Melatonin enhancement of the radiosensitivity of human breast cancer cells is associated with the modulation of proteins involved in estrogen biosynthesis

Enhancing the radiosensitivity of cancer cells is one of the most important tasks in clinical radiobiology. Endocrine therapy and radiotherapy are two cancer treatmentmodalities which are often given together in patients with locally-advanced breast cancer and positive hormone-receptor status. Oncostatic actions of melatonin are relevant on estrogen-dependent mammary tumors. In the present study, we wanted to evaluate the effects of the combination of ionizing radiation and melatonin on proteins involved in estrogen biosynthesis in breast cancer cells.We demonstrated a role of melatonin in mediating the sensitization of human breast cancer cells to the ionizing radiation by decreasing around 50% the activity and expression of proteins involved in the synthesis of estrogens in these cells. Thus, melatonin pretreatment before radiation reduces the amount of active estrogens at cancer cell level. Melatonin 1 nM induced a 2-fold change in p53 expression as compared to radiation alone. The regulatory action of melatonin on p53 could be a link between melatonin and its modulatory action on the sensitivity of breast cancer cells to ionizing radiation. These findings may have implications for designing clinical trials using melatonin and radiotherapy

Electrochemical study of gold recovery from ammoniacal thiosulfate, simulating the PCBs leaching of mobile phones

[EN] The high volume of sales and the high degree of obsolescence of mobile phones, together with the reduction of the natural reserves of the metals used in the composition of their printed circuit boards (PCBs), makes the recycling of these devices economically and environmentally attractive. Moreover, the search for the reduction of toxicity levels inherent to the gold leaching processes with alternatives to cyanide, such as thiosulfate is a priority. Thus, it is necessary to search for efficient alternatives for the recovery of gold from solutions containing thiosulfate, in the presence of copper, used in the leaching of PCBs of mobile phones. One of these alternatives could be the electrochemical recovery of the metals present in solution. Thus, this study aimed to verify some variables involved in the process of recovery of gold and copper and to determine the electrochemical yield obtained for these solutions. Initially, cyclic scanning voltammetry with a rotating disk electrode (RDE) was performed to verify the electrochemical behavior of gold and copper in solution. Then, electrowinning tests were used to determine the recovery rates of these metals and to calculate the yield obtained in the process. The results showed that this electrochemical reaction is mass transport controlled, which allowed the calculation of the diffusion coefficients of the metal in solution. In real solutions, the gold fraction recovered reached a 94%, and the copper fraction recovered was 95%, applying electrode potential values of -500 mV(Ag/AgCl) and -700 mV(Ag/AgCl), respectively. The current efficiency for the gold electrowinning achieved in the experiments was lower than 3%. (c) 2017 Elsevier Ltd. All rights reserved.The authors would like to thank the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) from Brazil for financial support.Kasper, AC.; Veit, HM.; García Gabaldón, M.; Pérez-Herranz, V. (2018). Electrochemical study of gold recovery from ammoniacal thiosulfate, simulating the PCBs leaching of mobile phones. Electrochimica Acta. 259:500-509. https://doi.org/10.1016/j.electacta.2017.10.161S50050925

Accesibilidad en los espacios públicos urbanizados

El libro, coordinado por el Director de ACCEPLAN, Fernando Alonso López, viene a ser un reflejo de los avances entorno a la búsqueda de accessibilidad universal en los espacios públicos urbanizados. Para aproximarse a la realidad normativa y técnica de la Orden Ministerial el libro se estructura en artículos referentes al contexto normativo, a los contenidos de la Orden, y a reflexiones y criterios en torno a la accesibilidad en la ciudad. Del conjunto de artículos, por su variedad y por su carácter multidiciplinar, se extrae un libro de referencia que ofrece la variedad de enfoques del tema y que ayuda a interpretar mejor la Orden Ministerial, su contribución a los objetivos de la Ley 51/2003 de Igualdad de Oportunidades No Discriminación y Accesibilidad Universal, LIONDAU, y su utilidad en la comformación de unas ciudades cada vez más abiertas a la diversidad funcional y a la convivencia.El llibre, coordinat pel director de ACCEPLAN, Fernando Alonso López, ve a ser un reflex dels avenços entorn de la recerca d'accessibilitat universal en els espais públics urbanitzats. Per conèixer un realitat normativa i tècnica de l'Ordre Ministerial el llibre s'estructura en articles referents al context normatiu, als continguts de l'Ordre, ja reflexions i criteris al voltant de l'accessibilitat a la ciutat. Del conjunt d'articles, per la seva varietat i pel seu caràcter multidiciplinar, s'extreu un llibre de referència que ofereix la varietat d'enfocaments del tema i que ajuda a interpretar millor l'Ordre Ministerial, la seva contribució als objectius de la Llei 51/2003 de Igualtat d'Oportunitats No Discriminació i Accessibilitat Universal, LIONDAU, i la seva utilitat en la comformación d'unes ciutats cada vegada més obertes a la diversitat funcional ia la convivència

Factors associated with the clinical outcome of patients with relapsed/refractory CD19+acute lymphoblastic leukemia treated with ARI-0001 CART19-cell therapy

The prognosis of patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains poor, particularly for those relapsing after allogeneic hema-topoietic cell transplantation (alloHCT). Novel agents such as inotuzumab ozogamicin or blinatumomab achieve increased response rates, but these are generally transient unless followed by alloHCT. Chimeric antigen receptors (CAR) targeting CD19 have shown promising results in R/R ALL, and one of these products (tisagenlecleucel) has been approved for the treatment of patients with R/R ALL up to 25 years of age

Magnetic properties of early Pliocene sediments from IODP Site U1467 (Maldives platform) reveal changes in the monsoon system

We report a study of the magnetic stratigraphy and the anisotropy of isothermal remanent magnetization of Pliocene sediments from International Ocean Discovery Program (IODP) Site U1467 drilled in the Maldives platform (Indian Ocean) during Exp. 359. Magnetic stratigraphy gives a precise record of geomagnetic reversals of the early Pliocene from approximately 5.3 Ma to 3.1 Ma providing a detailed age model in an interval where the biostratigraphic record is scarce. We use the anisotropy of isothermal remanent magnetization (AIRM) to investigate the statistical orientation of fine magnetic particles and provide data on the strength and direction of bottom currents during the early Pliocene. The strength of bottom currents recorded by the AIRM, shows a prominent increase at the top of Chron C3n.1n (about 4.2 Ma), and the current direction (NE - SW) is consistent with that of modern instrumental measurements. Since bottom currents in the Maldives are driven by the monsoon, we speculate that the 4.2 Ma increase of bottom currents could mark the onset of the present-day setting, probably related to the coeval uplift phase of the Himalayan plateau

Carbonate delta drift: a new sediment drift type

Based on high-resolution reflection seismic and core data from IODP Expedition 359 we present a new channel-related drift type attached to a carbonate platform slope, which we termed delta drift. Like a river delta, it is comprised of several stacked lobes and connected to a point source. The delta drifts were deposited at the exit of two gateways that connect the Inner Sea of the Maldives carbonate platform with the open ocean. The channels served as conduits focusing and accelerating the water flow; Entrained material was deposited at their mouth where the flows relaxed. The lobe-shaped calcareous sediment drifts must have formed under persistent water through flow. Sediment supply was relatively high and continuous, resulting in an average sedimentation rate of 17 cm ka−1. The two delta drifts occupy 342 and 384 km2, respectively; with a depositional relief of approximately 500 m. They have a sigmoidal clinoform reflection pattern with a particular convex upward bending of the foresets. In the Maldives the drift onset marks the transition from a sea-level controlled to a progressively current dominated depositional regime. This major event occurred in the Serravallian about 13 Ma ago, leading to the partial drowning of the carbonate platform and the creation of shallow seaways. The initial bank-enclosed topography resembles an “empty bucket” geometry which is rapidly filled by the drift sediments that aggrade and prograde into the basin. Thereby the depositional environment of the delta drifts changes from deep water (>500) to shallow-water conditions at their topsets, indicated by the overall coarsening upward trend in grain size and the presence of shallow water large benthic foraminifers at their top

Cyclic anoxia and organic rich carbonate sediments within a drowned carbonate platform linked to Antarctic ice volume changes: Late Oligocene-early Miocene Maldives

This paper reports on the newly discovered occurrence of thick sequences (∼100 m) of Late Oligocene and Early Miocene (∼24.9 to ∼20 Ma) interbedded organic-rich sediments (sapropels) and pelagic (organic poor) carbonates at Sites U1466 and U1468 drilled in the Maldives archipelago during the International Ocean Discovery Program (IODP) Expedition 359. This occurrence is unusual in that this sequence is located > 1000 m above the surrounding ocean floor within an inter-atoll basin and not linked to any known global oceanic events. Total organic content reaches as high as 35% in the darker layers, while the interbedded carbonates have concentrations of less than 0.1%. Trace elements characteristic of anoxic waters, such as Mo, V, Cr, U, and Pb, correlate positively with concentrations of organic carbon. Nitrogen isotopic data show no evidence that the intervals of high total organic carbon are related to enhanced productivity driven by upwelling. Instead, high organic carbon is associated with intervals of anoxia. We propose that sea-level fluctuations linked to changes in Antarctic ice volume restricted exchange with the open ocean causing bottom waters of the inter-atoll basin to become anoxic periodically. The architecture of the platform at the end of the Oligocene, combined with the global sea-level highstand, set the stage for orbitally-driven sea-level changes producing cyclic deposition of sapropels. The proposed mechanism may serve as an analogue for other occurrences of organic carbon-rich sediments within carbonate platform settings.</p

Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. clinicaltrials.gov identifier:02869074

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio