114 research outputs found

    Isotope geochemistry and petrogenesis of peralkaline Middle Miocene ignimbrites from central Sonora: relationship with continental break-up and the birth of the Gulf of California

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    Middle Miocene peralkaline ignimbrites constitute a specific geodynamic marker of the early stage of opening of the Gulf of California, preserved either in central Sonora or the Puertecitos area, in Baja California. Very uniform ages (12-12.5 Ma) obtained on these rocks show that this volcanic episode corresponds to a specific stage in the tectonic evolution of the proto-gulf area. Field observations and slightly different Sr and Nd isotopic signatures support eruptions from several small volume magma batches rather than from a large-volume caldera forming event. Isotopic ratios help to constrain the petrogenesis of the peralkaline liquids by fractional crystallization of transitional basalts in a shallow reservoir, with slight contamination by Precambrian upper crustal material. Less differentiated glomeroporphyritic icelandites erupted at about 11 Ma, mark an increase in the magma production rate and highlight an easier access to the surface, illustrating an advanced stage in the weakening of the continental crust. The tilting of the Middle Tertiary sequences results from a major change in the tectonic regime, from E-W extension giving rise to N-S grabens, to NNW-SSE strike-slip motion that can be related to the transfer of Baja California from North America to the Pacific plate. The location of peralkaline volcanism coincides with the southern edge of the Precambrian crust and the southernmost extension of the California slab window at 12.5 Ma

    Morphological variation and different branch modularity across contrasting flow conditions in dominant Pocillopora reef-building corals

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    © 2015, Springer-Verlag Berlin Heidelberg. Pocillopora corals, the dominant reef-builders in the Eastern Tropical Pacific, exhibit a high level of phenotypic plasticity, making the interpretation of morphological variation and the identification of species challenging. To test the hypothesis that different coral morphospecies represent phenotypes that develop in different flow conditions, we compared branch characters in three Pocillopora morphospecies (P.damicornis, P. verrucosa, and P. meandrina) from two communities in the Gulf of California exposed to contrasting flow conditions. Morphological variation and branch modularity (i.e., the tendency of different sets of branch traits to vary in a coordinated way) were assessed in colonies classified as Pocillopora type 1 according to two mitochondrial regions. Our results can be summarized as follows. (1) Pocillopora type 1 morphospecies corresponded to a pattern of morphological variation in the Gulf of California. Overall, P.damicornis had the thinnest branches and its colonies the highest branch density, followed by P.verrucosa, and then by P.meandrina, which had the thickest branches and its colonies the lowest branch density. (2) The differentiation among morphospecies was promoted by different levels of modularity of traits. P.verrucosa had the highest coordination of traits, followed by P.damicornis, and P.meandrina. (3) The variation and modularity of branch traits were related to water flow condition. Morphology under the high-flow condition was more similar among morphospecies than under the low-flow condition and seemed to be related to mechanisms for coping with these conditions. Our results provide the first evidence that in scleractinian corals different levels of modularity can be promoted by different environmental conditions

    Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury.

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    Binge drinking, i.e., heavy episodic drinking in a short time, has recently become an alarming societal problem with negative health impact. However, the harmful effects of acute alcohol injury in the gut-liver axis remain elusive. Hence, we focused on the physiological and pathological changes and the underlying mechanisms of experimental binge drinking in the context of the gut-liver axis. Eight-week-old mice with a C57BL/6 background received a single dose (p.o.) of ethanol (EtOH) [6 g/kg b.w.] as a preclinical model of acute alcohol injury. Controls received a single dose of PBS. Mice were sacrificed 8 h later. In parallel, HepaRGs and Caco-2 cells, human cell lines of differentiated hepatocytes and intestinal epithelial cells intestinal epithelial cells (IECs), respectively, were challenged in the presence or absence of EtOH [0-100 mM]. Extracellular vesicles (EVs) isolated by ultracentrifugation from culture media of IECs were added to hepatocyte cell cultures. Increased intestinal permeability, loss of zonula occludens-1 (ZO-1) and MUCIN-2 expression, and alterations in microbiota-increased Lactobacillus and decreased Lachnospiraceae species-were found in the large intestine of mice exposed to EtOH. Increased TUNEL-positive cells, infiltration of CD11b-positive immune cells, pro-inflammatory cytokines (e.g., tlr4, tnf, il1β), and markers of lipid accumulation (Oil Red O, srbep1) were evident in livers of mice exposed to EtOH, particularly in females. In vitro experiments indicated that EVs released by IECs in response to ethanol exerted a deleterious effect on hepatocyte viability and lipid accumulation. Overall, our data identified a novel mechanism responsible for driving hepatic injury in the gut-liver axis, opening novel avenues for therapy.This work was supported by the MINECO Retos SAF2016-78711, SAF2017-87919-R, EXOHEP-CM S2017/BMD-3727, NanoLiver-CM Y2018/NMT-4949, ERAB Ref. EA 18/14, AMMF 2018/117, UCM-25-2019 and COST Action CA17112, the German Research Foundation (SFB/TRR57/P04, SFB 1382-403224013/A02, and DFG NE 2128/2-1). FC and YN are Ramón y Cajal Researchers RYC-2014-15242 and RYC-2015-17438. FC is a Gilead Liver Research 2018. KZ is a recipient of a Chinese Scholarship Council (CSC). BK20170127 from the Natural Science Foundation of Jiangsu Province to JP.S

    Actividad física, ejercicio y deporte en la lucha contra la obesidad infantil y juvenil

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    El propósito del presente documento es proponer desde el grupo de expertos en ejercicio físico y salud de EXERNET (Red Española de Investigación en Ejercicio Físico y Salud) una serie de recomendaciones sobre la práctica de la actividad física y deportiva que a nivel individual, familiar e institucional ayuden a prevenir y tratar la obesidad infantil y juvenil, basadas en la evidencia científi ca actual

    YES1 drives lung cancer growth and progression and predicts sensitivity to dasatinib

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    Rationale: The characterization of new genetic alterations is essential to assign effective personalized therapies in non–small cell lung cancer (NSCLC). Furthermore, finding stratification biomarkers is essential for successful personalized therapies. Molecular alterations of YES1, a member of the SRC (proto-oncogene tyrosine-protein kinase Src) family kinases (SFKs), can be found in a significant subset of patients with lung cancer. Objectives: To evaluate YES1 (v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1) genetic alteration as a therapeutic target and predictive biomarker of response to dasatinib in NSCLC. Methods: Functional significance was evaluated by in vivo models of NSCLC and metastasis and patient-derived xenografts. The efficacy of pharmacological and genetic (CRISPR [clustered regularly interspaced short palindromic repeats]/Cas9 [CRISPR-associated protein 9]) YES1 abrogation was also evaluated. In vitro functional assays for signaling, survival, and invasion were also performed. The association between YES1 alterations and prognosis was evaluated in clinical samples. Measurements and Main Results: We demonstrated that YES1 is essential for NSCLC carcinogenesis. Furthermore, YES1 overexpression induced metastatic spread in preclinical in vivo models. YES1 genetic depletion by CRISPR/Cas9 technology significantly reduced tumor growth and metastasis. YES1 effects were mainly driven by mTOR (mammalian target of rapamycin) signaling. Interestingly, cell lines and patient-derived xenograft models with YES1 gene amplifications presented a high sensitivity to dasatinib, an SFK inhibitor, pointing out YES1 status as a stratification biomarker for dasatinib response. Moreover, high YES1 protein expression was an independent predictor for poor prognosis in patients with lung cancer. Conclusions: YES1 is a promising therapeutic target in lung cancer. Our results provide support for the clinical evaluation of dasatinib treatment in a selected subset of patients using YES1 status as predictive biomarker for therapy

    Bone metabolism and inflammatory biomarkers in radiographic and non-radiographic axial spondyloarthritis patients: a comprehensive evaluation

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    IntroductionAxial spondyloarthritis (axSpA) is a heterogeneous disease that can be represented by radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA). This study aimed to evaluate the relationship between the markers of inflammation and bone turnover in r-axSpA patients and nr-axSpA patients.MethodsA cross-sectional study included 29 r-axSpA patients, 10 nr-axSpA patients, and 20 controls matched for age and sex. Plasma markers related to bone remodeling such as human procollagen type 1 N-terminal propeptide (P1NP), sclerostin, tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) were measured by an ELISA kit. A panel of 92 inflammatory molecules was analyzed by proximity extension assay.ResultsR-axSpA patients had decreased plasma levels of P1NP, a marker of bone formation, compared to controls. In addition, r-axSpA patients exhibited decreased plasma levels of sclerostin, an anti-anabolic bone hormone, which would not explain the co-existence of decreased plasma P1NP concentration; however, sclerostin levels could also be influenced by inflammatory processes. Plasma markers of osteoclast activity were similar in all groups. Regarding inflammation-related molecules, nr-axSpA patients showed increased levels of serum interleukin 13 (IL13) as compared with both r-axSpA patients and controls, which may participate in the prevention of inflammation. On the other hand, r-axSpA patients had higher levels of pro-inflammatory molecules compared to controls (i.e., IL6, Oncostatin M, and TNF receptor superfamily member 9). Correlation analysis showed that sclerostin was inversely associated with IL6 and Oncostatin M among others.ConclusionAltogether, different inflammatory profiles may play a role in the development of the skeletal features in axSpA patients particularly related to decreased bone formation. The relationship between sclerostin and inflammation and the protective actions of IL13 could be of relevance in the axSpA pathology, which is a topic for further investigation

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Staging Parkinson’s Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life

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    COPPADIS Study Group.[Introduction] In a degenerative disorder such as Parkinson’s disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr’s motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient’s quality of life (QoL) with regard to a defined clinical stage.[Materials and Methods] Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0–20; B: NMSS = 21–40; C: NMSS = 41–70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale.[Results] A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; ).[Conclusion] The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden.Peer reviewe
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