The Open Cluster Chemical Abundances from Spanish Observatories survey (OCCASO)

We present the motivation, design and current status of the Open Cluster Chemical Abundances from Spanish Observatories survey (OCCASO). Using the high resolution spectroscopic facilities available at Spanish observatories, OCCASO will derive chemical abundances in a sample of 20 to 25 open clusters older than 0.5 Gyr. This sample will be used to study in detail the formation and evolution of the Galactic disc using open clusters as tracers.Comment: 6 pages, 1 figure, Highlights of Spanish Astrophysics VIII, Proceedings of the XI Scientific Meeting of the Spanish Astronomical Society held on September 8 - 12, 2014, in Teruel, Spain. A. J. Cenarro, F. Figueras, C. Hern\'andez-Monteagudo, J. Trujillo, and L. Valdivielso (eds.

A novel phosphatidylinositol 3-kinase (PI3K) inhibitor directs a potent FOXO-dependent, p53-independent cell cycle arrest phenotype characterized by the differential induction of a subset of FOXO-regulated genes.

INTRODUCTION: The activation of the phosphoinositide 3-kinase (PI3K)/AKT signalling pathway is one the most frequent genetic events in breast cancer, consequently the development of PI3K inhibitors has attracted much attention. Here we evaluate the effect of PI3K inhibition on global gene expression in breast cancer cells. METHODS: We used a range of methodologies that include in silico compound analysis, in vitro kinase assays, cell invasion assays, proliferation assays, genome-wide transcription studies (Agilent Technologies full genome arrays), gene set enrichment analysis, quantitative real-time PCR, immunoblotting in addition to chromatin immunoprecipitation. RESULTS: We defined the physico-chemical and the biological properties of ETP-45658, a novel potent PI3K inhibitor. We demonstrated that ETP-45658 potently inhibited cell proliferation within a broad range of human cancer cells, most potently suppressing the growth of breast cancer cells via inhibiting cell cycle. We show that this response is Forkhead box O (FOXO) protein dependent and p53 independent. Our genome-wide microarray analysis revealed that the cell cycle was the most affected biological process after exposure to ETP-45658 (or our control PI3K inhibitor PI-103), that despite the multiple transcription factors that are regulated by the PI3K/AKT signalling cascade, only the binding sites for FOXO transcription factors were significantly enriched and only a subset of all FOXO-dependent genes were induced. This disparity in gene transcription was not due to differential FOXO promoter recruitment. CONCLUSIONS: The constitutive activation of PI3Ks and thus the exclusion of FOXO transcription factors from the nucleus is a key feature of breast cancer. Our results presented here highlight that PI3K inhibition activates specific FOXO-dependent genes that mediate cell cycle arrest in breast cancer cells

Co-Targeting PIM Kinase and PI3K/mTOR in NSCLC

PIM kinases are constitutively active proto-oncogenic serine/threonine kinases that play a role in cell cycle progression, metabolism, inflammation and drug resistance. PIM kinases interact with and stabilize p53, c-Myc and parallel signaling pathway PI3K/Akt. This study evaluated PIM kinase expression in NSCLC and in response to PI3K/mTOR inhibition. It investigated a novel preclinical PI3K/mTOR/PIM inhibitor (IBL-301) in vitro and in patient-derived NSCLC tumor tissues. Western blot analysis confirmed PIM1, PIM2 and PIM3 are expressed in NSCLC cell lines and PIM1 is a marker of poor prognosis in patients with NSCLC. IBL-301 decreased PIM1, c-Myc, pBAD and p4EBP1 (Thr37/46) and peIF4B (S406) protein levels in-vitro and MAP kinase, PI3K-Akt and JAK/STAT pathways in tumor tissue explants. IBL-301 significantly decreased secreted pro-inflammatory cytokine MCP-1. Altered mRNA expression, including activated PIM kinase and c-Myc, was identified in Apitolisib resistant cells (H1975GR) by an IL-6/STAT3 pathway array and validated by Western blot. H1975GR cells were more sensitive to IBL-301 than parent cells. A miRNA array identified a dysregulated miRNA signature of PI3K/mTOR drug resistance consisting of regulators of PIM kinase and c-Myc (miR17-5p, miR19b-3p, miR20a-5p, miR15b-5p, miR203a, miR-206). Our data provides a rationale for co-targeting PIM kinase and PI3K-mTOR to improve therapeutic response in NSCLC

Biometrical analysis reveals major differences between the two subspecies of the European rabbit

The climatic oscillations that have occurred in the last few million years have strongly affected species distribution ranges. Highly divergent genetic lineages arose, some of which correspond to recognized subspecies that currently occupy small geographical areas. Understanding the implications of the genetic differences between these subspecies is crucial for proper conservation of Evolutionarily Significant Units. We use the two European rabbit subspecies, Oryctolagus cuniculus cuniculus and O. c. algirus, in the Iberian Peninsula as a model to investigate the repercussions at the biometric level of their largely recognized genetic differentiation. To accomplish this we analysed the ear and hind foot length, and the body mass of 999 adult rabbits from 27 locations across the distribution range of both subspecies in their native range, the Iberian Peninsula. Our results show biometric differences between the two subspecies, also explained by geographical location and sex, O. c. algirus being lighter and having shorter ear and hind foot lengths. We examine these findings under an evolutionary framework, and discuss their implications for current conservation efforts. Future research should focus on the ecological implications of these biometric differences, namely potential different habitat use and anti-predatory strategies in the species' native range.This study was partially funded by Projects PAI06-170, VP-0119-07,POII09-0099-2557, CGL2009-11665, 2012-30E060, CGL2013-43197, CGL2013-43197-R, FCT research project (PTDC/BIA-EVF/111368/2009), and ‘Genomics Applied to Genetic Resources’ co-funded by North Portugal Regional Operational Programme 2007/2013 (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF). C.F. was supported by a PhD grant (Ref. SFRH/BD/22084/2005) and a postdoctoral grant (Ref. SFRH/BPD/88643/2012), and J.B.-A. by a postdoctoral grant (Ref. SFRH/BPD/65464/2009) all from the Fundaçao para a Ciência e Tecnologia of the Ministêrio da Ciência, Tecnologia e Ensino Superior, Portuguese government. C.F. is currently supported by a Marie Curie Out going International Fellowship for Career Development (PIOF-GA-2013-621571) within the 7th Framework Programme of the European Union. M.D.-M. is currently funded by Consejería de Economía, Innovación, Ciencia y Empleo of Junta de Andalucía, and the European Union’s SeventhFramework Programme for research, technological development and demonstration under grant agreement 267226. C.A.R.-S. was supported by a doctoral grant from the National Council of Science and Technology of Mexico (CONACyT). P.C.A. was supportedby an FCT sabbatical grant (SFRH/BSAB/1278/2012) and by FLAD (Luso-American Foundation).Peer Reviewe

mTORC2 Is the major second layer kinase negatively regulating FOXO3 activity

Forkhead box O (FOXO) proteins are transcription factors involved in cancer and aging and their pharmacological manipulation could be beneficial for the treatment of cancer and healthy aging. FOXO proteins are mainly regulated by post-translational modifications including phosphorylation, acetylation and ubiquitination. As these modifications are reversible, activation and inactivation of FOXO factors is attainable through pharmacological treatment. One major regulatory input of FOXO signaling is mediated by protein kinases. Here, we use specific inhibitors against different kinases including PI3K, mTOR, MEK and ALK, and other receptor tyrosine kinases (RTKs) to determine their effect on FOXO3 activity. While we show that inhibition of PI3K efficiently drives FOXO3 into the cell nucleus, the dual PI3K/mTOR inhibitors dactolisib and PI-103 induce nuclear FOXO translocation more potently than the PI3Kδ inhibitor idelalisib. Furthermore, specific inhibition of mTOR kinase activity affecting both mTORC1 and mTORC2 potently induced nuclear translocation of FOXO3, while rapamycin, which specifically inhibits the mTORC1, failed to affect FOXO3. Interestingly, inhibition of the MAPK pathway had no effect on the localization of FOXO3 and upstream RTK inhibition only weakly induced nuclear FOXO3. We also measured the effect of the test compounds on the phosphorylation status of AKT, FOXO3 and ERK, on FOXO-dependent transcriptional activity and on the subcellular localization of other FOXO isoforms. We conclude that mTORC2 is the most important second layer kinase negatively regulating FOXO activity.info:eu-repo/semantics/publishedVersio

Assessment of oceanographic services for the monitoring of highly anthropised coastal lagoons: The Mar Menor case study

Ocean monitoring systems are designed for continuous monitoring to track their evolution and anticipate environmental issues. However, they are often based on IoT systems that offer little spatial coverage and are hard to maintain. Satellite remote sensing offers good geographical coverage but they also face several challenges to become a monitoring system. This paper introduces an easy-to-use software tool to crawl water-quality data from up to 6 satellite instruments from the ESA and NASA. Particularly, Chl-a data is deeply analyzed in terms of reliability and data coverage for a highly anthropised coastal lagoon (Mar Menor, Spain), where serious socio-environmental issues are happening. Our results show a good linear correlation between in situ data and SRS data, reaching values close to 0.9, and stating the relevance of organic matter inputs from ephemeral streams in Chl-a concentrations. Moreover, temporal granularity is increased from 5 to 1.5 days by combining SRS sources.Preprin

The OCCASO survey: presentation and radial velocities of 12 Milky Way open clusters

Open clusters (OCs) are crucial for studying the formation and evolution of the Galactic disc. However, the lack of a large number of OCs analysed homogeneously hampers the investigations about chemical patterns and the existence of Galactocentric radial and vertical gradients, or an age-metallicity relation. To overcome this, we have designed the Open Cluster Chemical Abundances from Spanish Observatories (OCCASO) survey. We aim to provide homogeneous radial velocities, physical parameters and individual chemical abundances of six or more red clump stars for a sample of 25 old and intermediate-age OCs visible from the Northern hemisphere. To do so, we use high-resolution spectroscopic facilities (R >= 62 000) available at Spanish observatories. We present the motivation, design and current status of the survey, together with the first data release of radial velocities for 77 stars in 12 OCs, which represents about 50 per cent of the survey. We include clusters never studied with high-resolution spectroscopy before (NGC 1907, NGC 6991, NGC 7762), and clusters in common with other large spectroscopic surveys like the Gaia-ESO Survey (NGC 6705) and Apache Point Observatory Galactic Evolution Experiment (NGC 2682 and NGC 6819). We perform internal comparisons between instruments to evaluate and correct internal systematics of the results, and compare our radial velocities with previous determinations in the literature, when available. Finally, radial velocities for each cluster are used to perform a preliminary kinematic study in relation with the Galactic disc

Vertical distribution of Atlantic bluefin tuna Thunnus thynnus and bonito Sarda sarda larvae is related to temperature preference

As part of the endeavor aiming at the domestication of Atlantic bluefin tuna (BFT; Thunnus thynnus), first sexual maturity in captivity was studied by documenting its occurrence and by characterizing the key hormones of the reproductive axis: follicle stimulating hormone (FSH) and luteinizing hormone (LH). The full length sequence encoding for the related hormone b-subunits, bftFSHb and bftLHb, were determined, revealing two bftFSHb mRNA variants, differing in their 50 untranslated region. A quantitative immuno-dot-blot assay to measure pituitary FSH content in BFT was developed and validated enabling, for the first time in this species, data sets for both LH and FSH to be compared. The expression and accumulation patterns of LH in the pituitary showed a steady increase of this hormone, concomitant with fish age, reaching higher levels in adult females compared to males of the same age class. Conversely, the pituitary FSH levels were elevated only in 2Y and adult fish. The pituitary FSH to LH ratio was consistently higher (>1) in immature than in maturing or pubertal fish, resembling the situation in mammals. Nevertheless, the results suggest that a rise in the LH storage level above a minimum threshold may be an indicator of the onset of puberty in BFT females. The higher pituitary LH levels in adult females over males may further support this notion. In contrast three year-old (3Y) males were pubertal while cognate females were still immature. However, it is not yet clear whether the advanced puberty in the 3Y males was a general feature typifying wild BFT populations or was induced by the culture conditions. Future studies testing the effects of captivity and hormonal treatments on precocious maturity may allow for improved handling of this species in a controlled environment which would lead to more cost-efficient farmingVersión del edito

The Open Cluster Chemical Abundances from Spanish Observatories survey (OCCASO)

We present the motivation, design and current status of the Open Cluster Chemical Abundances from Spanish Observatories survey (OCCASO). Using the high resolution spectroscopic facilities available at Spanish observatories, OCCASO will derive chemical abundances in a sample of 20 to 25 OCs older than 0.5 Gyr. This sample will be used to study in detail de formation and evolution of the Galactic disc using OCs as tracers. <P /