A gigantic new dinosaur from Argentina and the evolution of the sauropod hind foot

Titanosauria is an exceptionally diverse, globally-distributed clade of sauropod dinosaurs that includes the largest known land animals. Knowledge of titanosaurian pedal structure is critical to understanding the stance and locomotion of these enormous herbivores and, by extension, gigantic terrestrial vertebrates as a whole. However, completely preserved pedes are extremely rare among Titanosauria, especially as regards the truly giant members of the group. Here we describe Notocolossus gonzalezparejasi gen. et sp. nov. from the Upper Cretaceous of Mendoza Province, Argentina. With a powerfully-constructed humerus 1.76m in length, Notocolossus is one of the largest known dinosaurs. Furthermore, the complete pes of the new taxon exhibits a strikingly compact, homogeneous metatarsus - seemingly adapted for bearing extraordinary weight - and truncated unguals, morphologies that are otherwise unknown in Sauropoda. The pes underwent a near-progressive reduction in the number of phalanges along the line to derived titanosaurs, eventually resulting in the reduced hind foot of these sauropods.Fil: Gonzalez Riga, Bernardo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Laboratorio de Dinosaurios.; ArgentinaFil: Lamanna, Matthew C.. University of Pittsburgh at Johnstown; Estados UnidosFil: Ortiz David, Leonardo Daniel. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Laboratorio de Dinosaurios.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Calvo, Jorge Orlando. Universidad Nacional del Comahue; ArgentinaFil: Coria, Juan Pedro. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Laboratorio de Dinosaurios.; Argentin

Rapid changes in meridional advection of Southern Ocean intermediate waters to the tropical Pacific during the last 30 kyr

The Southern Ocean is increasingly recognized as a key player in the general ocean thermohaline circulation and the global climate system during glacial–interglacial transitions. In particular, the advection of Southern Ocean intermediate waters (SOIW), like Antarctic Intermediate Water and Sub-Antarctic Mode Water, to the Eastern Equatorial Pacific (EEP), through a so-called “oceanic tunnelling” mechanism, is an important means for rapid transfer of climatic signals (such as heat, fresh water, salt, and chemical species) from high-to-low latitudes. However, information on how intermediate water advection rates changed in the past, and particularly during deglaciations, is fragmentary. We present new results for Nd isotopes (εNd) in cleaned foraminifera shells (Neogloboquadrina dutertrei) for the last 30 kyr at ODP Site 1240 in the EEP. N. dutertrei preferentially dwells in the lower thermocline, at the core of the Equatorial Undercurrent (EUC), and the εNd variability over time provides a record of the changes in the εNd of the EUC. Through mixing models we show that the EUC record is primarily controlled by changes in the volume transport of intermediate waters and not by Southern Ocean εNd changes. Southern Ocean signals in the EUC are stronger during colder intervals (Younger Dryas, last glacial maximum and Heinrich stadials 1 and 2), in agreement with tropical Atlantic intermediate water records. In addition, covariations between N. dutertrei δ13C, molecular biomarkers, and diatom productivity at Site 1240 confirm the intermediate water route as an important mechanism for the transfer of climate signals from high-to-low latitudes. Changes in the SOIW chemistry during the deglaciation are likely linked to the upwelling of ‘old’ deep waters in the Southern Ocean and subsequent export as intermediate waters, which are coeval with the atmospheric CO2 rise. Moreover, a comparison of multiple proxy records for the last 30 kyr indicates a latitudinal shift and/or a change in the convection depth of intermediate waters in the Southern Ocean prior to the onset of the deglaciation

KELT-17: a chemically peculiar Am star and a hot-Jupiter planet

Context. The detection of planets orbiting chemically peculiar stars is very scarcely known in the literature. Aims. To determine the detailed chemical composition of the remarkable planet host star KELT-17. This object hosts a hot-Jupiter planet with 1.31 MJup detected by transits, being one of the more massive and rapidly rotating planet hosts to date. We aimed to derive a complete chemical pattern for this star, in order to compare it with those of chemically peculiar stars. Methods. We carried out a detailed abundance determination in the planet host star KELT-17 via spectral synthesis. Stellar parameters were estimated iteratively by fitting Balmer line profiles and imposing the Fe ionization balance, using the program SYNTHE together with plane-parallel ATLAS12 model atmospheres. Specific opacities for an arbitrary composition and microturbulence velocity vmicro were calculated through the Opacity Sampling (OS) method. The abundances were determined iteratively by fitting synthetic spectra to metallic lines of 16 different chemical species using the program SYNTHE. The complete chemical pattern of KELT-17 was compared to the recently published average pattern of Am stars. We estimated the stellar radius by two methods: a) comparing the synthetic spectral energy distribution with the available photometric data and the Gaia parallax, and b) using a Bayesian estimation of stellar parameters using stellar isochrones. Results. We found overabundances of Ti, Cr, Mn, Fe, Ni, Zn, Sr, Y, Zr, and Ba, together with subsolar values of Ca and Sc. Notably, the chemical pattern agrees with those recently published of Am stars, being then KELT-17 the first exoplanet host whose complete chemical pattern is unambiguously identified with this class. The stellar radius derived by two different methods agrees to each other and with those previously obtained in the literature.Comment: 5 pages, 8 figures, 2 tables, A&A accepte

Effect of topical berberine in murine cutaneous leishmaniasis lesions

Objectives: More effective topical treatments remain an unmet need for the localized forms of cutaneous leishmaniasis (CL). The aim of this study was to evaluate the efficacy and safety of a topical berberine cream in BALB/c mice infected with Leishmania major parasites. Methods: A cream containing 0.5% berberine-β-glycerophosphate salt and 2.5% menthol was prepared. Its physicochemical and stability properties were determined. The cream was evaluated for its capacity to reduce lesion size and parasitic load as well as to promote wound healing after twice-a-day administration for 35 days. Clinical biochemical profile was used for estimating off-target effects. In vitro time-to-kill curves in L. major-infected macrophages and skin and plasma pharmacokinetics were determined, aiming to establish pharmacokinetic/pharmacodynamic relationships. Results: The cream was stable at 40°C for 3 months and at 4°C for at least 8 months. It was able to halt lesion progression in all treated mice. At the end of treatment, parasite load in the skin was reduced by 99.9% (4 log) and genes involved in the wound healing process were up-regulated compared with untreated mice. The observed effects were higher than expected from in vitro time-to-kill kinetic and plasma berberine concentrations, which ranged between 0.07 and 0.22 μM. Conclusions: The twice-a-day administration of a topical berberine cream was safe, able to stop parasite progression and improved the appearance of skin CL lesions. The relationship between drug plasma levels and in vivo effect was unclear

Matrix metalloproteinase-10 is upregulated by thrombin in endothelial cells and increased in patients with enhanced thrombin generation

OBJECTIVE: Thrombin is a multifunctional serine protease that promotes vascular proinflammatory responses whose effect on endothelial MMP-10 expression has not previously been evaluated. METHODS AND RESULTS: Thrombin induced endothelial MMP-10 mRNA and protein levels, through a protease-activated receptor-1 (PAR-1)-dependent mechanism, in a dose- and time-dependent manner. This effect was mimicked by a PAR-1 agonist peptide (TRAP-1) and antagonized by an anti-PAR-1 blocking antibody. MMP-10 induction was dependent on extracellular regulated kinase1/2 (ERK1/2) and c-jun N-terminal kinase (JNK) pathways. By serial deletion analysis, site-directed mutagenesis and electrophoretic mobility shift assay an AP-1 site in the proximal region of MMP-10 promoter was found to be critical for thrombin-induced MMP-10 transcriptional activity. Thrombin and TRAP-1 upregulated MMP-10 in murine endothelial cells in culture and in vivo in mouse aorta. This effect of thrombin was not observed in PAR-1-deficient mice. Interestingly, circulating MMP-10 levels (P<0.01) were augmented in patients with endothelial activation associated with high (disseminated intravascular coagulation) and moderate (previous acute myocardial infarction) systemic thrombin generation. CONCLUSIONS: Thrombin induces MMP-10 through a PAR-1-dependent mechanism mediated by ERK1/2, JNK, and AP-1 activation. Endothelial MMP-10 upregulation could be regarded as a new proinflammatory effect of thrombin whose pathological consequences in thrombin-related disorders and plaque stability deserve further investigation

Imaging neutron capture cross sections: i-TED proof-of-concept and future prospects based on Machine-Learning techniques

Babiano-Suárez, V., et al.i-TED is an innovative detection system which exploits Compton imaging techniques to achieve a superior signal-to-background ratio in (n, γ) cross-section measurements using time-of-flight technique. This work presents the first experimental validation of the i-TED apparatus for high-resolution time-of-flight experiments and demonstrates for the first time the concept proposed for background rejection. To this aim, the Au(n, γ) and Fe(n, γ) reactions were studied at CERN n_TOF using an i-TED demonstrator based on three position-sensitive detectors. Two CD detectors were also used to benchmark the performance of i-TED. The i-TED prototype built for this study shows a factor of ∼ 3 higher detection sensitivity than state-of-the-art CD detectors in the 10 keV neutron-energy region of astrophysical interest. This paper explores also the perspectives of further enhancement in performance attainable with the final i-TED array consisting of twenty position-sensitive detectors and new analysis methodologies based on Machine-Learning techniques.This work has been carried out in the framework of a project funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC Consolidator Grant project HYMNS, with grant agreement No. 681740). The authors acknowledge support from the Spanish Ministerio de Ciencia e Innovación under grants PID2019-104714GB-C21, FPA2017-83946-C2-1-P, FIS2015-71688-ERC, CSIC for funding PIE-201750I26, and the funding agencies of the participating institutes. We would like to thank the crew at the Electronics Laboratory of IFIC, in particular Manuel Lopez Redondo and Jorge Nácher Arándiga for their excellent and efficient work

Global Governance Behind Closed Doors : The IMF Boardroom, the Enhanced Structural Adjustment Facility, and the Intersection of Material Power and Norm Change in Global Politics

Up on the 12th floor of its 19th Street Headquarters, the IMF Board sits in active session for an average of 7 hours per week. Although key matters of policy are decided on in the venue, the rules governing Boardroom interactions remain opaque, resting on an uneasy combination of consensual decision-making and weighted voting. Through a detailed analysis of IMF Board discussions surrounding the Enhanced Structural Adjustment Facility (ESAF), this article sheds light on the mechanics of power in this often overlooked venue of global economic governance. By exploring the key issues of default liability and loan conditionality, I demonstrate that whilst the Boardroom is a more active site of contestation than has hitherto been recognized, material power is a prime determinant of both Executive Directors’ preferences and outcomes reached from discussions. And as the decisions reached form the backbone of the ‘instruction sheet’ used by Fund staff to guide their everyday operational decisions, these outcomes—and the processes through which they were reached—were factors of primary importance in stabilizing the operational norms at the heart of a controversial phase in the contemporary history of IMF concessional lending

Influence of high cardiovascular risk in asymptomatic people on the duration and cost of sick leave: results of the ICARIA study.

AIMS: We investigated the potential influence of a moderate-to-high cardiovascular (CV) risk (CVR) (defined as a Systematic COronary Risk Evaluation model, or SCORE ≥ 4%), in the absence of an established CV disease, on the duration and cost of CV and non-CV sick leave (SL) resulting from common and occupational accidents or diseases. METHODS AND RESULTS: We conducted a prospective cohort study on 690 135 workers with a 1-year follow-up and examined CV- and non-CV-related SL episodes. To obtain baseline values, CVR factors were initially assessed at the beginning of the year during routine medical examination. The CVR was calculated with the SCORE charts for all subjects. Moderate-to-high CVR was defined as SCORE ≥ 4%. A baseline SCORE ≥ 4% was associated with a higher risk for long-term CV and non-CV SL, as revealed by follow-up assessment. This translated into an increased cost, estimated at euro5 801 464.18 per year. Furthermore, pharmacological treatment for hypertension or hyperlipidaemia was significantly associated with longer SL duration. CONCLUSION: Moderate-to-high CVR in asymptomatic subjects was significantly associated with the duration and cost of CV and non-CV SL. These results constitute the first body of evidence that the SCORE charts can be used to identify people with a non-established CV disease, which might ultimately translate into more lost workdays and therefore increased cost for society

Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell