Calcarenitas con Microcodium del Paleoceno inferior en áreas hemipelágicas de la Zona Subbética, SE de España: isótopos de Sr, área fuente e implicaciones paleogeográficas

The Danian−early Selandian Olivares and Majalcorón formations are two calcarenite units rich in Microcodium remains that were accumulated in a marine hemipelagic setting of the Subbetic Zone (Betic Cordillera, southern Spain). Their outcrops are restricted to relatively small areas surrounded by uplifted Jurassic calcareous massifs, some of them with volcanic intercalations. The calcarenites contain lithoclasts of Lower Jurassic and lowermost Cretaceous age, and the 87 Sr/ 86 Sr isotopic ratios of the Microcodium remains suggest that they were originated in roots of plants that grew on Lower Jurassic carbonates. These facts entail that the Microcodium remains came from the calcareous massifs adjacent to their outcrops, the upper parts of which were subaerially exposed and colonized by Microcodium -producing plants during the Danian−early Selandian interval. The subaerial exposure of these massifs may have resulted from a coeval tectonic reactivation of Mesozoic syn-rift faults and folds, a eustatic sea level fall, or a combination of both processesLas formaciones Olivares y Majalcorón del Daniense-Selandiense inferior son unidades de calcarenitas ricas en restos de Microcodium acumuladas en un ambiente marino hemipelágico de la Zona Subbética (Cordillera Bética). Sus afloramientos están restringidos a áreas relativamente pequeñas rodeadas por elevados macizos de carbonatos jurásicos, algunos de ellos con intercalaciones volcánicas. Las calcarenitas contienen litoclastos del Jurásico Inferior y de la parte más baja del Cretácico, y los valores isotópicos 87 Sr/ 86 Sr de los restos de Microcodium sugieren que los mismos se originaron en raíces de plantas que crecían sobre carbonatos del Jurásico Inferior. Estos hechos implican que los restos de Microcodium proceden de los macizos carbonatados adyacentes a sus afloramientos, cuyas partes superiores estarían expuestas subaéreamente y colonizadas por plantas productoras de Microcodium durante el Daniense-Selandiense inferior. La exposición subaérea de dichos macizos pudo deberse a una reactivación tectónica de fallas y pliegues mesozoicos preexistentes, a un descenso eustático del nivel del mar, o a una combinación de ambos proceso

Etude de l'effet de la colonisation des nouveau-nés par des souches de Escherichia coli génotoxiques sur le développement et la fonctionnalité de la barrière intestinale

Au cours du développement post-natal, le microbiote intestinal interagit intimement avec l'hôte et module à la fois la différenciation de l'épithélium intestinal et la maturation du système immunitaire. Hôte commun de la microflore commensale intestinale de l'Homme et des animaux à sang chaud, E. coli s'établit dans le tractus digestif dès les premières heures ou jours qui suivent la naissance. E. coli est alors une des espèces bactériennes dominantes de la flore du nouveau-né avant de devenir la bactérie aérobie facultative prédominante au sein du microbiote adulte. Certaines souches commensales de E. coli sont capables d'induire des dommages à l'ADN dans les entérocytes. La génotoxicité des ces souches résulte de la production d'une toxine, la Colibactine, synthétisée à partir de synthases de polycétides et de peptides non ribosomaux. Cette voie de biosynthèse est codée par un îlot génomique appelé pks. Plusieurs études épidémiologiques récentes montrent que plus de 30% des jeunes enfants âgés de trois jours sont colonisés par des E. coli qui portent l'îlot pks. Afin d'analyser les effets à long terme de la colonisation précoce des nouveau-nés par des souches de E. coli génotoxiques, nous avons développé un modèle animal expérimental qui mime la transmission naturelle des E. coli du microbiote de la mère au nouveau-né. Pour cela, des femelles rats gestantes sont gavées avec une souche commensale humaine génotoxique (E. coli WT), son mutant isogénique non génotoxique (E. coli DeltaclbA) ou le mutant complémenté (E. coli DeltaclbA+clbA) pour lequel la production de la Colibactine a été restaurée. Après la naissance, la transmission des souches bactériennes et la persistance de la colonisation chez les nouveau-nés ont été évaluées. En parallèle, les dommages à l'ADN occasionnés par ces souches sur l'épithélium intestinal ont été comparés sur une période de 100 jours. Enfin, le développement et la maturation de l'épithélium intestinal ainsi que sa fonction de barrière ont été analysés sur cette même période. Les souches de E. coli, produisant ou non la Colibactine, sont transmises à la descendance et colonisent de manière stable le tractus digestif tout au long de la vie de l'animal. Dès le deuxième jour après la naissance, des cassures double-brin de l'ADN (CDB) ont été observées dans les entérocytes des ratons colonisés par la souche de E. coli WT ou E. coli DeltaclbA+clbA complémentée mais sont absentes chez les nouveau-nés colonisés par le mutant E. coli DeltaclbA. Si de manière surprenante, aucune CDB n'a été détectée chez ces rats devenus adultes (100 jours), une fraction des cellules en mitose présente en revanche des signes de persistance des CDB : des ponts anaphasiques sont observés chez les animaux adultes colonisés par des souches génotoxiques. L'étude des conséquences du portage à long terme de souches génotoxiques sur le développement de l'épithélium intestinal, a révélé une augmentation significative de la prolifération et de l'apoptose des entérocytes corrélée avec une augmentation de la vitesse de migration de ces cellules épithéliales le long de l'axe crypte-villosité chez les animaux exposés à des souches génotoxiques depuis la naissance. De plus, une augmentation du nombre des cellules entéroendocrines et des cellules de Paneth a été constatée chez ces mêmes animaux. Les répercussions des perturbations précédemment observées sur la fonction de la barrière intestinale ont été analysées ex vivo en chambres de Ussing et montrent une augmentation de la perméabilité intestinale chez les rats colonisés depuis la naissance par des souches génotoxiques en comparaison à des animaux colonisés par le mutant non génotoxique. Ainsi, la colonisation du nouveau-né par des E. coli génotoxiques altère non seulement le développement et la maturation de l'épithélium intestinal à l'âge adulte mais également son intégrité. Ces modifications ont clairement des conséquences physiopathologiques pour l'hôte qui dépassent une prédisposition au développement de cancers colorectaux.During early development, intestinal microbiota intimately interacts with the host gastrointestinal (GI) tract and modulates epithelial cell differentiation and immune system maturation. Escherichia coli is one of the first bacteria colonizing the GI tract of mammals and humans within a few days after birth and become the predominant facultative anaerobic bacteria in the adult microbiota. Certain commensal E. coli are able to induce DNA damage in eukaryotic cells. Genotoxicity of such E. coli strains is known to result from Colibactin synthesis, an hybrid peptide polyketide product able to induce DNA double strand breaks in enterocytes. The biosynthesis pathway of Colibactin is encoded by a genomic island called pks. Several recent epidemiologic studies showed that more thirty per cent of three days old infants are colonized by E. coli pks+. To analyze the long-term effects of colonization early in life by genotoxic E. coli strains, we developed an animal model that mimics the natural transmission of E. coli from the mother' to the neonate through direct contact with the maternal microbiota. Pregnant WISTAR rats were fed with a human genotoxic wild-type commensal E. coli (E. coli WT), an isogenic non-genotoxic mutant (E. coli DeltaclbA), or an isogenic complemented mutant (E. coli DeltaclbA+clbA) for which genotoxicity was restored. After delivery, pups' colonization and DNA-damages in enterocytes were monitored during 100 days. In addition, we analyzed gut development and maturation over the same period. E. coli strains, producing or not Colibactin, were transmitted to the offspring and stably colonized the gut. DNA double strand breaks (DSBs) were observed in enterocytes of newborn rats colonized by E. coli WT or E. coli DeltaclbA+clbA complemented strain but were absent in newborn rats colonized by E. coli DeltaclbA mutant. Interestingly, such genotoxicity was not detected in adults but a mitotic cells pool present signs of DSBs' persistence: with an an increased in number of anaphasic bridges was observed unin adult animals colonized since birth by genotoxic strains. In adult animals, tThe numbers of proliferating and apoptotic cells along were also significantly increased in the intestinal crypts of rats exposed to genotoxic E. coli strains as compared to non-genotoxic E. coli DeltaclbA mutant and this was correlated with an increase of intestinal epithelial cells migration along the crypt-villus axis in rats colonized with the genotoxic E. coli strains. MoreoverIn addition, the numbers of enteéroendocrines cells and Paneth cells were increased in small intestine of the same animals. Finally, ex-vivo analysis of the intestinal barrier using Ussing chambers demonstrated that paracellular permeability to 4kDa dextran-FITC flux was increased in rats colonized by the genotoxic E. coli strains as compared to rats colonized by the isogenic non-genotoxic DeltaclbA mutant. The genotoxicity of commensal E. coli colonizing the newborns has long-lasting consequences on intestinal epithelium integrity, development and maturation at adulthood. These bacteria could be of major concerns since they are increasingly isolated from neonates in Europe and the USA

Transcriptional regulation of ASPA in prostate cancer cells

[EN] Prostate cancer (PCa) is a remarkably widespread disease. The role of modulator peroxisome proliferator-activated receptor gamma co-activator 1α (PGC1α) could be of distinguished relevance for diagnosis and treatment for this type of cancer, as it has been proved to be a tumour suppressor in PCa. PGC1α interacts with the estrogen-related receptor α (ERRα). The complex that is formed induces a metabolic rewiring that reduces proliferation, shrinks PCa’s aggressiveness and eases metastatic stages. The gene ASPA, which codes for aspartoacylase protein, has been shown to be of great interest in PCa patients. Its expression is modified in patients according to preliminary data: ASPA is upregulated under PGC1α’s induction. This study has proven the molecular mechanisms by means of which ASPA is regulated, resulting in the following conclusions: in vitro, ASPA is regulated by PGC1α through ERRα and ERRα itself regulates the expression of ASPA (given deletion of ERRα, ASPA is downregulated). In vivo, at mRNA level, ASPA is downregulated as a result of ERRα knockout, while it is upregulated due to PGC1α’s induction, as well as in vitro; nonetheless, at protein level ASPA follows another expression patron, being it overexpressed in ERRα knockout conditions under PGC1α’s induction. Hence, ASPA could be used as a biomarker for PCa and as a target for future therapies.[ES] El cáncer de próstata (PCa) es una enfermedad notablemente extendida. El papel del modulador del receptor gamma activado por el proliferador de peroxisomas 1α (PGC1α) podría ser de gran relevancia para el diagnóstico y el tratamiento de este tipo de cáncer, ya que se ha demostrado que es un supresor tumoral en el PCa. El PGC1α interactúa con el receptor α relacionado con el estrógeno (ERRα). El complejo que se forma induce un reordenamiento metabólico que reduce la proliferación, disminuye la agresividad del PCa y facilita las fases metastásicas. El gen ASPA, que codifica la proteína aspartoacilasa, ha demostrado ser de gran interés en los pacientes con PCa. Su expresión está modificada en los pacientes, según datos preliminares: ASPA se regula al alza bajo la inducción de PGC1α. En este estudio se han comprobado los mecanismos moleculares mediante los cuales se regula ASPA, llegando a las siguientes conclusiones: in vitro, ASPA es regulado por PGC1α a través de ERRα y el propio ERRα regula la expresión de ASPA (dada la deleción de ERRα, ASPA se regula a la baja). In vivo, a nivel de ARNm, ASPA se regula a la baja como resultado de la supresión de ERRα, mientras que se regula al alza debido a la inducción de PGC1α, así como in vitro; sin embargo, a nivel de proteínas ASPA sigue otro patrón de expresión, siendo sobreexpresado en condiciones de supresión de ERRα bajo la inducción de PGC1α. Por lo tanto, ASPA podría ser utilizado como un biomarcador para el PCa y como un objetivo para futuras terapias

Calcareous nannofossil biostratigraphic analysis of the lower Eocene of the Barinatxe section (Western Pyrenees)

The Barinatxe section (Western Pyrenees) contains one of the most complete and expanded deep-water succession of the early Eocene so far described. The succession, cropped out continuously along sea cliffs, is rich in well preserved calcareous nannofossil. The calcareous nannofossil study carried out in Barinatxe section, where a total of 70 autochthonous early Eocene calcareous nannofossil species have been identified, has allowed us to identify Zones NP10, NP11, NP12 and NP13. Furthermore, we have precisely pinpointed the succession of calcareous nannofossil biohorizons and their relative position within the planktic foraminifer zones. The calcareous nannofossil and planktic foraminifer intercalibration scheme resulted from this study does not agree with the current standard biomagnetochronologic correlation scheme. In order to corroborate or contradict our observations similar studies in sections of a wide range of latitudes and depositional environments are neede

The effects of astronomically forced climate change on hemipelagic carbonate sedimentation in a tectonically active setting: the Albian Mioño Formation in Castro Urdiales (Cantabria, N Spain)

Our understanding of the stratigraphic expression of astronomically driven climate-change cycles in the Milankovitch frequency band has improved significantly in recent decades. However, several aspects have been little studied to date, such as the nature of the climatically regulated environmental processes that ultimately control cyclic sedimentation. Similarly, relatively little is known about the expression of Milankovitch cycles in successions accumulated in tectonically active basins. In order to fill this knowledge gap, the Albian hemipelagic deposits of the Miono Formation exposed in Castro Urdiales (Basque-Cantabrian Basin) are studied herein. These deposits were accumulated during a rifting phase with strong tectonic activity. The sedimentological, petrographic and cyclostratigraphic analysis demonstrates that, despite the synsedimentary tectonic instabilities and some diagenetic overprinting, the hemipelagic carbonate alternation was astronomically forced 110.68-110.47 Ma. Seasonality fluctuations driven by precession cycles caused periodic (20 ky) variations in the rate of carbonate productivity (abundance of pelagic calcareous plankton and micrite exported from adjacent shallow-water areas) and/or siliceous dilution (terrestrially derived siliciclastic sediment supply and siliceous particle production by sponges). These variations resulted in the formation of marly limestone beds when annual seasonality was low (i.e., boreal summer at aphelion, winter at perihelion) and the accumulation of marlstones when seasonality increased (i.e., boreal summer at perihelion, winter at aphelion). The incidence of these processes increased and decreased in line with seasonality modulation by short-eccentricity cycles of 100 ky. In conclusion, this study shows that Milankovitch cycles can be reliably recorded in hemipelagic successions accumulated in tectonically active settings if sediment gravity flows or other disturbances do not affect autochthonous sedimentation.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Research funded by the MCIN/AEI project PID2019-105670GB-I00/AEI/10.13039/501100011033 of the Spanish Government and by the Consolidated Research Group IT160222 of the Basque Government

Systematics of Lutetian larger foraminifera and magneto-biostratigraphy from the South Pyrenean Basin (Sierras Exteriores, Spain)

A systematic description of the Eocene larger foraminifera recorded in the South Pyrenean Basin (Sierras Exteriores) is presented herein. The large dataset provided in this work includes Nummulites and Alveolina species, along with a variety of other porcellaneous and hyaline taxa with lesser biostratigraphic relevance. Most of the larger foraminifera described in this work correspond to the Lutetian (SBZ13 to SBZ16 biozones) interval, but late Ypresian (SBZ11, Cuisian) and early Bartonian (SBZ17) shallow benthic zones have also been identified. A new species, Idalinaosquetaensis, is described. The systematic revision of middle to late Lutetian alveolines led to a reassessment of Alveolinafusiformis and the finding of two new precursor forms, described as Alveolina aff. fragilis and Alveolina aff. elongata. The new taxa fill in the gap existing so far in the middle to late Lutetian alveolinid biostratigraphy. Despite not being exclusive to SBZ16, these forms provide realiable biostratigraphic information in facies where Nummulites are not present. This realibility lies on the correlation of Nummulitesand Alveolina biostratigraphic markers in the same sections and their calibration to the global time scale through magnetostratigraphy. Magnetostratigraphic calibration of described taxa is provided, along with an update of the SBZ calibration to the Geological Time Scale (Gradstein et al., 2012).&nbsp

Environmental effect of astronomical climate change on lower Eocene hemipelagic deposits (Sopelana, Biscay)

Las sucesiones eocenas expuestas en Sopelana (Bizkaia) están caracterizadas por la alternancia de calizas y margas hemipelágicas que se organizan en trece grupos, cada uno con cinco pares caliza-marga. Esta organización sugiere que la formación de los pares estuvo controlada por ciclos astronómicos de precesión (20 ka) y la de los grupos por ciclos de excentricidad (100 ka). Se ha estudiado el contenido en carbonato y los isótopos estables de carbono y oxígeno de los pares del duodécimo grupo, a fin de descifrar los cambios ambientales en medios marinos profundos provocados por los ciclos de precesión y excentricidad y determinar las diferentes configuraciones orbitales que condujeron a la formación de cada capa.The Eocene successions exposed in Sopelana (Biscay) are characterized by the alternation of hemipelagic limestones and marls organized in thirteen distinctive bundles, each of which contains five limestone-marl couplets. Such an arrangement suggests that the formation of the couplets was driven by astronomical precession cycles (20 ky each) and that of the bundles by eccentricity cycles (100 ky). The couplets within the twelfth bundle were analysed for their carbonate content and their oxygen and carbon stable isotopes, with the aim of deciphering accurately the deep-sea environmental changes caused by the precession and eccentricity cycles and the varying orbital configurations that led to the formation of each be

Correlation of the Thanetian-Ilerdian turnover of larger foraminifera and the Initial Eocene thermal maximum (IETM) confirming evidence from the Campo area (Pyrenees, Spain)

Abstrac

Systematics of Lutetian larger foraminifera and magneto-biostratigraphy from the South Pyrenean Basin (Sierras Exteriores, Spain)

An extense systematic description of the Eocene larger foraminiferal faunas recorded in the South Pyrenean Basin (Sierras Exteriores) is presented herein. The large dataset provided in this work includes both Nummulites and Alveolina species, along with a variety of other porcellaneous and hyaline taxa with lesser biostratigraphic relevance, are represented. The larger foraminifera described in this work correspond mainly to the Lutetian (SBZ13 to SBZ16 biozones) interval, but late Ypresian (SBZ11, Cuisian) and Bartonian (SBZ17) shallow benthic zones have also been identified. As one of the most relevant results of this systematic analysis, a new species, Idalina osquetaensis, is described. The systematic revision of middle to late Lutetian alveolines led to a reassessment of A. fusiformis and the finding of two new precursor forms, described as affinis of their corresponding species, A. aff. fragilis and A. aff. elongata. The new forms A. aff. elongata and A. aff. fragilis fill the gap in the middle to late Lutetian alveolinid biostratigraphy. Despite not being exclusive to SBZ16, these new forms provide realiable biostratigraphic information where Nummulites are not present. This realibility lies on the correlation of Nummulites and Alveolina biomarkers in the same sections and their calibration to the global time scale through magnetostratigraphy. In fact, magnetostratigraphic calibration of all described taxa is also provided, along with an update of the SBZ calibration to the current Geologic Time Scale (Gradstein et al., 2012)