Biocronología de la Terraza Compleja de Butarque del río Manzanares en el Estanque de Tormentas al sur de Madrid (España)

Due to the construction of the Stormwater Tank in Villaverde (Madrid), two new Pleistocene vertebrate bearing sites were discovered within the sediments of the Complex Terrace of Butarque (TCB, in Spanish), called H-02 and H-03. Termoluminiscence (TL) dates placed the first site at the Late Pleistocene, more precisely at the end of the MIS 5. An older age within the Middle Pleistocene was obtained for H-03 (Domínguez-Alonso et al., 2009). In this work, we evaluate the agreement between the TL dates and the estimated ages resulting from the biochronological interpretation of the fossil mammal assemblages recovered in both sites. Whereas for H-03 there is consistency between the TL dating and the age estimated based on biocronological criteria, this is not the case for H-02. At this site, the presence of Microtus brecciensis points to an older age than the proposal based on TL, within the Middle Pleistocene. On the other hand, comparison of some biometric features between the H-02 and Áridos 1 populations of the last species allows to establish a younger age for the first site with regard to the second one. Taking into account the available dates for Áridos 1, which placed this site at the end of the MIS 11 (Panera et al., 2011), the age of H-02 must therefore be included in the last quarter of the Middle Pleistocene. In summary, TL dates for the H-02 site and, perhaps, some others obtained for the Stormwater Tank in Villaverde, seem to be minimum estimations of the age of the sediments, and do not represent their real age.Con motivo de la construcción en 2006 del Estanque de Tormentas en Villaverde (Madrid) se localizaron dos nuevos yacimientos de vertebrados del Pleistoceno, denominados H-02 y H-03, en depósitos de la Terraza Compleja de Butarque (TCB). Las dataciones realizadas por Termoluminiscencia (TL) situaron al primero de los yacimientos H-02 en el Pleistoceno Superior, al final del MIS 5, mientras que para el yacimiento H-03 se obtuvo una edad más antigua, ya dentro del Pleistoceno Medio (Domínguez-Alonso et al., 2009). En este trabajo se evalúa la concordancia de estas dataciones con la estimación de la edad obtenida a partir de la interpretación biocronológica de las asociaciones de mamíferos fósiles recuperadas en cada uno de los yacimientos. Mientras que para el yacimiento H-03 existe congruencia entre la datación por TL y la estimación de su edad a partir de criterios biocronológicos, que combinadas sitúan al yacimiento en la segunda mitad del Pleistoceno Medio, no ocurre lo mismo en el caso de H-02. En este yacimiento, la presencia de Microtus brecciensis señala una edad más antigua que la propuesta por las dataciones de TL, dentro del Pleistoceno Medio. La comparación de algunas características biométricas entre las poblaciones de esta última especie de H-02 y de Áridos 1 permite además precisar que la edad del primero es más reciente que el segundo. Teniendo en cuenta que las dataciones disponibles para Áridos 1 (Panera et al., 2011) sitúan este yacimiento a finales del MIS 11, el yacimiento H-02 tuvo que formarse en el último cuarto del Pleistoceno Medio. Por consiguiente, las dataciones obtenidas por TL para el yacimiento H-02 parecen corresponder con edades mínimas de los sedimentos y no con su edad real

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

B-cell regeneration profile and minimal residual disease status in bone marrow of treated multiple myeloma patients

© 2021 by the authors.B-cell regeneration during therapy has been considered as a strong prognostic factor in multiple myeloma (MM). However, the effects of therapy and hemodilution in bone marrow (BM) B-cell recovery have not been systematically evaluated during follow-up. MM (n = 177) and adult (≥50y) healthy donor (HD; n = 14) BM samples were studied by next-generation flow (NGF) to simultaneously assess measurable residual disease (MRD) and residual normal B-cell populations. BM hemodilution was detected in 41 out of 177 (23%) patient samples, leading to lower total B-cell, B-cell precursor (BCP) and normal plasma cell (nPC) counts. Among MM BM, decreased percentages (vs. HD) of BCP, transitional/naïve B-cell (TBC/NBC) and nPC populations were observed at diagnosis. BM BCP increased after induction therapy, whereas TBC/NBC counts remained abnormally low. At day+100 postautologous stem cell transplantation, a greater increase in BCP with recovered TBC/NBC cell numbers but persistently low memory B-cell and nPC counts were found. At the end of therapy, complete response (CR) BM samples showed higher CD19− nPC counts vs. non-CR specimens. MRD positivity was associated with higher BCP and nPC percentages. Hemodilution showed a negative impact on BM B-cell distribution. Different BM B-cell regeneration profiles are present in MM at diagnosis and after therapy with no significant association with patient outcome.This work has been supported by the International Myeloma Foundation-Black Swan Research Initiative, the EuroFlow Consortium (grant LSHB-CT-2006-018708); Centro de Investigación Biomédica en Red de Cáncer (CIBER-ONC; Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER), numbers: CB16/12/00400, CB16/12/00233, CB16/12/00369, CB16/12/00489 and CB16/12/00480; grant from Bilateral Cooperation Program between Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES (Brasília/Brazil) and Dirección General de Políticas Universitárias (DGPU)-Ministério de Educación, Cultura y Deportes (Madrid/Spain) number DGPU 311/15; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro of Brazil (FAPERJ) numbers: E26/110.105/2014 and E26/102.191/2013; grant from Conselho Nacional de Desenvolvimento Científico e Tecnológico of Brazil (CNPQ), number: 400194/2014-7. R.M.d.P. was supported by a grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/DGPU), number: 000281/2016-06 and CAPES/PROEX 641/2018, Brazil; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro of Brazil (FAPERJ) number: E01/200/537/2018

Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

[EN]Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾107 cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.This work has been supported by the International Myeloma Foundation-Black Swan Research Initiative, the Red Temática de Investigación Cooperativa en Cáncer (RTICC); grant SA079U14 from the Consejería de Educación, Junta de Castilla y León, Valladolid, Spain and; grant DTS15/00119 from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain

Restos de caballos fósiles cuaternarios en la depresión Prados-Guatén (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.Peer reviewe

Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of

Caminho das letras: educação, formação e perspectivas

ial que se apresenta com o tema “Caminho das letras: Educação, Formação e Perspectivas”, partindo da vida escolar como aluno, chegando a atuação como professora, caracteriza-se também por uma reflexão teórica acerca do papel que as escolas cumprem na sociedade - será que servem como redutoras, ou apenas como indutoras da desigualdade social? A igualdade já deve começar em relação aos conhecimentos, conteúdos, de forma que contemplem suas aspirações, capacidades e possibilidades dos educandos, uma vez que o poder do capital refletiu também no sistema educacional, pois esta ficou com a tarefa de preparar mão-de-obra para a indústria, se preocupando apenas em atender ao mercado de trabalho, educando-se para seguir modelos, regras, se disciplinar e especializar. Deste modo, com base em textos trabalhados durante as aulas, vou teorizar minhas memórias, muitas não tão distantes. Neste trabalho, procuro relatar como compreendi o sentido da escola, se o seu papel é de formar ou apenas informar. Fiz-me esta questão, uma vez que Educação e instrução caminham juntas, completando o intelectual e o social, e assim a Gestão Escolar, há de ter representatividade, não ser meramente funcional. Dessa forma, uma Gestão Escolar com representatividade é democrática e autônoma, que envolve os diferentes atores da Educação (alunos, pais, professores, coordenação e direção). Deve garantir um ensino não fragmentado, proporcionar um intercâmbio entre as matérias, para que o aluno tenha uma visão unificada dos conhecimentos. Por fim, cheguei à conclusão entendendo que, o aluno não aprende por discursos, e sim pela vivência, muitos aprendizados são adquiridos com base nos relacionamentos, ou seja, nas interações e conflitos com o outro

Thyroid Hormone Economy in the Perinatal Mouse Brain: Implications for Cerebral Cortex Development.

Thyroid hormones (THs, T4 and the transcriptionally active hormone T3) play an essential role in neurodevelopment; however, the mechanisms underlying T3 brain delivery during mice fetal development are not well known. This work has explored the sources of brain T3 during mice fetal development using biochemical, anatomical, and molecular approaches. The findings revealed that during late gestation, a large amount of fetal brain T4 is of maternal origin. Also, in the developing mouse brain, fetal T3 content is regulated through the conversion of T4 into T3 by type-2 deiodinase (D2) activity, which is present from earlier prenatal stages. Additionally, D2 activity was found to be essential to mediate expression of T3-dependent genes in the cerebral cortex, and also necessary to generate the transient cerebral cortex hyperthyroidism present in mice lacking the TH transporter Monocarboxylate transporter 8. Notably, the gene encoding for D2 (Dio2) was mainly expressed at the blood-cerebrospinal fluid barrier (BCSFB). Overall, these data signify that T4 deiodinated by D2 may be the only source of T3 during neocortical development. We therefore propose that D2 activity at the BCSFB converts the T4 transported across the choroid plexus into T3, thus supplying the brain with active hormone to maintain TH homeostasis.This work was supported by the Spanish Ministry of Economy and Competitiveness (grant numbers SAF2011-25608, SAF2012-32491, and SAF2014-54919-R), the Center for Biomedical Research on Rare Diseases (CIBERER) of Instituto de Salud Carlos III under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases (project acronym THYRONERVE) and by Comunidad de Madrid (CAM; grant number S2010/BMD-2423). S.B.-L. is a recipient of a predoctoral fellowship and contract from the FPI program of the Plan Nacional de I+D+i. The cost of this publication has been paid in part by FEDER funds.Peer reviewe

Modelling of trihalomethanes and haloacetic acids during the drinking water treatment and in the distribution system of two towns

New and more stringent standards have been stablished or are under way in many countries for disinfection by-products (DBPs) in drinking water. The effort to comply with these new rules, maintaining microbiological security, may be quite unequal for each country since different water resources (surface or groundwater), water qualities and even climates will implicate different operational changes and, hence, costs. Thus, there is a need to estimate the factors influencing the formation of DBPs in real systems so that optimization of operational conditions can minimize them without a need for a dramatic shift for another treatment procedure. A study has been carried out on the drinking water treatment plants and distribution systems of two towns (Salamanca and Avila, Spain), from raw to tap water, over a one year period, in order to elaborate mathematical models for the presence of THMs and HAAs. Multivariate analysis has been performed for measurables and operational data from each sampling date: Water temperature, pH, T.O.C., UV-254, A.H.S. (aquatic humic substances), free and total chlorine, and chlorine dosages. The one year monitoring of both systems show that, on an average basis, the level of THMs and HAAs measured in the distribution system of Avila are nearly double those of Salamanca, so that 45% of cases exceed the E. U. standard of 100 µg/L THMs and 86% exceed the U.S.A. standard of 60 µg/L HAAs. For Salamanca 20% and 50% of cases exceed these standards, respectively. An early hypothesis for this was the higher level and different composition of TOC together with the higher chlorination dosages for Avila. However, regression analysis did not find linear correlation with TOC (or other related parameters, as AHS and UV-254). No linear correlation was found either between chlorination dosages and levels of THMs, but a positive one was obtained with HAAs levels for both systems. In spite of all this, the mathematical model for HAAs in Salamanca selected TOC, AHS and the rechlorination dosages practised at reservoirs. In line with the findings generally reported, a linear and positive dependence on temperature was observed for THMs and HAAs in Avila and HAAs in Salamanca. However, a non linear dependence was found for THMs in Salamanca, showing a curve with a maximum at 21,2 °C after which a sharp decrease of THMs was observed with increasing temperature. The possible influence of pH, a factor generally recognised of paramount importance, could not be demonstrated so that this variable is only reflected in one of the models. The homogeneity of the pH values measured along the period of study has hindered the quantitation of its possible influence. Four mathematical equations have been obtained to predict the levels of THMs and HAAs at any of the points studied for both systems. The variables selected for each model were: Water temperature (in all four models), pH for HHAs in Avila, time of residence for THMs in Salamanca and rechlorination dosages, TOC and AHS for HAAs in Salamanca