Genetic variants related to nicotine dependence

Large-scale population studies have proved that genetic factors contribute to individual differences in smoking behavior. Genes responsible for nicotine's pharmacokinetics and pharmacodynamics seem mainly involved, although a significant fraction of variance remains unexplained. In this study we examined 10 SNPs from 8 candidate genes with positive previous reports of association with smoking. A total of 454 Italian unrelated subjects were genotyped by a multiplex minisequencing assay through the SNaPShot kit. Cases were chosen as current and former nicotine dependent (FTND. >. 4 and SQ. >. 15), while controls were smoking-exposed but non-dependent and never smoker individuals (FTND = 0 and SQ < 10 and FTND = 0 and SQ = 0, respectively). Preliminary results shows that the SNPs CHRNA5-rs16969968 and CHRNA3-rs1051730 could be associated with risk of developing nicotine dependence. Factors as age, sex, and exposition to smoke were also found as possible factors of risk of nicotine addiction. The identification of susceptibility loci for individual response to substance abuse is particularly motivating for medicine for the global epidemic dimension of addictions and the urgent need of effective preventive and therapeutic strategies. 2011 Elsevier Ireland Ltd

The transitional gap transient AT 2018hso: new insights into the luminous red nova phenomenon

Context. The absolute magnitudes of luminous red novae (LRNe) are intermediate between those of novae and supernovae (SNe), and show a relatively homogeneous spectro-photometric evolution. Although they were thought to derive from core instabilities in single stars, there is growing support for the idea that they are triggered by binary interaction that possibly ends with the merging of the two stars. Aims. AT 2018hso is a new transient showing transitional properties between those of LRNe and the class of intermediate-luminosity red transients (ILRTs) similar to SN 2008S. Through the detailed analysis of the observed parameters, our study supports that it actually belongs to the LRN class and was likely produced by the coalescence of two massive stars. Methods. We obtained ten months of optical and near-infrared photometric monitoring, and 11 epochs of low-resolution optical spectroscopy of AT 2018hso. We compared its observed properties with those of other ILRTs and LRNe. We also inspected the archival Hubble Space Telescope (HST) images obtained about 15 years ago to constrain the progenitor properties. Results. The light curves of AT 2018hso show a first sharp peak (reddening-corrected M-r = -13.93 mag), followed by a broader and shallower second peak that resembles a plateau in the optical bands. The spectra dramatically change with time. Early-time spectra show prominent Balmer emission lines and a weak [Ca II] doublet, which is usually observed in ILRTs. However, the strong decrease in the continuum temperature, the appearance of narrow metal absorption lines, the great change in the H alpha strength and profile, and the emergence of molecular bands support an LRN classification. The possible detection of a M-I similar to -8 mag source at the position of AT 2018hso in HST archive images is consistent with expectations for a pre-merger massive binary, similar to the precursor of the 2015 LRN in M101. Conclusions. We provide reasonable arguments to support an LRN classification for AT 2018hso. This study reveals growing heterogeneity in the observables of LRNe than has been thought previously, which is a challenge for distinguishing between LRNe and ILRTs. This suggests that the entire evolution of gap transients needs to be monitored to avoid misclassifications

A comparison of Thellier-type and multispecimen paleointensity determinations on Pleistocene and historical lava flows from Lanzarote (Canary Islands, Spain)

Sixteen Miocene, Pleistocene, and historic lava flows have been sampled in Lanzarote (Canary Islands) for paleointensity analysis with both the Coe and multispecimen methods. Besides obtaining new data, the main goal of the study was the comparison of paleointensity results determined with two different techniques. Characteristic Remanent Magnetization (ChRM) directions were obtained in 15 flows, and 12 were chosen for paleointensity determination. In Thellier-type experiments, a selection of reliable paleointensity determinations (43 of 78 studied samples) was performed using sets of criteria of different stringency, trying to relate the quality of results to the strictness of the chosen criteria. Uncorrected and fraction and domain-state corrected multispecimen paleointensity results were obtained in all flows. Results with the Coe method on historical flows either agree with the expected values or show moderately lower ones, but multispecimen determinations display a large deviation from the expected result in one case. No relation can be detected between correct or anomalous results and paleointensity determination quality or rock-magnetic properties. However, results on historical flows suggest that agreement between both methods could be a good indicator of correct determinations. Comparison of results obtained with both methods on seven Pleistocene flows yields an excellent agreement in four and disagreements in three cases. Pleistocene determinations were only accepted if either results from both methods agreed or a result was based on a sufficiently large number (n>4) of individual Thellier-type determinations. In most Pleistocene flows, a VADM around 5 31022 Am2 was observed, although two flows displayed higher values around 931022 Am2.project CGL2012-32149 (Ministerio de Econom ıa y Competitividad, Spain), project 320/2011 (Ministerio de Medio Ambiente y Medio Rural y Marino, Spain) and the European Regional Development Fund (ERDF)

The helicase HAGE prevents interferon-a-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1

The tumour suppressor PML (promyelocytic leukaemia protein) regulates several cellular pathways involving cell growth, apoptosis, differentiation and senescence. PML also has an important role in the regulation of stem cell proliferation and differentiation. Here, we show the involvement of the helicase HAGE in the transcriptional repression of PML expression in ABCB5 + malignant melanoma-initiating cells (ABCB5 + MMICs), a population of cancer stem cells which are responsible for melanoma growth, progression and resistance to drug-based therapy. HAGE prevents PML gene expression by inhibiting the activation of the JAK-STAT (janus kinase-signal transducers and activators of transcription) pathway in a mechanism which implicates the suppressor of cytokine signalling 1 (SOCS1). Knockdown of HAGE led to a significant decrease in SOCS1 protein expression, activation of the JAK-STAT signalling cascade and a consequent increase of PML expression. To confirm that the reduction in SOCS1 expression was dependent on the HAGE helicase activity, we showed that SOCS1, effectively silenced by small interfering RNA, could be rescued by re-introduction of HAGE into cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes SOCS1 mRNA unwinding and protein expression in vitro

The long-lived Type IIn SN 2015da: Infrared echoes and strong interaction within an extended massive shell star star star

In this paper we report the results of the first similar to four years of spectroscopic and photometric monitoring of the Type IIn supernova SN 2015da (also known as PSN J13522411+3941286, or iPTF16tu). The supernova exploded in the nearby spiral galaxy NGC 5337 in a relatively highly extinguished environment. The transient showed prominent narrow Balmer lines in emission at all times and a slow rise to maximum in all bands. In addition, early observations performed by amateur astronomers give a very well-constrained explosion epoch. The observables are consistent with continuous interaction between the supernova ejecta and a dense and extended H-rich circumstellar medium. The presence of such an extended and dense medium is difficult to reconcile with standard stellar evolution models, since the metallicity at the position of SN 2015da seems to be slightly subsolar. Interaction is likely the mechanism powering the light curve, as confirmed by the analysis of the pseudo bolometric light curve, which gives a total radiated energy greater than or similar to 10(51) erg. Modeling the light curve in the context of a supernova shock breakout through a dense circumstellar medium allowed us to infer the mass of the prexisting gas to be similar or equal to 8 M-circle dot, with an extreme mass-loss rate for the progenitor star similar or equal to 0.6 M-circle dot yr(-1), suggesting that most of the circumstellar gas was produced during multiple eruptive events. Near- and mid-infrared observations reveal a fluxexcess in these domains, similar to those observed in SN 2010jl and other interacting transients, likely due to preexisting radiatively heated dust surrounding the supernova. By modeling the infrared excess, we infer a mass greater than or similar to 0.4 x 10(-3) M-circle dot for the dustSpanish MICINN gran

Microvesicles: ROS scavengers and ROS producers

This review analyzes the relationship between microvesicles and reactive oxygen species (ROS). This relationship is bidirectional; on the one hand, the number and content of microvesicles produced by the cells are affected by oxidative stress conditions; on the other hand, microvesicles can directly and/or indirectly modify the ROS content in the extra- as well as the intracellular compartments. In this regard, microvesicles contain a pro-oxidant or antioxidant machinery that may produce or scavenge ROS: direct effect. This mechanism is especially suitable for eliminating ROS in the extracellular compartment. Endothelial microvesicles, in particular, contain a specific and well-developed antioxidant machinery. On the other hand, the molecules included in microvesicles can modify (activate or inhibit) ROS metabolism in their target cells: indirect effect. This can be achieved by the incorporation into the cells of ROS metabolic enzymes included in the microvesicles, or by the regulation of signaling pathways involved in ROS metabolism. Proteins, as well as miRNAs, are involved in this last effect

La gran erupción de hace 4.2 ka cal en Cerro Blanco, Zona Volcánica Central, Andes: nuevos datos sobre los depósitos eruptivos holocenos en la Puna sur y regiones adyacentes

The eruption of the Cerro Blanco Volcanic Complex, in the southern Puna, NW Argentina dated at 4410–4150 a cal BP, was investigated to produce new information on stratigraphy, geomorphology, physical volcanology, radiocarbon dating, petrography, and geochemistry. Identification of pre–, syn–, and post–caldera products allowed us to estimate the distribution of the Plinian fallout during the paroxysmal syn–caldera phase of the eruption. The new results provide evidence for a major rhyolitic explosive eruption that spread volcanic deposits over an area of ~500,000 km2, accumulating > 100 km3 of tephra (bulk volume). This last value exceeds the lower threshold of Volcanic Explosive Index (VEI) of 7. Ash-fall deposits mantled the region at distances > 400 km from source and thick pyroclastic-flow deposits filled neighbouring valleys up to 35 km away. This eruption is the largest documented during the past five millennia in the Central Volcanic Zone of the Andes, and is probably one of the largest Holocene explosive eruptions in the world. We have also identified two additional rhyolitic eruptions in the region from two other eruptive sources: one during the Early–Holocene and another in the Late–Holocene. The identification and characterisation of these significant volcanic events provide new constraints into regional Holocene geological and archaeological records, and offer extensive regional chronostratigraphic markers over a wide geographical area of South America.La erupción del Complejo Volcánico Cerro Blanco en el sur de la Puna, noroeste de Argentina (4410–4150 a BP) se investigó para obtener nueva información sobre estratigrafía, geomorfología, volcanología física, dataciones por radiocarbono, petrografía y geoquímica. La caracterización de los productos en relación a la evolución de la caldera de Cerro Blanco permitió estimar la distribución de los depósitos de ceniza de la fase paroxísmica Plineana de la erupción. Estos novedosos resultados evidencian una gran erupción explosiva riolítica que generó depósitos cineríticos en un área de aproximadamente 500.000 km2, acumulando > 100 km3 de tefra (volumen total). Este último valor supera el umbral inferior del Índice de Explosividad Volcánica (IEV) de 7. Los depósitos de caída de ceniza cubrieron la región, llegando a más de 400 km desde el Complejo Volcánico de Cerro Blanco, y los potentes depósitos de flujos piroclásticos rellenaron los valles vecinos alcanzando una distancia de 35 km. Esta erupción es la más grande documentada durante los últimos cinco milenios en la Zona Volcánica Central de los Andes y es probablemente una de las mayores erupciones explosivas holocenas del mundo. Además, se han identificado otras dos erupciones riolíticas en la región procedentes de otros dos centros eruptivos: una durante el Holoceno temprano y otra en el Holoceno tardío. La identificación y caracterización de estos grandes eventos volcánicos proporcionan nuevas guías para los registros geológicos y arqueológicos regionales del Holoceno, siendo marcadores cronostratigráficos de aplicación a una extensa área geográfica de América del Sur

Tools for Embedding and Assessing Sustainable Development Goals in Engineering Education

This paper presents three tools developed within the framework of the project EDINSOST2-SDG, aimed at embedding and assessing the Education for Sustainable Development (ESD) in Engineering curricula. ESD is promoted through the introduction into engineering curricula of learning outcomes related to sustainability and, specifically, to the Sustainable Development Goals (SDG). The first tool, the ‘Engineering Sustainability Map’, contains ESD-related learning outcomes that any engineering student should have acquired upon completion of their studies. These learning outcomes are described according to four sustainability competencies: (1) Critical contextualization of knowledge, (2) Sustainable use of resources, (3) Participation in community processes, and (4) Application of ethical principles. The second tool, the ‘Sustainability Presence Map’ of a degree, shows the percentage of the presence in the curriculum of each sustainability competency. The calculation of the presence of each competency is based upon the effective integration of the related learning outcomes in a specific curriculum. Respective data are provided by teachers responsible for the coordination of the different subjects of the degree, collected through a questionnaire. The third tool presented is a questionnaire aimed at measuring the level of ESD that students perceive they have acquired through each competency. The comparison of data resulting from the Sustainability Presence Map with the data from the student questionnaire allows to determine the effectiveness of embedding ESD in a degree. The three tools presented in this work have undergone a validation process and are currently being used in a set of engineering degrees related to the EDINSOST2-SDG project. The results of the application of these tools is part of the future research work of the authors

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer

Background Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. Methods A panel of ER+ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1wt or ESR1Y537S, modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Results Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001. Conclusions Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER