345 research outputs found
Genetic sequences of hormone response elements share similarity with predicted alpha helices within DNA binding domains of steroid receptor proteins: A basis for site-specific recognition
AbstractThe 150 amino acid sequence comprising the DNA binding region of rat glucocorticoid receptor protein, RGRDBR, was compared to amino acid sequences of members of the superfamily of eukaryotic DNA regulatory proteins. Maximal similarity fell within the 86 amino acid sequence of RGRDBR reported to contain both DNA binding and transcription regulating properties and within the reported DNA binding regions of those proteins to which it was compared. Chou-Fasman secondary structure predictions within these DNA binding domains revealed a conserved alpha helix-beta turn-alpha helix motif. The 450 nucleotide sequence comprising the complementary DNA (cDNA) of amino acids making up RGRDBR was compared to a nucleotide sequence (â312 to â38) from mouse mammary tumor virus 5âČ long terminal repeat, MMTV5LTR, known to contain glucocorticoid response elements (GREs). The maximally similar subsequence was found within the coding region for predicted alpha helix B of RGRDBR (nucleotides 1376 to 1412) and within a reported GRE of MMTV5LTR (nucleotides â199 to â131). This MMTV5LTR GRE sequence contains an imperfect palindrome of TGTTCT which is the specific recognition motif for DNA binding by both glucocorticoid and progesterone receptors. Since there are multiple coding possibilities for the majority of the 20 known amino acids, the exceptions being methionine and tryptophan which have a single codon, to thoroughly investigate the extent of genetic information conserved between RGRDBR and GRE, we converted this MMTV5LTR GRE nucleotide subsequence (â199 to â131) to amino acids in all three reading frames reading rightward and leftward in both strands. This procedure revealed all coding possibilities within the MMTV5LTR nucleotide subsequence, as well as the location of the codon sites. A comparison of these MMTV5LTR amino acid coding possibilities to RGRDBR predicted helix B amino acids revealed highly conserved genetic information localized within the GRE half-sites, predominantly in the right half-site containing the TGTTCT sequence. In the absence of atomic coordinates for eukaryotic DNA regulatory proteins, a computer model of a eukaryotic/procaryotic hybrid protein was created with RGRDBR predicted helix B replacing helix of F of E. coli cAMP-dependent regulatory protein (CRP) for which coordinates from X-ray crystallography were available. This hybrid protein was docked onto MMTV5LTR at the region of maximal similarity to helix B. Our computer model shows that the side chains of amino acids within RGRDBR helix B are oriented toward, and appear to be capable of interacting with, nucleotides on both strands of their respective codons within a functional GRE. Calculations of H-bonding in this model indicate that amino acids of helix B are forming H-bonds with nucleotides of their cognate codon/anti-codon sites within the major grooves of the GRE half-sites
Are there prehistoric shell middens on Rottwest Island?
In August 1973 a number of different types of shell bed were observed at Rottnest Island. The most massive of these were seen around the lakes at the eastern end of the island and there is no doubt that these are natural marine shell beds. However elsewhere shelly deposits were seen whose origin we could not determine with certainty. A number of midden like lenses of shell were exposed in road sections, particularly along the north side of the island. All of these deposits displayed some of the characteristics of Aboriginal shell middens
IceCube - the next generation neutrino telescope at the South Pole
IceCube is a large neutrino telescope of the next generation to be
constructed in the Antarctic Ice Sheet near the South Pole. We present the
conceptual design and the sensitivity of the IceCube detector to predicted
fluxes of neutrinos, both atmospheric and extra-terrestrial. A complete
simulation of the detector design has been used to study the detector's
capability to search for neutrinos from sources such as active galaxies, and
gamma-ray bursts.Comment: 8 pages, to be published with the proceedings of the XXth
International Conference on Neutrino Physics and Astrophysics, Munich 200
Quantifying Between-Cohort and Between-Sex Genetic Heterogeneity in Major Depressive Disorder
Major depressive disorder (MDD) is clinically heterogeneous with prevalence rates twice as high in women as in men. There are many possible sources of heterogeneity in MDD most of which are not measured in a sufficiently comparable way across study samples. Here, we assess genetic heterogeneity based on two fundamental measures, between-cohort and between-sex heterogeneity. First, we used genome-wide association study (GWAS) summary statistics to investigate between-cohort genetic heterogeneity using the 29 research cohorts of the Psychiatric Genomics Consortium (PGC; N cases = 16,823, N controls = 25,632) and found that some of the cohort heterogeneity can be attributed to ascertainment differences (such as recruitment of cases from hospital vs community sources). Second, we evaluated between-sex genetic heterogeneity using GWAS summary statistics from the PGC, Kaiser Permanente GERA, UK Biobank and the Danish iPSYCH studies but did not find convincing evidence for genetic differences between the sexes. We conclude that there is no evidence that the heterogeneity between MDD data sets and between sexes reflects genetic heterogeneity. Larger sample sizes with detailed phenotypic records and genomic data remain the key to overcome heterogeneity inherent in assessment of MDD
Cohort profile: the Australian genetics of depression study
PURPOSE:Depression is the most common psychiatric disorder and the largest contributor to global disability. The Australian Genetics of Depression study was established to recruit a large cohort of individuals who have been diagnosed with depression at some point in their lifetime. The purpose of establishing this cohort is to investigate genetic and environmental risk factors for depression and response to commonly prescribed antidepressants. PARTICIPANTS:A total of 20â689 participants were recruited through the Australian Department of Human Services and a media campaign, 75% of whom were female. The average age of participants was 43 years±15 years. Participants completed an online questionnaire that consisted of a compulsory module that assessed self-reported psychiatric history, clinical depression using the Composite Interview Diagnostic Interview Short Form and experiences of using commonly prescribed antidepressants. Further voluntary modules assessed a wide range of traits of relevance to psychopathology. Participants who reported they were willing to provide a DNA sample (75%) were sent a saliva kit in the mail. FINDINGS TO DATE:95% of participants reported being given a diagnosis of depression by a medical practitioner and 88% met the criteria for a lifetime depressive episode. 68% of the sample report having been diagnosed with another psychiatric disorder in addition to depression. In line with findings from clinical trials, only 33% of the sample report responding well to the first antidepressant they were prescribed. FUTURE PLANS:A number of analyses to investigate the genetic architecture of depression and common comorbidities will be conducted. The cohort will contribute to the global effort to identify genetic variants that increase risk to depression. Furthermore, a thorough investigation of genetic and psychosocial predictors of antidepressant response and side effects is planned.Enda M Byrne, Katherine M Kirk, Sarah E Medland, John J McGrath, Lucia Colodro-Conde, Richard Parker ... et al
Sensitivity of the IceCube Detector to Astrophysical Sources of High Energy Muon Neutrinos
We present the results of a Monte-Carlo study of the sensitivity of the
planned IceCube detector to predicted fluxes of muon neutrinos at TeV to PeV
energies. A complete simulation of the detector and data analysis is used to
study the detector's capability to search for muon neutrinos from sources such
as active galaxies and gamma-ray bursts. We study the effective area and the
angular resolution of the detector as a function of muon energy and angle of
incidence. We present detailed calculations of the sensitivity of the detector
to both diffuse and pointlike neutrino emissions, including an assessment of
the sensitivity to neutrinos detected in coincidence with gamma-ray burst
observations. After three years of datataking, IceCube will have been able to
detect a point source flux of E^2*dN/dE = 7*10^-9 cm^-2s^-1GeV at a 5-sigma
significance, or, in the absence of a signal, place a 90% c.l. limit at a level
E^2*dN/dE = 2*10^-9 cm^-2s^-1GeV. A diffuse E-2 flux would be detectable at a
minimum strength of E^2*dN/dE = 1*10^-8 cm^-2s^-1sr^-1GeV. A gamma-ray burst
model following the formulation of Waxman and Bahcall would result in a 5-sigma
effect after the observation of 200 bursts in coincidence with satellite
observations of the gamma-rays.Comment: 33 pages, 13 figures, 6 table
Context, Complexity and Contestation: Birmingham's Agreed Syllabuses for Religious Education since the 1970s
publication-status: AcceptedThis is an Author's Original Manuscript of an article whose final and definitive form, the Version of Record, has been published in the Journal of Beliefs and Values, September 2011. Available online at: http://www.tandfonline.com/ or DOI: 10.1080/13617672.2011.600823The present article offers an historical perspective on the 1975, 1995 and 2007 Birmingham Agreed Syllabuses for Religious Education.âIt draws upon historical evidence uncovered as part of âThe hidden history of curriculum change in religious education in English schools, 1969â1979â project, and curriculum history theories, especially David Labareeâs observations about the distance between the ârhetoricalâ and âreceivedâ curricula. We argue that, contrary to the existing historiography, curriculum change in religious education (RE) has been evolutionary not revolutionary. Multiple reasons are posited to explain this, not least among which is the capacity and agency of teachers. Furthermore, we argue that ongoing debates about the nature and purpose of RE, as exemplified in the Birmingham context, reflect the multiple expectations that religious educators and other stakeholders had, and continue to have, of the curriculum subject. These debates contribute to the inertia evident in the implementation of RE curriculum reforms. A consciousness of the history of RE enables curriculum contestations to be contextualised and understood, and, thereby, provides important insights which can be applied to ongoing and future debates and developments
On the selection of AGN neutrino source candidates for a source stacking analysis with neutrino telescopes
The sensitivity of a search for sources of TeV neutrinos can be improved by
grouping potential sources together into generic classes in a procedure that is
known as source stacking. In this paper, we define catalogs of Active Galactic
Nuclei (AGN) and use them to perform a source stacking analysis. The grouping
of AGN into classes is done in two steps: first, AGN classes are defined, then,
sources to be stacked are selected assuming that a potential neutrino flux is
linearly correlated with the photon luminosity in a certain energy band (radio,
IR, optical, keV, GeV, TeV). Lacking any secure detailed knowledge on neutrino
production in AGN, this correlation is motivated by hadronic AGN models, as
briefly reviewed in this paper.
The source stacking search for neutrinos from generic AGN classes is
illustrated using the data collected by the AMANDA-II high energy neutrino
detector during the year 2000. No significant excess for any of the suggested
groups was found.Comment: 43 pages, 12 figures, accepted by Astroparticle Physic
All-particle cosmic ray energy spectrum measured with 26 IceTop stations
We report on a measurement of the cosmic ray energy spectrum with the IceTop
air shower array, the surface component of the IceCube Neutrino Observatory at
the South Pole. The data used in this analysis were taken between June and
October, 2007, with 26 surface stations operational at that time, corresponding
to about one third of the final array. The fiducial area used in this analysis
was 0.122 km^2. The analysis investigated the energy spectrum from 1 to 100 PeV
measured for three different zenith angle ranges between 0{\deg} and 46{\deg}.
Because of the isotropy of cosmic rays in this energy range the spectra from
all zenith angle intervals have to agree. The cosmic-ray energy spectrum was
determined under different assumptions on the primary mass composition. Good
agreement of spectra in the three zenith angle ranges was found for the
assumption of pure proton and a simple two-component model. For zenith angles
{\theta} < 30{\deg}, where the mass dependence is smallest, the knee in the
cosmic ray energy spectrum was observed between 3.5 and 4.32 PeV, depending on
composition assumption. Spectral indices above the knee range from -3.08 to
-3.11 depending on primary mass composition assumption. Moreover, an indication
of a flattening of the spectrum above 22 PeV were observed.Comment: 38 pages, 17 figure
- âŠ