Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - http://www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.

Finding revelation in anthropology: Alexander Winchell, William Robertson Smith and the heretical imperative

Anthropological inquiry has often been considered an agent of intellectual secularization. Not least is this so in the sphere of religion, where anthropological accounts have often been taken to represent the triumph of naturalism. This metanarrative however fails to recognise that naturalistic explanations could sometimes be espoused for religious purposes and in defence of confessional creeds. This essay examines two late nineteenth-century figures – Alexander Winchell in the United States, and William Robertson Smith in Britain – who found in anthropological analysis resources to bolster rather than undermine faith. In both cases these individuals found themselves on the receiving end of ecclesiastical censure and were dismissed from their positions at church-governed institutions. But their motivation was to vindicate divine revelation, in Winchell’s case from the physical anthropology of human origins and in Smith’s from the cultural anthropology of Semitic ritual.

Research in Progress: Medical Research Council United Kingdom Refractory Asthma Stratification Programme (RASP-UK)

The UK Refractory Asthma Stratification Programme(RASP-UK) will explore novel biomarker stratificationstrategies in severe asthma to improve clinicalmanagement and accelerate development of newtherapies. Prior asthma mechanistic studies have notstratified on inflammatory phenotype and theunderstanding of pathophysiological mechanisms inasthma without Type 2 cytokine inflammation is limited.RASP-UK will objectively assess adherence tocorticosteroids (CS) and examine a novel compositebiomarker strategy to optimise CS dose; this will alsoaddress what proportion of patients with severe asthmahave persistent symptoms without eosinophilic airwaysinflammation after progressive CS withdrawal. There will be interactive partnership with the pharmaceutical industry to facilitate access to stratified populations for novel therapeutic studies.

Early-type stars observed in the ESO UVES Paranal Observatory Project - V. Time-variable interstellar absorption

The structure and properties of the diffuse interstellar medium (ISM) on small scales, sub-au to 1 pc, are poorly understood. We compare interstellar absorption-lines, observed towards a selection of O- and B-type stars at two or more epochs, to search for variations over time caused by the transverse motion of each star combined with changes in the structure in the foreground ISM. Two sets of data were used: 83 VLT- UVES spectra with approximately 6 yr between epochs and 21 McDonald observatory 2.7m telescope echelle spectra with 6 - 20 yr between epochs, over a range of scales from 0 - 360 au. The interstellar absorption-lines observed at the two epochs were subtracted and searched for any residuals due to changes in the foreground ISM. Of the 104 sightlines investigated with typically five or more components in Na I D, possible temporal variation was identified in five UVES spectra (six components), in Ca II, Ca I and/or Na I absorption-lines. The variations detected range from 7\% to a factor of 3.6 in column density. No variation was found in any other interstellar species. Most sightlines show no variation, with 3{\sigma} upper limits to changes of the order 0.1 - 0.3 dex in Ca II and Na I. These variations observed imply that fine-scale structure is present in the ISM, but at the resolution available in this study, is not very common at visible wavelengths. A determination of the electron densities and lower limits to the total number density of a sample of the sightlines implies that there is no striking difference between these parameters in sightlines with, and sightlines without, varying components.

PESSTO: Survey description and products from the first data release by the Public ESO Spectroscopic Survey of Transient Objects

Context. The Public European Southern Observatory Spectroscopic Survey of Transient Objects (PESSTO) began as a public spectroscopic survey in April 2012. PESSTO classifies transients from publicly available sources and wide-field surveys, and selects science targets for detailed spectroscopic and photometric follow-up. PESSTO runs for nine months of the year, January - April and August - December inclusive, and typically has allocations of 10 nights per month. 

Aims. We describe the data reduction strategy and data products that are publicly available through the ESO archive as the Spectroscopic Survey data release 1 (SSDR1). 

Methods. PESSTO uses the New Technology Telescope with the instruments EFOSC2 and SOFI to provide optical and NIR spectroscopy and imaging. We target supernovae and optical transients brighter than 20.5^m for classification. Science targets are selected for follow-up based on the PESSTO science goal of extending knowledge of the extremes of the supernova population. We use standard EFOSC2 set-ups providing spectra with resolutions of 13-18 Å between 3345-9995 Å. A subset of the brighter science targets are selected for SOFI spectroscopy with the blue and red grisms (0.935-2.53 μm and resolutions 23-33 Å) and imaging with broadband JHK<inf>s</inf> filters. 

Results. This first data release (SSDR1) contains flux calibrated spectra from the first year (April 2012-2013). A total of 221 confirmed supernovae were classified, and we released calibrated optical spectra and classifications publicly within 24 h of the data being taken (via WISeREP). The data in SSDR1 replace those released spectra. They have more reliable and quantifiable flux calibrations, correction for telluric absorption, and are made available in standard ESO Phase 3 formats. We estimate the absolute accuracy of the flux calibrations for EFOSC2 across the whole survey in SSDR1 to be typically ∼15%, although a number of spectra will have less reliable absolute flux calibration because of weather and slit losses. Acquisition images for each spectrum are available which, in principle, can allow the user to refine the absolute flux calibration. The standard NIR reduction process does not produce high accuracy absolute spectrophotometry but synthetic photometry with accompanying JHK<inf>s</inf> imaging can improve this. Whenever possible, reduced SOFI images are provided to allow this. 

Conclusions. Future data releases will focus on improving the automated flux calibration of the data products. The rapid turnaround between discovery and classification and access to reliable pipeline processed data products has allowed early science papers in the first few months of the survey.

Calvinist Absolutism: Archbishop James Ussher and Royal Power

Archbishop James Ussher's manuscript notebooks allow us to observe the making of a Calvinist absolutist and to orientate the archbishop's beliefs about royal power within European Reformed thought as a whole. By 1643, Ussher was preaching a polished and complete theory of absolute royal power, and it is possible to track the development of this political theory forward from his undergraduate days in the 1590s. Throughout his life Ussher engaged anxiously with Reformed theologians abroad, who generally favored limited rather than absolute monarchy. Nevertheless, Ussher shared with these Reformed colleagues both an antipathy to aspects of Aristotelian politics and a commitment to the divine institution of royal power. Finally, despite Ussher's hostility to Laudian innovations in the Irish Church, his heartfelt political beliefs made him a firm supporter of Stuart absolutism throughout the Three Kingdoms.

Essays on James Clarence Mangan: The Man in the Cloak

This volume explores the extraordinary literary achievement of James Clarence Mangan (1803-1849), increasingly recognised as one of the most important Irish writers of the nineteenth century and a crucial influence on later writers such as W.B. Yeats and James Joyce. It is the first collection of essays to focus on Mangan, and features articles by leading scholars in the field (including Jacques Chuto and David Lloyd) as well as contributions from acclaimed contemporary writers, Paul Muldoon and Ciaran Carson. The collection expands existing fields of debate--translation, the supernatural, intertextuality, nationalism, romanticism-- and introduces new ones: Mangan's afterlife in the English literary canon, cosmopolitanism and Weltliteratur, antiquity and futurity, nineteenth-century spiritualism and magical thinking. 'The man in the cloak', one of Mangan's favourite pseudonyms, is still a a resonant soubriquet for a writer who has eluded sustained critical attention, and this volumes restores him to his proper place in European and British, as well as Irish literary history.

The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis

The androgen receptor (AR) is a key regulator of prostate growth and the principal drug target for the treatment of prostate cancer. Previous studies have mapped AR targets and identified some candidates which may contribute to cancer progression, but did not characterize AR biology in an integrated manner. In this study, we took an interdisciplinary approach, integrating detailed genomic studies with metabolomic profiling and identify an anabolic transcriptional network involving AR as the core regulator. Restricting flux through anabolic pathways is an attractive approach to deprive tumours of the building blocks needed to sustain tumour growth. Therefore, we searched for targets of the AR that may contribute to these anabolic processes and could be amenable to therapeutic intervention by virtue of differential expression in prostate tumours. This highlighted calcium/calmodulin-dependent protein kinase kinase 2, which we show is overexpressed in prostate cancer and regulates cancer cell growth via its unexpected role as a hormone-dependent modulator of anabolic metabolism. In conclusion, it is possible to progress from transcriptional studies to a promising therapeutic target by taking an unbiased interdisciplinary approach.

SN 2011dh: DISCOVERY OF A TYPE IIb SUPERNOVA FROM A COMPACT PROGENITOR IN THE NEARBY GALAXY M51

On 2011 May 31 UT a supernova (SN) exploded in the nearby galaxy M51 (the Whirlpool Galaxy). We discovered this event using small telescopes equipped with CCD cameras and also detected it with the Palomar Transient Factory survey, rapidly confirming it to be a Type II SN. Here, we present multi-color ultraviolet through infrared photometry which is used to calculate the bolometric luminosity and a series of spectra. Our early-time observations indicate that SN 2011dh resulted from the explosion of a relatively compact progenitor star. Rapid shock-breakout cooling leads to relatively low temperatures in early-time spectra, compared to explosions of red supergiant stars, as well as a rapid early light curve decline. Optical spectra of SN 2011dh are dominated by H lines out to day 10 after explosion, after which He I lines develop. This SN is likely a member of the cIIb (compact IIb) class, with progenitor radius larger than that of SN 2008ax and smaller than the eIIb (extended IIb) SN 1993J progenitor. Our data imply that the object identified in pre-explosion Hubble Space Telescope images at the SN location is possibly a companion to the progenitor or a blended source, and not the progenitor star itself, as its radius (~1013 cm) would be highly inconsistent with constraints from our post-explosion spectra.

Young Stellar Object VARiability (YSOVAR): Long Timescale Variations in the Mid-infrared

The YSOVAR (Young Stellar Object VARiability) Spitzer Space Telescope observing program obtained the first extensive mid-infrared (3.6 and 4.5 μm) time series photometry of the Orion Nebula Cluster plus smaller footprints in 11 other star-forming cores (AFGL 490, NGC 1333, Mon R2, GGD 12-15, NGC 2264, L1688, Serpens Main, Serpens South, IRAS 20050+2720, IC 1396A, and Ceph C). There are ~29,000 unique objects with light curves in either or both IRAC channels in the YSOVAR data set. We present the data collection and reduction for the Spitzer and ancillary data, and define the "standard sample" on which we calculate statistics, consisting of fast cadence data, with epochs roughly twice per day for ~40 days. We also define a "standard sample of members" consisting of all the IR-selected members and X-ray-selected members. We characterize the standard sample in terms of other properties, such as spectral energy distribution shape. We use three mechanisms to identify variables in the fast cadence data—the Stetson index, a χ2 fit to a flat light curve, and significant periodicity. We also identified variables on the longest timescales possible of six to seven years by comparing measurements taken early in the Spitzer mission with the mean from our YSOVAR campaign. The fraction of members in each cluster that are variable on these longest timescales is a function of the ratio of Class I/total members in each cluster, such that clusters with a higher fraction of Class I objects also have a higher fraction of long-term variables. For objects with a YSOVAR-determined period and a [3.6]-[8] color, we find that a star with a longer period is more likely than those with shorter periods to have an IR excess. We do not find any evidence for variability that causes [3.6]-[4.5] excesses to appear or vanish within our data set; out of members and field objects combined, at most 0.02% may have transient IR excesses.

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.

The perception of woman on the example of the Odyssey of Homer and its english translation by James Huddleston and portuguese translation by Frederico Lourenço

Dissertação de mestrado, Estudos Literários e Artísticos, Faculdade de Ciências Humanas e Sociais, Universidade do Algarve, 2015