Chronostratigraphy of the Barremian-Early Albian of the Maestrat Basin (E Iberian Peninsula): integrating strontium-isotope stratigraphy and ammonoid biostratigraphy

A revised chronostratigraphy of the Barremian - Early Albian sedimentary record of the Maestrat Basin (E Iberian Peninsula) is provided based on a comprehensive synthesis of previous biostratigrahic data, a new ammonoid finding and numerical ages derived from 87Sr/86Sr values measured on shells of rudists, oysters and brachiopods. The succession, which comprises eight lithostratigraphic formations, is arranged into six major transgressive-regressive sequences and plotted against numerical ages, geomagnetic polarity chrons, ammonoid zones and the stratigraphic distribution of age-diagnostic ammonoids, orbitolinid fora- minifera and rudist bivalves. The oldest lithostratigraphic unit sampled, the marine Artoles Formation, is Early to Late Barremian. Above, the dinosaur-bearing deposits of the Morella Formation and its coastal to shallow-marine equivalent, the Cervera del Maestrat Formation, are of Late Barremian age and span at least part of the Imerites giraudi ammonoid zone. 87Sr/ 86Sr ratios from oyster shells in the upper part of the overlying marine Xert Formation are consistent with a latest Barremian-earliest Aptian age, while an ammonite belonging to the Late Barremian Martelites sarasini Zone was collected within the lowermost part of this lat- ter formation. The Barremian-Aptian boundary is tentatively placed close above the base of the succeeding transgressive marls of the Forcall Formation by analogy with nearby Tethyan basins, where major transgres- sive records contain latest Barremian ammonoids in their basal parts. The rest of the Forcall Formation and the platform carbonates of the Villarroya de los Pinares Formation are of Early Aptian age. The transition from the Barremian into the Aptian occurred in the course of a wide transgression, which was accompanied by the proliferation of Palorbitolina lenticularis. This transgressive event drowned Late Barremian carbonate platforms (Xert Formation) throughout the basin. Extensive carbonate platforms (Villarroya de los Pinares Formation) recovered coevally with a post-OAE 1a late Early Aptian major regression of relative sea level. The last lithostratigraphic unit analyzed, the marine Benassal Formation, spans the terminal Early Aptian- Late Aptian interval. Based on ammonite distributions, the lower part of the overlying coastal to continental coal-bearing Escucha Formation is Early Albian in age. This improved chronostratigraphic knowledge allows a more precise correlation of the sedimentary record studied with other coeval successions worldwide

Calcite/aragonite ratio fluctuations in Aptian rudist bivalves: Correlation with changing temperatures

Understanding how bivalves responded to past temperature fluctuations may help us to predict specific responses of complex calcifiers to future climate change. During the late-Early Aptian, aragonite-rich rudist bivalves decreased in abundance in northern Tethyan carbonate platforms, while rudists with a thickened calcitic outer shell layer came to dominate those of Iberia. Seawater cooling and variations in calcium carbonate saturation states may have controlled this faunal turnover. However, our understanding of how rudist lineages responded to changing environmental conditions is constrained by a lack of quantitative data on the evolution of thickness, size, and mineralogy of the shell. This study is based on volumetric measurements of the shell and shows the transition in lineages of the family Polyconitidae from aragonite-rich mineralogy in the earliest Aptian, to low-Mg calcite-dominated mineralogy in the middle Aptian, returning to aragonite-dominated composition in the latest Aptian. The platform biocalcification crisis that occurred at the Early-Late Aptian boundary in the Tethys was marked by a relative increase of calcite and a decrease in skeletal thickness and commissural diameters. The highest calcite/aragonite (Cc/A) ratios in polyconitid rudists accompanied the late Aptian cold episode, and the lowest values were reached during the warmer intervals of the earliest and latest Aptian. These results imply a correlation between Cc/A ratio values and temperature and suggest that some bivalves adapted to less favorable calcification conditions by changing calcite and aragonite proportions of their bimineralic shells and decreasing skeletal thickness, thereby reducing the metabolic cost of shell growth. GeoRef Subjec

Cerium oxide nanoparticles regulate insulin sensitivity and oxidative markers in 3T3-L1 adipocytes and C2C12 myotubes

Insulin resistance is associated with oxidative stress, mitochondrial dysfunction, and a chronic low-grade inflammatory status. In this sense, cerium oxide nanoparticles (CeO2 NPs) are promising nanomaterials with antioxidant and anti-inflammatory properties. Thus, we aimed to evaluate the effect of CeO2 NPs in mouse 3T3-L1 adipocytes, RAW 264.7 macrophages, and C2C12 myotubes under control or proinflammatory conditions. Macrophages were treated with LPS, and both adipocytes and myotubes with conditioned medium (25% LPS-activated macrophages medium) to promote inflammation. CeO2 NPs showed a mean size of ≤25.3 nm (96.7%) and a zeta potential of mV, suitable for cell internalization. CeO2 NPs reduced extracellular reactive oxygen species (ROS) in adipocytes with inflammation while increased in myotubes with control medium. The CeO2 NPs increased mitochondrial content was observed in adipocytes under proinflammatory conditions. Furthermore, the expression of Adipoq and Il10 increased in adipocytes treated with CeO2 NPs. In myotubes, both Il1b and Adipoq were downregulated while Irs1 was upregulated. Overall, our results suggest that CeO2 NPs could potentially have an insulin-sensitizing effect specifically on adipose tissue and skeletal muscle. However, further research is needed to confirm these findings

Neoadjuvant eribulin in HER2-negative early-stage breast cancer (SOLTI-1007-NeoEribulin): a multicenter, two-cohort, non-randomized phase II trial

Breast cancer; Predictive markers; Translational researchCáncer de mama; Maradores predictivos; Investigación traslacionalCàncer de mama; Marcadors predictius; Recerca translacionalEribulin prolongs overall survival in patients with pre-treated advanced breast cancer. However, no biomarker exists to prospectively select patients who will benefit the most from this drug. SOLTI-1007-NeoEribulin is a phase II, open-label, two-cohort, exploratory pharmacogenomic study in patients with clinical stage I–II HER2-negative breast cancer receiving neoadjuvant eribulin monotherapy treatment. Primary objective was to explore the association of baseline tumor gene expression with pathological complete response in the breast (pCRB) at surgery. Key secondary objectives were pCRB rates in all patients and according to HR status, gene expression changes during treatment and safety. One-hundred one hormonal receptor-positive (HR + ) and seventy-three triple-negative breast cancer (TNBC) patients were recruited. The pCRB rates were 6.4% in all patients, 4.9% in HR + disease and 8.2% in TNBC. The TNBC cohort was interrupted due to a progression disease rate of 30.1%. The pCRB rates differed according to intrinsic subtypes: 28.6% in HER2-enriched, 11.1% in Normal-like, 7.9% in Luminal B, 5.9% in Basal-like and 0% in Luminal A (HER2-enriched vs. others odds ratio = 7.05, 95% CI 1.80–42.14; p-value = 0.032). Intrinsic subtype changes at surgery occurred in 33.3% of cases, mostly (49.0%) Luminal B converting to Luminal A or Basal-like converting to Normal-like. Baseline tumor-infiltrating lymphocytes (TILs) were significantly associated with pCR. Eribulin showed a good safety profile with a low response and pCRB rates. Patients with HER2-negative disease with a HER2-enriched profile may benefit the most from eribulin. In addition, significant biological activity of eribulin is observed in Luminal B and Basal-like subtypes

Capacity of countries to reduce biological invasions

The extent and impacts of biological invasions on biodiversity are largely shaped by an array of socio-economic and environmental factors, which exhibit high variation among countries. Yet, a global analysis of how these factors vary across countries is currently lacking. Here, we investigate how five broad, country-specific socio-economic and environmental indices (Governance, Trade, Environmental Performance, Lifestyle and Education, Innovation) explain country-level (1) established alien species (EAS) richness of eight taxonomic groups, and (2) proactive or reactive capacity to prevent and manage biological invasions and their impacts. These indices underpin many aspects of the invasion process, including the introduction, establishment, spread and management of alien species. They are also general enough to enable a global comparison across countries, and are therefore essential for defining future scenarios for biological invasions. Models including Trade, Governance, Lifestyle and Education, or a combination of these, best explained EAS richness across taxonomic groups and national proactive or reactive capacity. Historical (1996 or averaged over 1996–2015) levels of Governance and Trade better explained both EAS richness and the capacity of countries to manage invasions than more recent (2015) levels, revealing a historical legacy with important implications for the future of biological invasions. Using Governance and Trade to define a two-dimensional socio-economic space in which the position of a country captures its capacity to address issues of biological invasions, we identified four main clusters of countries in 2015. Most countries had an increase in Trade over the past 25 years, but trajectories were more geographically heterogeneous for Governance. Declines in levels of Governance are concerning as they may be responsible for larger levels of invasions in the future. By identifying the factors influencing EAS richness and the regions most susceptible to changes in these factors, our results provide novel insights to integrate biological invasions into scenarios of biodiversity change to better inform decision-making for policy and the management of biological invasions

KAP Degradation by Calpain Is Associated with CK2 Phosphorylation and Provides a Novel Mechanism for Cyclosporine A-Induced Proximal Tubule Injury

The use of cyclosporine A (CsA) is limited by its severe nephrotoxicity that includes reversible vasoconstrictor effects and proximal tubule cell injury, the latter associated whith chronic kidney disease progression. The mechanisms of CsA-induced tubular injury, mainly on the S3 segment, have not been completely elucidated. Kidney androgen-regulated protein (KAP) is exclusively expressed in kidney proximal tubule cells, interacts with the CsA-binding protein cyclophilin B and its expression diminishes in kidneys of CsA-treated mice. Since we reported that KAP protects against CsA toxicity in cultured proximal tubule cells, we hypothesized that low KAP levels found in kidneys of CsA-treated mice might correlate with proximal tubule cell injury. To test this hypothesis, we used KAP Tg mice developed in our laboratory and showed that these mice are more resistant to CsA-induced tubular injury than control littermates. Furthermore, we found that calpain, which was activated by CsA in cell cultures and kidney, is involved in KAP degradation and observed that phosphorylation of serine and threonine residues found in KAP PEST sequences by protein kinase CK2 enhances KAP degradation by calpain. Moreover, we also observed that CK2 inhibition protected against CsA-induced cytotoxicity. These findings point to a novel mechanism for CsA-induced kidney toxicity that might be useful in developing therapeutic strategies aimed at preventing tubular cell damage while maintaining the immunosuppressive effects of CsA

Mediterranean bioconstructions along the Italian coast

Marine bioconstructions are biodiversity-rich, three-dimensional biogenic structures, regulating key ecological functions of benthic ecosystems worldwide. Tropical coral reefs are outstanding for their beauty, diversity and complexity, but analogous types of bioconstructions are also present in temperate seas. The main bioconstructions in the Mediterranean Sea are represented by coralligenous formations, vermetid reefs, deep-sea cold-water corals, Lithophyllum byssoides trottoirs, coral banks formed by the shallow-water corals Cladocora caespitosa or Astroides calycularis, and sabellariid or serpulid worm reefs. Bioconstructions change the morphological and chemicophysical features of primary substrates and create new habitats for a large variety of organisms, playing pivotal roles in ecosystem functioning. In spite of their importance, Mediterranean bioconstructions have not received the same attention that tropical coral reefs have, and the knowledge of their biology, ecology and distribution is still fragmentary. All existing data about the spatial distribution of Italian bioconstructions have been collected, together with information about their growth patterns, dynamics and connectivity. The degradation of these habitats as a consequence of anthropogenic pressures (pollution, organic enrichment, fishery, coastal development, direct physical disturbance), climate change and the spread of invasive species was also investigated. The study of bioconstructions requires a holistic approach leading to a better understanding of their ecology and the application of more insightful management and conservation measures at basin scale, within ecologically coherent units based on connectivity: the cells of ecosystem functioning

Ecophenotypic variation in the rudist bivalve Polyconites hadriani on an Aptian platform-slope facies gradient from the western Maestrat Basin, eastern Iberia

A morphometric analysis has been carried out on 140 specimens of the polyconitid rudist, Polyconites hadriani Skelton et al. from the Aptian carbonate platforms of the western Maestrat Basin, eastern Iberia, in order to compare the shapes of shells from platform-top to uppermost slope (pl) facies with those from nearby slope (sl) depos-its. Comparisons between shells from these two palaeoenvironmental settings yielded the following results: (1) sl shells reached significantly larger sizes than pl shells (using commissural diameters as proxies for size), while no significant differences were found between the commissural diameters of lower and upper Aptian sl specimens; (2) relative growth of the dorso-ventral, and antero-posterior commissural diameters did not deviate significantly from isometry in either setting; (3) but in pl shells, radial growth of the attached valve’s ventral margin was positively allometric relative both to commis-sural size and to radial growth of the dorsal margin, which had the effect of causing the commissural plane to tilt upwards ventrally during growth, in the manner of flat oys-ters; and (4) in sl shells, by contrast, radial growth of the ventral margin relative to the other variates did not deviate significantly from isometry, so the commissure was evenly raised during growth – with the exception of some crowded specimens, which did show some upward tilting of the ventral margin. These subtle differences of shell shape aris-ing between coeval and contiguous populations are interpreted to reflect ecophenotypic variation in a single species resulting from adaptive plasticity of growth in response to differing conditions in the two settings. Although previous morphometric studies of other rudist taxa have focused on identifying intraspecific variation, most notably in relation to phyletic size increase, this is the first to apply the approach specifically to the recognition of ecophenotypic variation in a rudist species. A critical eye thus needs to be cast over the huge historical legacy of rudist ‘species’ arbitrarily distinguished on typological criteria.Some of the specimens used in this study were collected and measured by Manuel Ortega Facerias for his master’s degree project and Dr Mukerrem Fenerci-Masse is thanked for earlier discussions of the statistical treatment of the morphometric data. We also thank Andrew Johnson and Robert Scott for their detailed and constructive comments on a previous draft of the paper, which greatly helped to improve it. Funding by the Grup de Recerca Reconegut per la Generalitat de Catalunya 2017 SGR 824 ‘Geologia Sedimentària’ and the I + D + i research project PID2020-113912GB-I00 of the Ministerio de Ciencia e Innovación (MICINN) is appreciated