Rasgos morfologicos y petrologicos del paleokarst de la unidad superior del mioceno de la cuenca de Madrid

In the Madrid Basin, especially in the Southem part (Mesa de Ocaña), the Miocene- Pliocene stratigraphic boundary is defined by a paleokarst sculpted on the Miocene limestones. The development of the paleokarst was completed in three main successive stages. The first one was initiated when the lacustrine sedimentary complex, settled in the basin during the Turolian, dried out. Although the water table dropped, it was still close to the surface, as indicated by the location of sub-horizontal caves in the limestone formation. The proximity of the water table favored an encroachment of vegetation into the unlithified sediment. Conduits related to the plant roots, together with the horizontal caves, represent the most prominent dissolution features of the resulting «uncovered» karst. The second stage of karstification took place after the limestones folded. It was characterized by the formation of calcretes, which exhibit typical fabrics (laminar, pisoliths, etc.), on the previous profiles, providing evidence of a dry climatic stage. Karstic profiles scovered by calcretes~w ere buried by a Pliocene river system. In the south zone of the Mesa de Ocaña, far away of the fluvial complex, a third episode of karstification has been verified. This episode is defined by the accumulation of soils, basically in the synclines, which caused the dissolution and brecciation of the substrate, as it is reflected in a third type of profiles, called «brechoides». These features are consistent with a humid climate. Finally, al1 types of karst were buried by a laminar calcrete formed at the latest Pliocene. Therefore, the polyphase development of the paleokarstic surface lasted almost al1 the Pliocene. Nevertheless, figures on the order of lo5 years are envisaged as reliable to assess the duration of the first phase, the only one evenly affecting the limestone formations.En la Cuenca de Madrid y, especialmente, en la zona sur (Mesa de Ocaña), la discontinuidad estratigráfica que define el límite Mioceno-Plioceno está representada por una superficie paleokárstica desarrollada sobre las calizas de la Unidad Superior del Mioceno. El paleokarst sufrió una evolución polifásica dentro de la cual se han destacado tres episodios principales. El primero, que afectó por igual a todo el conjunto carbonático, se inició con la desecación de los sistemas lacustres instalados en el área durante el Turoliense. El nivel freático se mantuvo próximo a la superficie del terreno, como se constata por la situación de cuevas horizontales en las calizas. La superficialidad de la tabla de agua, junto a la falta de litificación del sedimento, propició una extensiva colonización vegetal. Asociado a las raíces de las plantas, se originó un conjunto de tubos que, junto con las cuevas horizontales, configuran un modelado característico del tipo de perfiles kársticos denominados «descubiertos». La evolución posterior del karst tuvo lugar tras el plegamiento de las calizas. Esta segunda etapa se caracterizó por la formación local de calcretas con sus fábricas características (laminar, pisolítica, etc.) sobre los perfiles anteriores, lo que evidencia un régimen climático árido. Más tarde, la tipología de perfiles «cubiertos por calcretas» resultante fue enterrada por el sistema fluvial plioceno que se instaló en el NE de la Mesa de Ocaña. En la zona sur, más alejada de los depocentros deposicionales, se constata un tercer episodio evolutivo definido por la acumulación de suelos, fundamentalmente en los sinclinales. Bajo esta cubierta edáfica tuvo lugar una intensa disolución y brechificación del sustrato que se ha reflejado en un tercer tipo de perfiles, denominados «brechoides» y que indican'an condiciones climáticas húmedas. Finalmente, todo el conjunto fue fosilizado por las costras calcáreas que se formaron a finales del Plioceno. El estudio de este paleokarst permite, por un lado, desvelar los procesos diagenéticos principales que han experimentado las calizas de la Unidad Superior del Mioceno desde las etapas iniciales de exposición subaérea y, por otro, determinar que dicha exposición se prolongó durante todo el Plioceno. No obstante, la duración de la primera fase generalizada de karstificación fue más breve, ya que las evidencias apuntan a cifras del orden de lo5 años

Geochemistry and microbial communities in Salar de Pajonales and Salar de Gorbea, Northern Chile: Influence on the gypsum microbialites formation

Pajonales y Gorbea son dos salares andinos de Chile, compuestos mayoritariamente de yeso, y poseen lagunas de un amplio rango de salinidades, índices de saturación (IS) de yeso y pH. Hay varios estudios que han abordado la geología de los salares de forma general, pero la geoquímica, petrografía y mineralogía de estos depósitos salinos han sido poco estudiado. El objetivo es comparar la información geoquímica de las aguas de las lagunas subsaturadas y sobresaturadas de yeso de ambos salares para identificar correlaciones entre la mineralogía de las comunidades microbianas y la hidroquímica que permitan desvelar el origen del yeso. En Pajonales, el yeso precipita: en lagunas subsaturadas con pH (7,4-8,1), salinidad (1,9-4,8 %) y predominancia de α-Proteobacteria (64%) en tapices microbianos. De otra manera, en Gorbea no se reconoce una relación significativa entre la precipitación de yeso, pH (1,8 a 4,5), salinidad (0,6-15 %) y predominancia de α+γ-Proteobacteria (90%). Cabe destacar que en aguas sobresaturadas se observó que los microbialitos de yeso están colonizados por fotótrofos en Pajonales (Cianobacterias) y en Gorbea (Diatomeas). Estos resultados sugieren que las comunidades de α-Proteobacteria en aguas subsaturadas y de fotótrofos en aguas sobresaturadas pueden jugar un papel en la precipitación de yeso.Pajonales and Gorbea are two Andean salt flats in Chile, composed mainly of gypsum, and have lagoons with a wide range of salinities, gypsum saturation indices (SI), and pH. There are several studies that have addressed the geology of the salt flats in a general way, but the geochemistry, petrography and mineralogy of these salt deposits have been little studied. The objective is to compare geochemical information of the waters of the undersaturated and oversaturated gypsum lagoons of both salt flats to identify correlations between the mineralogy of the microbial communities and the hydrochemistry that allows to reveal the origin of the gypsum. In Pajonales, gypsum precipitates: in subsaturated lagoons with pH (7.4-8.1), salinity (1.9-4.8%) and a predominance of α-Proteobacteria (64%) in microbial mats. Otherwise, in Gorbea a significant relationship between gypsum precipitation, pH (1.8 to 4.5), salinity (0.6-15%) and predominance of α + γ-Proteobacteria (90%) is not recognized. It should be noted that in supersaturated waters, gypsum microbialites are colonized by phototrophs in Pajonales (Cyanobacteria) and Gorbea (diatoms). These results suggested that α-Proteobacteria communities in subsaturated waters and phototrophs in supersaturated waters may play a role in gypsum precipitation.Depto. de Mineralogía y PetrologíaFac. de Ciencias GeológicasTRUEProyecto Donaciones Minera Escondida Ltda.Beca Doctorado-ANIDpu

Biomaterials and regenerative technologies used in bone regeneration in the craniomaxillofacial region: Consensus report of group 2 of the 15th European Workshop on Periodontology on Bone Regeneration

Geistlich Pharma A

ALDH4A1 is an atherosclerosis auto-antigen targeted by protective antibodies

Cardiovascular disease (CVD) is the leading cause of mortality in the world, with most CVD-related deaths resulting from myocardial infarction or stroke. The main underlying cause of thrombosis and cardiovascular events is atherosclerosis, an inflammatory disease that can remain asymptomatic for long periods. There is an urgent need for therapeutic and diagnostic options in this area. Atherosclerotic plaques contain autoantibodies, and there is a connection between atherosclerosis and autoimmunity. However, the immunogenic trigger and the effects of the autoantibody response during atherosclerosis are not well understood. Here we performed high-throughput single-cell analysis of the atherosclerosis-associated antibody repertoire. Antibody gene sequencing of more than 1,700 B cells from atherogenic Ldlr and control mice identified 56 antibodies expressed by in-vivo-expanded clones of B lymphocytes in the context of atherosclerosis. One-third of the expanded antibodies were reactive against atherosclerotic plaques, indicating that various antigens in the lesion can trigger antibody responses. Deep proteomics analysis identified ALDH4A1, a mitochondrial dehydrogenase involved in proline metabolism, as a target antigen of one of these autoantibodies, A12. ALDH4A1 distribution is altered during atherosclerosis, and circulating ALDH4A1 is increased in mice and humans with atherosclerosis, supporting the potential use of ALDH4A1 as a disease biomarker. Infusion of A12 antibodies into Ldlr mice delayed plaque formation and reduced circulating free cholesterol and LDL, suggesting that anti-ALDH4A1 antibodies can protect against atherosclerosis progression and might have therapeutic potential in CVD.Ministerio de Economía y Competitividad (SVP-2014-068289); P.D. was supported by an AECC grant (AIO 2012, Ayudas a Investigadores en Oncología 2012); A.S.-B. is a Juan de la Cierva researcher (IJC2018-035279-I); I.M.-F. was a fellow of the research training program funded by Ministerio de Economía y Competitividad (SVP-2014-068216); and A.R.R. and J.V. are supported by Centro Nacional de Investigaciones Cardiovasculares (CNIC). The project leading to these results has received funding from la Caixa Banking Foundation under the project code HR17-00247 and from SAF2016-75511-R and PID2019-106773RB-I00 grants to A.R.R. (Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–201

Dual Mechanism for the Translation of Subgenomic mRNA from Sindbis Virus in Infected and Uninfected Cells

Infection of BHK cells by Sindbis virus (SV) gives rise to a profound inhibition of cellular protein synthesis, whereas translation of viral subgenomic mRNA that encodes viral structural proteins, continues for hours. To gain further knowledge on the mechanism by which this subgenomic mRNA is translated, the requirements for some initiation factors (eIFs) and for the presence of the initiator AUG were examined both in infected and in uninfected cells. To this end, BHK cells were transfected with different SV replicons or with in vitro made SV subgenomic mRNAs after inactivation of some eIFs. Specifically, eIF4G was cleaved by expression of the poliovirus 2A protease (2Apro) and the alpha subunit of eIF2 was inactivated by phosphorylation induced by arsenite treatment. Moreover, cellular location of these and other translation components was analyzed in BHK infected cells by confocal microscopy. Cleavage of eIF4G by poliovirus 2Apro does not hamper translation of subgenomic mRNA in SV infected cells, but bisection of this factor blocks subgenomic mRNA translation in uninfected cells or in cell-free systems. SV infection induces phosphorylation of eIF2α, a process that is increased by arsenite treatment. Under these conditions, translation of subgenomic mRNA occurs to almost the same extent as controls in the infected cells but is drastically inhibited in uninfected cells. Notably, the correct initiation site on the subgenomic mRNA is still partially recognized when the initiation codon AUG is modified to other codons only in infected cells. Finally, immunolocalization of different eIFs reveals that eIF2 α and eIF4G are excluded from the foci, where viral RNA replication occurs, while eIF3, eEF2 and ribosomes concentrate in these regions. These findings support the notion that canonical initiation takes place when the subgenomic mRNA is translated out of the infection context, while initiation can occur without some eIFs and even at non-AUG codons in infected cells

Exploring the response of a key Mediterranean gorgonian to heat stress across biological and spatial scales

Understanding the factors and processes that shape intra-specific sensitivity to heat stress is fundamental to better predicting the vulnerability of benthic species to climate change. Here, we investigate the response of a habitat-forming Mediterranean octocoral, the red gorgonian Paramuricea clavata (Risso, 1826) to thermal stress at multiple biological and geographical scales. Samples from eleven P. clavata populations inhabiting four localities separated by hundreds to more than 1500 km of coast and with contrasting thermal histories were exposed to a critical temperature threshold (25 degrees C) in a common garden experiment in aquaria. Ten of the 11 populations lacked thermotolerance to the experimental conditions provided (25 days at 25 degrees C), with 100% or almost 100% colony mortality by the end of the experiment. Furthermore, we found no significant association between local average thermal regimes nor recent thermal history (i.e., local water temperatures in the 3 months prior to the experiment) and population thermotolerance. Overall, our results suggest that local adaptation and/or acclimation to warmer conditions have a limited role in the response of P. clavata to thermal stress. The study also confirms the sensitivity of this species to warm temperatures across its distributional range and questions its adaptive capacity under ocean warming conditions. However, important inter-individual variation in thermotolerance was found within populations, particularly those exposed to the most severe prior marine heatwaves. These observations suggest that P. clavata could harbor adaptive potential to future warming acting on standing genetic variation (i.e., divergent selection) and/or environmentally-induced phenotypic variation (i.e., intra- and/or intergenerational plasticity).European Commission SEP-210597628- FutureMARES, MCIU/AEI/FEDER RTI2018-095346-BI00, Spanish government through the `Severo Ochoa Centre of Excellence' accreditation CEX2019-000928-S , Interreg Med Programme 5216|5MED18_3.2_M23_007, 1MED15_3.2_M2_ 337, Spanish Government FPU15/05457, Fundacao para a Ciencia e a Tecnologia (FCT) LA/P/0101/2020 , DivRestore/0013/2020, Marine Conservation research group 2017 SGR 1521, postdoctoral fellowship of project HABMAR - European Maritime and Fisheries Fund of the Operational Program MAR 2020 for Portugal MAR-01.04.02-FEAMP-0018info:eu-repo/semantics/publishedVersio

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide versus dolutegravir /abacavir/lamivudine in antiretroviral-naïve adults (SYMTRI): a multicenter randomized open-label study (PReEC/RIS-57)

D/C/F/TAF is the reference for combination therapy based on protease inhibitors but has not been compared with regimens containing integrase inhibitors as initial ART. We could not demonstrate D/C/F/TAF noninferiority relative to DTG/ABC/3TC, although both regimens were similarly well tolerated. Background Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naive patients are lacking. Methods Adult (>18 years old) human immunodeficiency virus-infected antiretroviral-naive patients (HLA-B*5701 negative and hepatitis B virus negative), with viral load (VL) >= 500 c/mL, were centrally randomized to initiate D/C/F/TAF or dolutegravir/abacavir/lamivudine (DTG/3TC/ABC) after stratifying by VL and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL 100 000 copies/mL, and 13% had <200 CD4 cells/mu L. Median weight was 73 kg and median body mass index was 24 kg/m(2). At 48 weeks, 79% (D/C/F/TAF) versus 82% (DTG/3TC/ABC) had VL <50 c/mL (difference, -2.4%; 95% confidence interval [CI], -11.3 to 6.6). Eight percent versus four percent experienced virologic failure but no resistance-associated mutations emerged. Four percent versus six percent had drug discontinuation due to adverse events. In the per-protocol analysis, 94% versus 96% of patients had VL <50 c/mL (difference, -2%; 95% CI, -8.1 to 3.5). There were no differences in CD4 cell count or weight changes. Conclusions We could not demonstrate the noninferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial antiretroviral therapy, although both regimens were similarly well tolerated

Comparison of next-generation sequencing (NGS) and next-generation flow (NGF) for minimal residual disease (MRD) assessment in multiple myeloma

Detecting persistent minimal residual disease (MRD) allows the identification of patients with an increased risk of relapse and death. In this study, we have evaluated MRD 3 months after transplantation in 106 myeloma patients using a commercial next-generation sequencing (NGS) strategy (LymphoTrack®), and compared the results with next-generation flow (NGF, EuroFlow). The use of different marrow pulls and the need of concentrating samples for NGS biased the applicability for MRD evaluation and favored NGF. Despite that, correlation between NGS and NGF was high (R = 0.905). The 3-year progression-free survival (PFS) rates by NGS and NGF were longer for undetectable vs. positive patients (NGS: 88.7% vs. 56.6%; NGF: 91.4% vs. 50%; p < 0.001 for both comparisons), which resulted in a 3-year overall survival (OS) advantage (NGS: 96.2% vs. 77.3%; NGF: 96.6% vs. 74.9%, p < 0.01 for both comparisons). In the Cox regression model, NGS and NGF negativity had similar results but favoring the latter in PFS (HR: 0.20, 95% CI: 0.09-0.45, p < 0.001) and OS (HR: 0.21, 95% CI: 0.06-0.75, p = 0.02). All these results reinforce the role of MRD detection by different strategies in patient prognosis and highlight the use of MRD as an endpoint for multiple myeloma treatment