R-RAS2 overexpression in tumors of the human central nervous system

Malignant tumors of the central nervous system (CNS) are the 10th most frequent cause of cancer mortality. Despite the strong malignancy of some such tumors, oncogenic mutations are rarely found in classic members of the RAS family of small GTPases. This raises the question as to whether other RAS family members may be affected in CNS tumors, excessively activating RAS pathways. The RAS-related subfamily of GTPases is that which is most closely related to classical Ras and it currently contains 3 members: RRAS, RRAS2 and RRAS3. While R-RAS and R-RAS2 are expressed ubiquitously, R-RAS3 expression is restricted to the CNS. Significantly, both wild type and mutated RRAS2 (also known as TC21) are overexpressed in human carcinomas of the oral cavity, esophagus, stomach, skin and breast, as well as in lymphomas. Hence, we analyzed the expression of R-RAS2 mRNA and protein in a wide variety of human CNS tumors and we found the R-RAS2 protein to be overexpressed in all of the 90 CNS cancer samples studied, including glioblastomas, astrocytomas and oligodendrogliomas. However, R-Ras2 was more strongly expressed in low grade (World Health Organization grades I-II) rather than high grade (grades III-IV) tumors, suggesting that R-RAS2 is overexpressed in the early stages of malignancy. Indeed, R-RAS2 overexpression was evident in pre-malignant hyperplasias, both at the mRNA and protein levels. Nevertheless, such dramatic changes in expression were not evident for the other two subfamily members, which implies that RRAS2 is the main factor triggering neural transformation.This work was supported by grants SAF2012-31279 from the ‘Comisión Interministerial de Ciencia y Tecnología’ and the ‘Ramón y Cajal’ program (RYC-2010-06251, to B.C.). We also thank the Fundación Ramón Areces for its institutional support of the ‘Centro de Biología Molecular Severo Ochoa’

Behavior of Phenols and Phenoxyacids on a Bisphenol-A Imprinted Polymer. Application for Selective Solid-Phase Extraction from Water and Urine Samples

A molecularly imprinted polymer (MIP), obtained by precipitation polymerisation with 4-vinylpyridine as the functional monomer, ethylene glycol dimethacrylate as cross-linker, and bisphenol-A (BPA) as template, was prepared. The binding site configuration of the BPA-MIP was examined using Scatchard analysis. Moreover, the behaviour of the BPA-MIP for the extraction of several phenolic compounds (bisphenol-A, bisphenol-F, 4-nitrophenol, 3-methyl-4-nitrophenol) and phenoxyacid herbicides such as 2,4-D, 2,4,5-T and 2,4,5-TP has been studied in organic and aqueous media in the presence of other pesticides in common use. It was possible to carry out the selective preconcentration of the target analytes from the organic medium with recoveries of higher than 70%. In an aqueous medium, hydrophobic interactions were found to exert a remarkably non-specific contribution to the overall binding process. Several parameters affecting the extraction efficiency of the BPA-MIP were evaluated to achieve the selective preconcentration of phenols and phenoxyacids from aqueous samples. The possibility of using the BPA-MIP as a selective sorbent to preconcentrate these compounds from other samples such as urine and river water was also explored

Exfoliation of Alpha-Germanium: A Covalent Diamond-Like Structure

2D materials have opened a new field in materials science with outstanding scientific and technological impact. A largely explored route for the preparation of 2D materials is the exfoliation of layered crystals with weak forces between their layers. However, its application to covalent crystals remains elusive. Herein, a further step is taken by introducing the exfoliation of germanium, a narrow-bandgap semiconductor presenting a 3D diamond-like structure with strong covalent bonds. Pure α-germanium is exfoliated following a simple one-step procedure assisted by wet ball-milling, allowing gram-scale fabrication of high-quality layers with large lateral dimensions and nanometer thicknesses. The generated flakes are thoroughly characterized by different techniques, giving evidence that the new 2D material exhibits bandgaps that depend on both the crystallographic direction and the number of layers. Besides potential technological applications, this work is also of interest for the search of 2D materials with new properties

Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns.This study was funded by Faes Farma, S.A. and Bruno Farmaceutici S.p.A. The authors wish to thank the study participants, research staff, the secondary investigators of the Osteoferol study group, the home nursing staff (Emibet), and Faes Farma clinical research team: Paula Arranz Gutiérrez, Lorena Elgezabal González, Mariana Frau Usoz, and Iñigo Saez Riesco. Medical writing support was provided by Francisco López de Saro (Trialance SCCL), funded by Faes Farma, S.A

Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D <20 ng/ml were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25,000 IU/month for 12 months. At month 4, 35.0% of postmenopausal women treated with calcifediol and 8.2% of those treated with cholecalciferol reached serum 25(OH)D levels above 30 ng/ml (p < 0.0001). The most remarkable difference between both drugs in terms of mean change in serum 25(OH)D levels was observed after the first month of treatment (mean ± standard deviation change = 9.7 ± 6.7 and 5.1 ± 3.5 ng/ml in patients treated with calcifediol and cholecalciferol, respectively). No relevant treatment-related safety issues were reported in any of the groups studied. These results thus confirm that calcifediol is effective, faster, and more potent than cholecalciferol in raising serum 25(OH)D levels and is a valuable option for the treatment of vitamin D deficiency

I.amAble: la ciencia (química) al alcance de toda la sociedad

En este proyecto de innovación, que nace con vocación de continuar en años sucesivos, se persigue mejorar la calidad de la formación de los estudiantes de la Facultad de Ciencias Químicas (F. CC.QQ.) en el ámbito de la docencia teórico-práctica y de la divulgación científica. El trabajo ha consistido en la preparación de unos experimentos prácticos para llevarlos a cabo en centros educativos no universitarios en los que se ha tenido en cuenta la participación conjunta de personas con y sin diversidad funcional, desde una perspectiva inclusiva colaborativa. Estas actividades las han realizado los estudiantes bajo la supervisión de profesores (PDI) y personal de administración y servicios (PAS). Los experimentos se han recogido en fichas didácticas para facilitar su desarrollo y aplicación por parte de otros usuarios. En estas fichas se explica detalladamente cómo realizar las experiencias en formato de taller. Las fichas de los talleres realizados están disponibles en una página web vinculada a la Universidad Complutense bajo el título I.amAble (iamable.ucm.es). Está página ha sido construida por un estudiante de la Facultad de Informática , bajo la supervisión de profesionales, tanto de esa facultad como del Instituto de Tecnología del Conocimiento, y está abierta a contribuciones similares de otras facultades y otras instituciones. La página web está diseñada de manera que resulte lo más intuitiva y accesible posible para todo tipo de público. Entre todos los experimentos se han elegido cuatro para llevarlos a la práctica en centros educativos como actividades inclusivas en las que han participado conjuntamente personas con y sin discapacidad. Con este proyecto se pretende mejorar la calidad docente al ofrecer a los estudiantes la posibilidad de aprender enseñando mediante una actividad semipresencial. El desarrollo por parte de los estudiantes de competencias transversales en educación y en divulgación de la ciencia facilitarán algunas salidas profesionales en el ámbito educativo formal (centros de enseñanza) o informal (museos, animación sociocultural). Otro aspecto importante a resaltar es la potenciación de la colaboración entre todos los miembros de la institución universitaria. Este proyecto pretende contribuir a la mejora de la cultura científica, así como al establecimiento de puentes entre la UCM y la sociedad a la que debe servir. Finalmente, es importante subrayar que incidirá en la inclusión de las personas con discapacidad como parte de la sociedad, a través del acercamiento compartido a la ciencia (Dimensiones de inclusión social y derechos de Schalock; NAVAS MACHO, P. y otros, 2012. Derechos de las personas con discapacidad intelectual: implicaciones de la Convención de Naciones Unidas. Siglo Cero. 43 (243): 7-28.)

Colecciones de referencia y oferta multimedia para la práctica arqueológica.

El Grado de Arqueología ha permitido introducir métodos pedagógicos de mayor calidad y herramientas multimedia. Este proyecto tiene por objetivo suministrar a los estudiantes del Grado de Arqueología las competencias básicas para entender y manejar los datos arqueológicos, a través de métodos de aprendizaje interactivos multimedia, reproducciones de artefactos antiguos y colecciones de referencia que integren la información usual de la investigación real en el campo arqueológic

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 +/- 20.6% vs 93.6 +/- 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 +/- 5.2 mm vs 19.9 +/- 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment