5 vs. < 5 HR 3.91, CI 1.40-10.89, p = 0.009) were prognostic after univariate analyses. After multivariate analyses tumor-dignity and fibrinogen remained as independent prognosticators. Besides validating the role of age, tumor-dignity, tumor-size, stage and resection margins, we identified for the first time inflammatory markers as prognosticators in SFT

Morfología foliar y estomática y transpiración cuticular en clones de eucalipto

El objetivo de este trabajo fue evaluar aspectos de la morfología foliar relacionados con el consumo de agua en clones de Eucalyptus procedentes de programas de mejora genética. Se utilizaron cinco clones de E. globulus y cuatro clones de híbridos de diversas especies de Eucalyptus. Se cultivaron en vivero al exterior, en contenedores. En 4 épocas del año, coincidentes con las 4 estaciones y en hojas desarrolladas durante cada estación, se evaluó la tasa de transpiración cuticular (Ec), el contenido hídrico relativo (CHRc) y el contenido de humedad en el momento del cierre estomático (Hc), el área foliar específica (SLA) y el tamaño y densidad de los estomas. Se obtuvieron diferencias significativas entre clones y entre fechas de medición. Los rangos de valores obtenidos fueron: densidad de estomas = 171 a 546 mm-2; SLA = 7.3 a 20.4 m2 kg–1; Hc = 51 a 71 %; Ec = 0.07 a 0.59 mmol m-2 s-1. Ello indica que no solo hay variabilidad genética en dichos parámetros sino que los individuos modifican sus parámetros morfo-fisiológicos durante el año para acomodarse a las condiciones ambientales

Contexto geomorfológico y principales rasgos tecnológicos de nuevos yacimientos del Pleistoceno Medio y Superior en el Valle Inferior del Manzanares (Madrid, España)

The archaeological works developed during the years 1996 in the site of Tafesa, 2005 in the 12 de Octubre Metro Station site and 2006 in the confluence of the Butarque Stream (Villaverde-Barrio de Butarque site) located south of the Madrid City (Spain), have provided new lithic assemblages. These assemblages have been stratigraphically contextualized in the Pleistocene deposits of the Lower Manzanares river valley within the so-called “Manzanares Complex Terrace” (TCMZ). This fluvial terrace constitutes an anomalous thickened (20-15m) deposit at +22-16m above the present river thalweg mainly developed along the right (southern) valley margin. This fluvial level has been traditionally considered of middle Pleistocene age on the basis of the acheulian lithics and faunal assemblages typically located within its lower stratigraphic layers. Certainly, the Tafesa is a fluvial terrace site at +22 m with acheulian industry and middle Pleistocene faunal remains at its lower sedimentary sequence. However, the upper sedimentary levels of this same terrace in the 12 de Octubre y Villaverde-Butarque sites throw lithic assemblages of the lower and upper Paleolithic belonging to upper Pleistocene, as suggested by the available set of TL and OSL dates for the zone. The analyses developed in this study indicate that the development of this thickened fluvial terrace started during the end of the middle Pleistocene, but also comprise the whole Oxygen Isotopic Stage OIS 5 during the upper Pleistocene.Las intervenciones arqueológicas llevadas a cabo durante los años 1996 en Tafesa, 2005 en el yacimiento Hospital 12 de Octubre y 2006 en la desembocadura del arroyo Butarque (Villaverde-Barrio de Butarque) situados al sur de la ciudad de Madrid (España), han aportado nuevos conjuntos líticos contextualizados estratigráficamente en los depósitos fluviales pleistocenos correspondientes al tramo inferior del valle del río Manzanares. Los yacimientos arqueológicos analizados se sitúan geomorfológicamente en la denominada “Terraza Compleja del Manzanares” (TCMZ), la cual constituye un nivel fluvial engrosado (20-15 m de potencia) situado entre +22-16 m sobre el cauce actual del río, a lo largo de su margen derecha. Este nivel fluvial ha sido tradicionalmente considerado de edad Pleistoceno medio en base a la industria achelense y complejos faunísticos encontrados en sus niveles inferiores. Ciertamente, Tafesa es un yacimiento situado en la parte inferior-media de la terraza de +22 m con industria achelense y fauna de Pleistoceno medio. Por el contrario, los niveles superiores de esta misma terraza en los sectores del 12 de Octubre y Villaverde-Butarque se encuentran asociados a industrias del Paleolítico inferior y medio ya pertenecientes al Pleistoceno superior, como sugieren el conjunto de dataciones OSL y TL existentes para la zona. Los datos analizados en este trabajo indican que el desarrollo de este nivel de terraza engrosado comienza durante la parte final de Pleistoceno medio y abarca todo el Estadio Isotópico OIS 5, ya dentro del Pleistoceno superior

Quaternary fossil horses within the Prados-Guatén Depression (Pantoja de La Sagra, Toledo)

Durante la primera reunión de campo del Grupo Madrileño de Cuaternario (GQM-AEQUA) se localizaron restos fragmentarios de dentición de caballos fósiles en los antiguos areneros de Pantoja de La Sagra (Toledo), actualmente en proceso de desmantelamiento y relleno. Ante la posibilidad de deterioro y pérdida los restos fueron recolectados y trasladados al Museo Nacional de Ciencias Naturales (CSIC, Madrid) donde se ha procedido a su análisis. Las piezas fósiles analizadas responden a un maxilar izquierdo con tres piezas dentales in situ (molares y premolares), y otras siete más aisladas. Todos los dientes aislados, junto con el fragmento de maxilar existente, corresponden a un adulto joven. Los restos fósiles se encontraban asociados a un nivel de arenas fluviales situado unos cuatro metros por debajo de la superficie de la Terraza de +15 m de la Depresión Prados-Guatén definida como un nivel perteneciente al tránsito Pleistoceno inferior-medio, del antiguo Sistema fluvial Manzanares-Guatén por Silva (1988). En concreto los niveles superiores de esta terraza han sido interpretados como resultado de la superposición de los últimos depósitos del antiguo sistema fluvial y los primeros asociados al relleno de la Depresión por tributarios de área fuente más local tras su abandono como consecuencia del proceso de captura del valle inferior del Manzanares por parte del Río Jarama al SW de la Ciudad de Madrid (Silva et al., 1988). Los caracteres morfológicos y morfométricos de las piezas dentarias permiten identificarlos como Equus ferus cf. mosbachensis cuya distribución bioestratigráfica abarca la parte final del Pleistoceno Medio (c.a. 500-200 ka B.P.). Junto a los restos fósiles aparecieron también escasos fragmentos líticos correspondientes a productos de lascado en sílex de difícil atribución tecnológica. Los restos fósiles analizados, indican que el depósito extensivo de arenas fluviales en el eje de la Depresión, culminó durante el final del Pleistoceno medio, y que la dinámica fluvial de la Depresión tras su proceso de abandono fue de hecho más activa de lo que se pensaba con la instalación de sistemas de arroyos relevantes alimentados por cabeceras locales antes del encajamiento definitivo actual de los arroyos Prados y Guatén.During the first field-meeting of the Madrid Quaternary Research Group (GQM-AEQUA) several fossil teeth remnants of horses were localised at the ancient sand-quarries of Pantoja de La Sagra (Toledo), which presently are abandoned and refilling in progress. The possibility of deterioration and loss of the localised fossils remnants induced by the quarry works, they were collected and taken away to the Museo Nacional de Ciencias Naturales (CSIC, Madrid) for their preservation and analysis. Fossil remains correspond to a left maxilla with two in situ molars, another one inset on its alveolar cavity, fragments of premolar cavities, as well as other seven more isolated teeth. These fossils were outcropping in a sandy level at four meters below the +15 m fluvial terrace surface of the axial sector of de Prados-Guatén Depression, which is considered the last fluvial level belonging to the ancient Manzanares-Guatén fluvial system during the Lower-Middle Pleistocene transit (Silva, 1988). In detail, the upper fluvial sediments of this particular terrace level were interpreted as the result of the overlapping between the last materials deposited by the ancient Manzanares-Guatén fluvial system and the first ones resulting from the readjustment of former tributaries after the abandonment of the Depression caused by fluvial capture of the Lower Manzanares Valley SW Madrid City. The morphological features of the oclusal surface of the horse teeth and morphometric comparative analyses indicate that they belong to the specie Equus ferus, and probably to the subspecie mosbachensis. However due to the bad definition of this group in Europe and the few individuals analysed the better classification is Equus ferus cf. mosbachensis. The bioestratigraphic distribution of this fossil horse group in Europe extends on the upper part of the Middle Pleistocene (c.a. 500-200 ka B.P.). Few lithic artefacts outcropped also associated to the fossil remains, constituted by laminar flakes of hard technological classification. Fossil remains analysed in this work joint to the unique previous quaternary fossil mammal described for the Prados-Guatén Depression constituted by Mammuthus meridionalis NESTI of the former quarry of Esquivias adjacent to the AVE railway line (Silva et al., 1988b; 1999). The chronostratigraphic attribution of the fossil horses (Upper Middle Pleistocene) described here indicate that fluvial sedimentary activity within the Depression was relevant after its abandonment. Ancient tributaries of the former Manzanares-Guatén fluvial system, feed by local-intrabasinal headwaters, reworked the previous sandy sediments triggering multiepisodic deposition during the upper part of the Middle Pleistocene, before the more recent eventual incision of present streams dissecting the Depression

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability