Tracking magmatism and oceanic change through the early Aptian Anoxic Event (OAE 1a) to the late Aptian: Insights from osmium isotopes from the westernmost Tethys (SE Spain) Cau Core

Some of the major Carbon cycle perturbations of the Phanerozoic occurred during the Aptian, in relation to magmatism. The highest temperatures reconstructed for the Cretaceous Period correspond to the Oceanic Anoxic Event of the early Aptian (OAE 1a), an episode of accelerated global change. Here we present a chemostratigraphic study based on osmium isotopes integrated with high-resolution Carbon-Oxygen stable isotope data from the Cau Core (Western Tethys, SE Spain), including a 6.4 Ma record from the early to the late Aptian. This high-resolution study of the continuous and expanded Cau section permits a thorough understanding of the duration of the Aptian events, as well as an evaluation of the mechanisms triggering the abrupt changes of the global carbon and osmium cycles and their interdependence. Here we show that the Large Igneous Province (LIP) Aptian magmatism initiated 550–750 kyr prior to the OAE 1a, and persisted for 1.4 Myr after the event, influencing the composition of seawater for 2.8 Myr. We show a continuous Os isotope record encompassing the OAE 1a and the late Aptian for the first time, and demonstrate that the recovery from the exceptionally unradiogenic composition of seawater Os produced by the dominance of the Ontong Java Plateau volcanism, was slow. Our results demonstrate the different time duration of some events, and the asynchronous relationship between the carbon and osmium cycles

Progradation of a shallow carbonate platform developed on a fault-block in the Western Tethys (lower Aptian, Sierra de Bedmar-Jódar, Prebetic of Jaén, Spain).

The Middle Member of the Llopis Fm in the Sierra de Bedmar-Jódar Unit of the Prebetic Zone of Jaén (southern Spain) was deposited on a shallow-marine platform of the Southern Iberian Continental Margin during the earliest Aptian. Detailed field logging of nine stratigraphic sections and facies mapping have allowed seven lithofacies associations (L1–L6) to be distinguished, one siliciclastic (L1) and five carbonate facies (L2–6). The succession is composed of eight consecutive elemental sequences of lithofacies associations L1–L6. Each elemental sequence is interpreted as representing one episode of shallowing-upwards carbonate deposition in a very shallow platform-lagoon that was bounded shoreward by clastic/ooid bars and passed seaward either to stromatoporoid bioconstructions (bioherms and biostromes) or rudist biostromes. The successive elemental sequences show north-eastward progradational geometries. Three phases of platform development are identified: (1) installation of the shallow platform; (2) development of a lagoon bounded by a stromatoporoid barrier and (3) development of an Urgonian-type platform dominated by rudists. During the early Aptian, the Bedmar-Jódar platform was partially isolated from the rest of the Prebetic platform and showed overall progradation towards the NE, in contrast to the general south-eastward progradational trend of the Prebetic platform. Sedimentation was controlled by rift-generated extensional tectonics that resulted in tilting of the platform block, causing the deviation of progradation from the general trends of the Prebetic Platform. In addition, climatic influence is inferred from the presence of siliciclastic sediments derived from weathering of the hinterland, which restricted the carbonate factory.Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEUniversidad de JaénSecretaría de Estado de I + D + iJunta de Andalucíapu

Stratigraphy and chemostratigraphy of the Valanginian (pro parte) from Loma Solana, Sierra de Quípar (External Subbetic, Cehegín, Murcia)

The stratigraphy, biostratigraphy and geochemistry (C stable isotopes and RSTE trace elements) of a succession of Valanginian age outcropping in Loma Solana (External Subbetic) is presented. The succession is composed of two local sections, one cropping out to the west of Cehegín (Murcia) and another in the Garranchal gorge, to the SSW of this locality. The lithology consists of marl and marlstone rhythmically interbedded, which is typical of the Carretero Fm of the Subbetic. The ammonite zones and subzones of the middle- late early Valanginian and the complete late Valanginian, except for the lattermost part, have been identified, without any evidence of stratigraphic discontinuity between the two local sections. The δ13C curve show a similar shape to those of the same age obtained in other basins and the positive excursion of the δ13C characterizing the Weissert episode of environmental change (EECWeissert) has been identified. The RSTE, redox sensitive trace elements, analyzed do not show any particular increase as is typical of anoxic events and consequently conclude that anoxia due not exist in this part of the Subbetic basin during this EECSe presenta el estudio estratigráfico, bioestratigráfico y geoquímico de una sucesión del Valanginiense que aflora en Loma Solana (Subbético Externo). Se trata de una sección compuesta de dos secciones parciales, una de ellas levantada al oeste de Cehegín (Murcia) y la otra en el barranco del Garranchal, al SSO de dicha localidad. La litología,margas y margocalizas en alternancia rítmica, es la típica de la Fm. Carretero, a la que corresponde. Se identifican las zonas y subzonas de ammonites de la parte media-alta del Valanginiense inferior y de todo el Valanginiense superior, excepto la parte más terminal del mismo, sin que se haya denotado discontinuidad alguna entre una sección y otra. La curva de valores de δ13C muestra una forma similar a la obtenida en otras cuencas para la misma edad y en ella se puede identificar la excursión positiva del δ13C que caracteriza el episodioWeissert de cambio ambiental. Los elementos traza analizados, sensibles a cambios en las condiciones redox del medio sedimentario (elementos RSTE), no indican que hubiera condiciones anóxicas en el mismo durante este episodio de cambio ambienta

Body composition changes after a weight loss intervention: A 3-year follow-up study

Studies comparing different types of exercise-based interventions have not shown a consistent effect of training on long-term weight maintenance. The aim of this study was to compare the effects of exercise modalities combined with diet intervention on body composition immediately after intervention and at 3 years’ follow-up in overweight and obese adults. Two-hundred thirty-nine people (107 men) participated in a 6-month diet and exercise-based intervention, split into four randomly assigned groups: strength group (S), endurance group (E), combined strength and endurance group (SE), and control group (C). The body composition measurements took place on the first week before the start of training and after 22 weeks of training. In addition, a third measurement took place 3 years after the intervention period. A significant interaction effect (group × time) (p = 0.017) was observed for the fat mass percentage. It significantly decreased by 5.48 ± 0.65%, 5.30 ± 0.65%, 7.04 ± 0.72%, and 4.86 ± 0.65% at post-intervention for S, E, SE, and C, respectively. Three years after the intervention, the fat mass percentage returned to values similar to the baseline, except for the combined strength and endurance group, where it remained lower than the value at pre-intervention (p < 0.05). However, no significant interaction was discovered for the rest of the studied outcomes, neither at post-intervention nor 3 years later. The combined strength and endurance group was the only group that achieved lower levels of fat mass (%) at both post-intervention and 3 years after intervention, in comparison with the other groups.This work received financial support from the Ministerio de Ciencia e Innovación, Convocatoria de Ayudas I+D 2008, Proyectos de Investigación Fundamental No Orientada, del VI Plan de Investigación Nacional 2008–2011 (Contract: DEP2008-06354-C04-01). This study is registered at www.clinicaltrials.gov (ID: NCT0111685

Effects of classical PKC activation on hippocampal neurogenesis and cognitive performance: mechanism of action

Hippocampal neurogenesis has widely been linked to memory and learning performance. New neurons generated from neural stem cells (NSC) within the dentate gyrus of the hippocampus (DG) integrate in hippocampal circuitry participating in memory tasks. Several neurological and neuropsychiatric disorders show cognitive impairment together with a reduction in DG neurogenesis. Growth factors secreted within the DG promote neurogenesis. Protein kinases of the protein kinase C (PKC) family facilitate the release of several of these growth factors, highlighting the role of PKC isozymes as key target molecules for the development of drugs that induce hippocampal neurogenesis. PKC activating diterpenes have been shown to facilitate NSC proliferation in neurogenic niches when injected intracerebroventricularly. We show in here that long-term administration of diterpene ER272 promotes neurogenesis in the subventricular zone and in the DG of mice, affecting neuroblasts differentiation and neuronal maturation. A concomitant improvement in learning and spatial memory tasks performance can be observed. Insights into the mechanism of action reveal that this compound facilitates classical PKCα activation and promotes transforming growth factor alpha (TGFα) and, to a lesser extent, neuregulin release. Our results highlight the role of this molecule in the development of pharmacological drugs to treat neurological and neuropsychiatric disorders associated with memory loss and a deficient neurogenesis.Ministerio de Ciencia, Innovación y Universidades de España (MICINN) RTI-2018-099908-B-C21 y RTI-2018-099908-B-C22Ministerio de Ciencia, Innovación y Universidades de España y Fondos FEDER de la Unión Europea (MICINN/FEDER) BFU2016-75038RConsejería de Economía, Conocimiento, Empresas y Universidades de la Junta de Andalucía y Fondos FEDER. FEDER-UCA18-10664

Doñana, diversidad y ciencia

144 páginasLa biodiversidad es más que la suma de los elementos que componen el mundo vivo; también son biodiversidad las relaciones entre esos elementos, los procesos ecológicos que hacen posible su existencia y los procesos evolutivos que los han originado. […] Los seres humanos necesitamos a la biodiversidad más que ella a nosotros, ya que es la responsable de que la Tierra funcione de una manera satisfactoria. […] El entramado de la vida se ocupa de regular la composición de la atmósfera (y con ella, el clima), de depurar el aire y el agua, de hacer fértil al suelo, de evitar riadas y avalanchas, de polinizar las cosechas, de reducir las plagas, etc. Por todo ello es indispensable conservar la biodiversidad, hoy amenazada.” (Miguel Delibes) Doñana, diversidad y ciencia es un paseo conceptual por el espacio natural más emblemático de Europa. La esencia de un mito a través de decenas de fotografías… Un acercamiento respetuoso a la diversidad de sus conceptos, un paseo por la esencia de su historia y una curiosa aproximación a la ciencia que genera hoy en día. En este recorrido descubriremos el carácter distintivo de algunos de los parajes de la reserva, sus matices más interesantes, las texturas y las formas más sorprendentes de la naturaleza, sus colores y conjuntos, sus transformaciones en las últimas décadas y la influencia de la presencia humana en el privilegiado ecosistema de la Reserva Biológica de Doñana

Potential of Native Microalgae from the Peruvian Amazon on the Removal of Pollutants

Environmental pollution is a severe and common problem in all the countries worldwide. Various physicochemical technologies and organisms (e.g., plants, microorganisms, etc.) are used to address these environmental issues, but low-cost, practical, efficient, and effective approaches have not been available yet. Microalgae offer an attractive, novel, and little-explored bioremediation alternative because these photosynthetic organisms can eliminate pathogenic microorganisms and remove heavy metals and toxic organic compounds through processes still under study. Our research team has conducted some experiments to determine the bioremediation potential of native microalgae on some pollutant sources (i.e., leachate and wastewater) and its ability to remove hazardous chemical compounds. Therefore, in this chapter, we provide the results of our research and updated information about this exciting topic. Experiments were conducted under controlled culture conditions using several native microalgae species, variable time periods, different pollutant sources, and hazardous chemicals such as ethidium bromide. The results indicated that native microalgae can remove pollutants (i.e., phosphorus, ammonia, etc.) of wastewater, leachate, and some hazardous chemical compounds such as ethidium bromide. In conclusion, native microalgae have an excellent potential for removing several pollutants and, consequently, could be used to develop bioremediation technologies based on native microalgae from the Peruvian Amazon

Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies

[Background] There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection.[Methods] This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007–2016). The impact of ED and factors associated with mortality were assessed.[Results] Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48–10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94–9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14–5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48–10.61), and prior surgery (OR, 0.29; 95% CI, 0.08–0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16–1.53).[Conclusions] Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.This research forms part of an activity that has received funding from EIT Health. EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union that receives support from the European Union´s Horizon 2020 Research and Innovation Program. This study has been cofunded by the European Regional Development Fund. E. M.-G. (PI18/01061), P. P.-A. (“Rio Hortega” contract CM18/00132), M. F.-R. (“Miguel Servet” contract CP18/00073), and C. G.-V. (FIS PI18/01061) have received research grants from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III.Peer reviewe

Identification of 1,2,3-triazolium salt-based inhibitors of Leishmania infantum trypanothione disulfide reductase with enhanced antileishmanial potency in cellulo and increased selectivity

N-methylation of the triazole moiety present in our recently described triazole-phenyl-thiazole dimerization disruptors of Leishmania infantum trypanothione disulfide reductase (LiTryR) led to a new class of potent in- hibitors that target different binding sites on this enzyme. Subtle structural changes among representative library members modified their mechanism of action, switching from models of classical competitive inhibition to time- dependent mixed noncompetitive inhibition. X-ray crystallography and molecular modeling results provided a rationale for this distinct behavior. The remarkable potency and selectivity improvements, particularly against intracellular amastigotes, of the LiTryR dimerization disruptors 4c and 4d reveal that they could be exploited as leishmanicidal agents. Of note, L. infantum promastigotes treated with 4c significantly reduced their low- molecular-weight thiol content, thus providing additional evidence that LiTryR is the main target of this novel compound.This work has been financially supported by the Spanish MICINN (Projects PID2019-104070RB-C21, PID2019-104070RB-C22 and PID2020-115331 GB-I00), the Spanish Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC, Projects CSIC-PIE-201980E100 and CSIC-PIE-201980E028), and the Comunidad de Madrid (PLATESA2-CM ref. S-2018/BAA-4370). The Spanish MEC is also acknowledged for FPU grants to A. R. and to J.C.G. P.A.S.M. thanks to the Division of Physio- logical Chemistry and the Otto-Loewi Research Center of the Medical University of Graz for their support with the scienfic cluster where the calculations contained in this work were run. We thank Ricardo Lau- reano-Rodríguez, Juan Antonio Rodríguez-Gutierrez, and Laura Lagar- tera for technical assistance with SPR experiments.Peer reviewe

Arabidopsis thaliana SPF1 and SPF2 are nuclear-located ULP2-like SUMO proteases that act downstream of SIZ1 in plant development

Post-translational modifiers such as the small ubiquitin-like modifier (SUMO) peptide act as fast and reversible protein regulators. Functional characterization of the sumoylation machinery has determined the key regulatory role that SUMO plays in plant development. Unlike components of the SUMO conjugation pathway, SUMO proteases (ULPs) are encoded by a relatively large gene family and are potential sources of specificity within the pathway. This study reports a thorough comparative genomics and phylogenetic characterization of plant ULPs, revealing the presence of one ULP1-like and three ULP2-like SUMO protease subgroups within plant genomes. As representatives of an under-studied subgroup, Arabidopsis SPF1 and SPF2 were subjected to functional characterization. Loss-of-function mutants implicated both proteins with vegetative growth, flowering time, and seed size and yield. Mutants constitutively accumulated SUMO conjugates, and yeast complementation assays associated these proteins with the function of ScUlp2 but not ScUlp1. Fluorescence imaging placed both proteins in the plant cell nucleoplasm. Transcriptomics analysis indicated strong regulatory involvement in secondary metabolism, cell wall remodelling, and nitrate assimilation. Furthermore, developmental defects of the spf1-1 spf2-2 (spf1/2) double-mutant opposed those of the major E3 ligase siz1 mutant and, most significantly, developmental and transcriptomic characterization of the siz1 spf1/2 triple-mutant placed SIZ1 as epistatic to SPF1 and SPF2.We thank Mark Hochstrasser (Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT, USA) for kindly providing the ulp1-ts yeast mutant strain. This research was funded by FEDER (through COMPETE), and by Fundacao para a Ciencia e Tecnologia (FCT), within the scope of project SUMOdulator (FCOMP-01-0124-FEDER-028459 and PTDC/BIA-PLA/3850/2012). PHC was supported by FCT (SFRH/BD/44484/2008). HA and FF were supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000007 and Norte-01-0145-FEDER-000008, respectively). The work was supported by FEDER through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT, within the framework of projects 'Rede de Investigacao em Biodiversidade e Biologia Evolutiva' (POCI-01-0145-FEDER-006821) and 'Institute for Research and Innovation in Health Sciences' (POCI-01-0145-FEDER-007274). This research was also supported by a grant from the Spanish Ministerio de Ciencia y Tecnologia (AGL2016-75819-C2-1-R) and FEDER (PCQ, AGC, ERB)