The Farallon-Aluk ridge collision with South America: Implications for the geochemical changes of slab window magmas from fore- to back-arc

The collision of a divergent ocean ridge may evolve into two end cases: in the continuity of ocean-floor subduction, or in the detachment of the subducted plate. The northern Patagonia active plate margin has the unique situation that in Cenozoic time it has been subjected to two divergent ridge collisions, each one representing one of the end members. The Neogene Antarctica-Nazca divergent ridge collision evolved as a continuous ocean-floor subduction system, promoting a magmatic hiatus at the arc axis, the obduction of part of the ridge ocean-floor in the fore-arc, and basaltic volcanism in the back-arc. In contrast, the Paleogene Farallon-Aluk divergent ridge collision evolved into a transform margin, with the detachment and sinking of the Aluk plate and the development of a large slab window. As in the previous case, this collision promoted a magmatic hiatus at the arc axis, but the tectono-magmatic scenario changed to postorogenic synextensional volcanism that spread to the former fore-arc (basalt, andesite, rhyolite) and former back-arc (bimodal ignimbrite flare-up, basalt). Geochemistry of this slab window synextensional volcanism shows more MORB-like basalts towards the former fore-arc, and MORB-OIB-like basalts towards the former back-arc. Instead, an isolated undeformable crustal block in the former back-arc, with an "epeirogenic" response to the slab window and extensional regime, was covered by OIB-type basalts after uplift. Major elements show that slab window basalts reach TiO2 values up to 3 wt%, as compared with the top value of 1.5 wt% of arc magmas. Besides, the MgO with respect to (FeOt + Al2O3) ratio helps to distinguish slab window magma changes from the former fore-arc to the former back-arc and also with respect to the "epeirogenic" block. Higher contents of HFS elements such as Nb and Ta also help to distinguish this slab window from arc magmas and also, to distinguish slab window magma changes from the former fore-arc to the former back-arc and "epeirogenic" block settings. The isotope compositions of slab window magmatism show a disparate coeval array from MORB to crustal sources, interpreted as a consequence of the lack of protracted storage and homogenization due to the extensional setting.Facultad de Ciencias Naturales y Muse

Prostate tumor overexpressed-1 (PTOV1) promotes docetaxel- resistance and survival of castration resistant prostate cancer cells

Metastatic prostate cancer is presently incurable. The oncogenic protein PTOV1, first described in prostate cancer, was reported as overexpressed and significantly correlated with poor survival in numerous tumors. Here, we investigated the role of PTOV1 in prostate cancer survival to docetaxel and self-renewal ability. Transduction of PTOV1 in docetaxel-sensitive Du145 and PC3 cells significantly increased cell survival after docetaxel exposure and induced docetaxel-resistance genes expression (ABCB1, CCNG2 and TUBB2B). In addition, PTOV1 induced prostatospheres formation and self-renewal genes expression (ALDH1A1, LIN28A, MYC and NANOG). In contrast, Du145 and PC3 cells knockdown for PTOV1 significantly accumulated in the G2/M phase, presented a concomitant increased subG1 peak, and cell death by apoptosis. These effects were enhanced in docetaxel-resistant cells. Analyses of tumor datasets show that PTOV1 expression significantly correlated with prostate tumor grade, drug resistance (CCNG2) and self-renewal (ALDH1A1, MYC) markers. These genes are concurrently overexpressed in most metastatic lesions. Metastases also show PTOV1 genomic amplification in significant co-occurrence with docetaxel-resistance and self-renewal genes. Our findings identify PTOV1 as a promoter of docetaxel-resistance and self-renewal characteristics for castration resistant prostate cancer. The concomitant increased expression of PTOV1, ALDH1A1 and CCNG2 in primary tumors, may predict metastasis and bad prognosis

Inventario de localidades con evidencias de paleosuperficies en Paraguay

El geopatrimonio de Paraguay es muy variado, tiene un gran valor científico y en muchos casos estético, constituyéndose así en un recurso susceptible de ser aprovechado mediante el uso turístico/recreativo. Una parte importante de este capital geológico está compuesto por afloramientos rocosos que se corresponden con superficies antiguas, labradas por la erosión en distintos lapsos pre-terciarios (King, 1956). El presente trabajo incluye un inventario, simplificado en cuanto a lo descriptivo, de los sitios dentro del territorio paraguayo, en donde se ha constatado con mayor o menor certeza, la exposición superficial de estas paleosuperficies.Facultad de Ciencias Naturales y Muse

Conducting Polymers Films Deposited on Carbon Steel and Their Interaction with Crude Oil

The formation of scale/solids deposits inside the pipelines is a frequent problem in the petrochemical industry. These scales can be organic as the asphaltenes and inorganic as the accumulations of salts, which apart from blocking the inside of the pipes can also cause a change in the integrity of the steel. Therefore, it is necessary to avoid the conditions where deposition occurs, together with chemical and mechanical methods of remediation to mitigate the deposition. In this work we intend to use conductive polymers in order to inhibit the deposition of asphaltenes on carbon steel surfaces, by using polypyrrole (PPy) as material capable of conducting electrical current. The electrodeposition of PPy on carbon steel were performed by cyclic voltammetry (CV) and chronoamperometry (CA). The results showed that under certain experimental conditions it is possible to make a PPy film with adequate characteristics. Important factors were the grip and electrochemical stability of the formed film on steel, which depends on the electrosynthesis technique and in some cases favoured by a pre-treatment with a 10% HNO3 solution applied to the steel prior to electropolymerization. The PPy films deposited with pre-treatment completely covered the steel surface and showed better stability, adherence and generated a hydrophobic material

Energy-dense diets increase FGF23, lead to phosphorus retention and promote vascular calcifications in rats

Rats with normal renal function (Experiment 1, n = 12) and uninephrectomized (1/2Nx) rats (Experiment 2, n = 12) were fed diets with normal P (NP) and either normal (NF) or high fat (HF). Rats with intact renal function (Experiment 3, n = 12) were also fed NF or HF diets with high P (HP). Additionally, uremic (5/6Nx) rats (n = 16) were fed HP diets with NF or HF. Feeding the HF diets resulted in significant elevation of plasma FGF23 vs rats fed NF diets: Experiment 1, 593 ± 126 vs 157 ± 28 pg/ ml (p < 0.01); Experiment 2, 538 ± 105 vs 250 ± 18 pg/ml (p < 0.05); Experiment 3, 971 ± 118 vs 534 ± 40 pg/ml (p < 0.01). Rats fed HF diets showed P retention and decreased renal klotho (ratio klotho/actin) vs rats fed NF diets: Experiment 1, 0.75 ± 0.06 vs 0.97 ± 0.02 (p < 0.01); Experiment 2, 0.69 ± 0.07 vs 1.12 ± 0.08 (p < 0.01); Experiment 3, 0.57 ± 0.19 vs 1.16 ± 0.15 (p < 0.05). Uremic rats fed HF diet showed more severe vascular calcification (VC) than rats fed NF diet (aortic Ca = 6.3 ± 1.4 vs 1.4 ± 0.1 mg/g tissue, p < 0.001). In conclusion, energy-rich diets increased plasma levels of FGF23, a known risk factor of cardiovascular morbidity and mortality. Even though FGF23 has major phosphaturic actions, feeding HF diets resulted in P retention, likely secondary to decreased renal klotho, and aggravated uremic V

In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/β-catenin activation

The present study investigates the differential effect of two vitamin D receptor agonists, calcitriol and paricalcitol, on human aortic smooth muscle cells calcification in vitro. Human vascular smooth muscle cells were incubated in a high phosphate (HP) medium alone or supplemented with either calcitriol 10−8M (HP + CTR) or paricalcitol 3·10−8 M (HP + PC). HP medium induced calcification, which was associated with the upregulation of mRNA expression of osteogenic factors such as bone morphogenetic protein 2 (BMP2), Runx2/Cbfa1, Msx2, and osteocalcin. In these cells, activation of Wnt/β-catenin signaling was evidenced by the translocation of β-catenin into the nucleus and the increase in the expression of direct target genes as cyclin D1, axin 2, and VCAN/versican. Addition of calcitriol to HP medium (HP + CTR) further increased calcification and also enhanced the expression of osteogenic factors together with a significant elevation of nuclear β-catenin levels and the expression of cyclin D1, axin 2, and VCAN. By contrast, the addition of paricalcitol (HP + PC) not only reduced calcification but also downregulated the expression of BMP2 and other osteoblastic phenotype markers as well as the levels of nuclear β-catenin and the expression of its target genes. The role of Wnt/β-catenin on phosphate- and calcitriol-induced calcification was further demonstrated by the inhibition of calcification after addition of Dickkopf-related protein 1 (DKK-1), a specific natural antagonist of the Wnt/β-catenin signaling pathway. In conclusion, the differential effect of calcitriol and paricalcitol on vascular calcification appears to be mediated by a distinct regulation of the BMP and Wnt/β-catenin signaling pathways

The Farallon-Aluk ridge collision with South America: Implications for the geochemical changes of slab window magmas from fore- to back-arc

The collision of a divergent ocean ridge may evolve into two end cases: in the continuity of ocean-floor subduction, or in the detachment of the subducted plate. The northern Patagonia active plate margin has the unique situation that in Cenozoic time it has been subjected to two divergent ridge collisions, each one representing one of the end members. The Neogene Antarctica-Nazca divergent ridge collision evolved as a continuous ocean-floor subduction system, promoting a magmatic hiatus at the arc axis, the obduction of part of the ridge ocean-floor in the fore-arc, and basaltic volcanism in the back-arc. In contrast, the Paleogene Farallon-Aluk divergent ridge collision evolved into a transform margin, with the detachment and sinking of the Aluk plate and the development of a large slab window. As in the previous case, this collision promoted a magmatic hiatus at the arc axis, but the tectono-magmatic scenario changed to postorogenic synextensional volcanism that spread to the former fore-arc (basalt, andesite, rhyolite) and former back-arc (bimodal ignimbrite flare-up, basalt). Geochemistry of this slab window synextensional volcanism shows more MORB-like basalts towards the former fore-arc, and MORB-OIB-like basalts towards the former back-arc. Instead, an isolated undeformable crustal block in the former back-arc, with an "epeirogenic" response to the slab window and extensional regime, was covered by OIB-type basalts after uplift. Major elements show that slab window basalts reach TiO2 values up to 3 wt%, as compared with the top value of 1.5 wt% of arc magmas. Besides, the MgO with respect to (FeOt + Al2O3) ratio helps to distinguish slab window magma changes from the former fore-arc to the former back-arc and also with respect to the "epeirogenic" block. Higher contents of HFS elements such as Nb and Ta also help to distinguish this slab window from arc magmas and also, to distinguish slab window magma changes from the former fore-arc to the former back-arc and "epeirogenic" block settings. The isotope compositions of slab window magmatism show a disparate coeval array from MORB to crustal sources, interpreted as a consequence of the lack of protracted storage and homogenization due to the extensional setting.Facultad de Ciencias Naturales y Muse

Magnesium Inhibits Wnt/β-Catenin Activity and Reverses the Osteogenic Transformation of Vascular Smooth Muscle Cells

Magnesium reduces vascular smooth muscle cell (VSMC) calcification in vitro but the mechanism has not been revealed so far. This work used only slightly increased magnesium levels and aimed at determining: a) whether inhibition of magnesium transport into the cell influences VSMC calcification, b) whether Wnt/β-catenin signaling, a key mediator of osteogenic differentiation, is modified by magnesium and c) whether magnesium can influence already established vascular calcification. Human VSMC incubated with high phosphate (3.3 mM) and moderately elevated magnesium (1.4 mM) significantly reduced VSMC calcification and expression of the osteogenic transcription factors Cbfa-1 and osterix, and up-regulated expression of the natural calcification inhibitors matrix Gla protein (MGP) and osteoprotegerin (OPG). The protective effects of magnesium on calcification and expression of osteogenic markers were no longer observed in VSMC cultured with an inhibitor of cellular magnesium transport (2-aminoethoxy-diphenylborate [2-APB]). High phosphate induced activation of Wnt/β-catenin pathway as demonstrated by the translocation of β-catenin into the nucleus, increased expression of the frizzled-3 gene, and downregulation of Dkk-1 gene, a specific antagonist of the Wnt/β-catenin signaling pathway. The addition of magnesium however inhibited phosphate-induced activation of Wnt/β-catenin signaling pathway. Furthermore, TRPM7 silencing using siRNA resulted in activation of Wnt/β-catenin signaling pathway. Additional experiments were performed to test the ability of magnesium to halt the progression of already established VSMC calcification in vitro. The delayed addition of magnesium decreased calcium content, down-regulated Cbfa-1 and osterix and up-regulated MGP and OPG, when compared with a control group. This effect was not observed when 2-APB was added. In conclusion, magnesium transport through the cell membrane is important to inhibit VSMC calcification in vitro. Inhibition of Wnt/β-catenin by magnesium is one potential intracellular mechanism by which this anti-calcifying effect is achieved

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution