418 research outputs found
Psychometric properties of the Self-Esteem Questionnaire for South African adolescents
This article describes two studies investigating the reliability and factorial validity of scores on the Self-Esteem Questionnaire (SEQ) for assessing self-evaluations relating to peers, school, family, sports/athletics, body image and global self-worth in South African adolescents. Participants were 900 learners enrolled in Grades 8 and 11 at public schools in Cape Town, and 116 Grades 8 and 11 learners attending independent schools. The results provided general support for the six-factor structure proposed by DuBois, Felner, Brand, Phillips and Lease (1996) and indicated that SEQ scores have good internal consistency and adequate test-retest reliability for English-speaking South Africans. However, minor revisions are needed for all scale scores to have acceptable internal consistency when translated into isiXhosa or Afrikaans
A global climatological model of extreme geomagnetic field fluctuations
This paper presents a multi-parameter global statistical model of extreme horizontal geomagnetic field fluctuations (dBH/dt), which are a useful input to models assessing the risk of geomagnetically induced currents in ground infrastructure. Generalised Pareto (GP) distributions were fitted to 1-min measurements of |dBH/dt| from 125 magnetometers (with an average of 28 years of data per site) and return levels (RL) predicted for return periods (RP) between 5 and 500 years. Analytical functions characterise the profiles of maximum-likelihood GP model parameters and the derived RLs as a function of corrected geomagnetic latitude, λ. A sharp peak in both the GP shape parameter and the RLs is observed at |λ| = 53° in both hemispheres, indicating a sharp equatorward limit of the auroral electrojet region. RLs also increase strongly in the dayside region poleward of the polar cusp (|λ| > 75°) for RPs > 100 years. We describe how the GP model may be further refined by modelling the probability of occurrences of |dBH/dt| exceeding the 99.97th percentile as a function of month, magnetic local time, and the direction of the field fluctuation, dBH, and demonstrate that these patterns of occurrence align closely to known patterns of auroral substorm onsets, ULF Pc5 wave activity, and (storm) sudden commencement impacts. Changes in the occurrence probability profiles with the interplanetary magnetic field (IMF) orientation reveal further details of the nature of the ionospheric currents driving extreme |dBH/dt| fluctuations, such as the changing location of the polar cusp and seasonal variations explained by the Russell-McPherron effect
A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion
Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al
Localising Loci underlying Complex Trait Variation Using Regional Genomic Relationship Mapping
The limited proportion of complex trait variance identified in genome-wide association studies may reflect the limited power of single SNP analyses to detect either rare causative alleles or those of small effect. Motivated by studies that demonstrate that loci contributing to trait variation may contain a number of different alleles, we have developed an analytical approach termed Regional Genomic Relationship Mapping that, like linkage-based family methods, integrates variance contributed by founder gametes within a pedigree. This approach takes advantage of very distant (and unrecorded) relationships, and this greatly increases the power of the method, compared with traditional pedigree-based linkage analyses. By integrating variance contributed by founder gametes in the population, our approach provides an estimate of the Regional Heritability attributable to a small genomic region (e.g. 100 SNP window covering ca. 1 Mb of DNA in a 300000 SNP GWAS) and has the power to detect regions containing multiple alleles that individually contribute too little variance to be detectable by GWAS as well as regions with single common GWAS-detectable SNPs. We use genome-wide SNP array data to obtain both a genome-wide relationship matrix and regional relationship (“identity by state" or IBS) matrices for sequential regions across the genome. We then estimate a heritability for each region sequentially in our genome-wide scan. We demonstrate by simulation and with real data that, when compared to traditional (“individual SNP") GWAS, our method uncovers new loci that explain additional trait variation. We analysed data from three Southern European populations and from Orkney for exemplar traits – serum uric acid concentration and height. We show that regional heritability estimates are correlated with results from genome-wide association analysis but can capture more of the genetic variance segregating in the population and identify additional trait loci
The star formation histories of galaxies in the Sloan Digital Sky Survey
We present the results of a MOPED analysis of ~3 x 10^5 galaxy spectra from
the Sloan Digital Sky Survey Data Release Three (SDSS DR3), with a number of
improvements in data, modelling and analysis compared with our previous
analysis of DR1. The improvements include: modelling the galaxies with
theoretical models at a higher spectral resolution of 3\AA; better calibrated
data; an extended list of excluded emission lines, and a wider range of dust
models. We present new estimates of the cosmic star formation rate, the
evolution of stellar mass density and the stellar mass function from the fossil
record. In contrast to our earlier work the results show no conclusive peak in
the star formation rate out to a redshift around 2 but continue to show
conclusive evidence for `downsizing' in the SDSS fossil record. The star
formation history is now in good agreement with more traditional instantaneous
measures. The galaxy stellar mass function is determined over five decades of
mass, and an updated estimate of the current stellar mass density is presented.
We also investigate the systematic effects of changes in the stellar population
modelling, the spectral resolution, dust modelling, sky lines, spectral
resolution and the change of data set. We find that the main changes in the
results are due to the improvements in the calibration of the SDSS data,
changes in the initial mass function and the theoretical models used.Comment: replaced to match accepted version in MNRA
Galaxy Pairs in the Sloan Digital Sky Survey - III: Evidence of Induced Star Formation from Optical Colours
We have assembled a large, high quality catalogue of galaxy colours from the
Sloan Digital Sky Survey Data Release 7, and have identified 21,347 galaxies in
pairs spanning a range of projected separations (r_p < 80 h_{70}^{-1} kpc),
relative velocities (\Delta v < 10,000 km/s, which includes projected pairs
that are essential for quality control), and stellar mass ratios (from 1:10 to
10:1). We find that the red fraction of galaxies in pairs is higher than that
of a control sample matched in stellar mass and redshift, and demonstrate that
this difference is likely due to the fact that galaxy pairs reside in higher
density environments than non-paired galaxies. We detect clear signs of
interaction-induced star formation within the blue galaxies in pairs, as
evidenced by a higher fraction of extremely blue galaxies, along with blueward
offsets between the colours of paired versus control galaxies. These signs are
strongest in close pairs (r_p < 30 h_{70}^{-1} kpc and \Delta v < 200 km/s),
diminish for more widely separated pairs (r_p > 60 h_{70}^{-1} kpc and \Delta v
< 200 km/s) and disappear for close projected pairs (r_p < 30 h_{70}^{-1} kpc
and \Delta v > 3000 km/s). These effects are also stronger in central (fibre)
colours than in global colours, and are found primarily in low- to
medium-density environments. Conversely, no such trends are seen in red
galaxies, apart from a small reddening at small separations which may result
from residual errors with photometry in crowded fields. When interpreted in
conjunction with a simple model of induced starbursts, these results are
consistent with a scenario in which close peri-centre passages trigger induced
star formation in the centres of galaxies which are sufficiently gas rich,
after which time the galaxies gradually redden as they separate and their
starbursts age.Comment: 17 pages. Accepted for publication in MNRA
Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin
Background:
Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties.
Methodology/Results:
The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface.
Conclusion:
Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1
Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica.
Control of liver fluke infections remains a significant challenge in the livestock sector due to widespread distribution of drug resistant parasite populations. In particular, increasing prevalence and economic losses due to infection with Fasciola hepatica is a direct result of drug resistance to the gold standard flukicide, triclabendazole. Sustainable control of this significant zoonotic pathogen, therefore, urgently requires the identification of new anthelmintics. Plants represent a source of molecules with potential flukicidal effects and, amongst their secondary metabolites, the diterpenoid abietic acids can be isolated in large quantities. In this study, nineteen (19) chemically modified abietic acid analogues (MC_X) were first evaluated for their anthelmintic activities against F. hepatica newly excysted juveniles (NEJs, from the laboratory-derived Italian strain); from this, 6 analogues were secondly evaluated for their anthelmintic activities against adult wild strain flukes. One analogue, MC010, was progressed further against 8-week immature- and 12-week mature Italian strain flukes. Here, MC010 demonstrated moderate activity against both of these intra-mammalian fluke stages (with an adult fluke EC50 = 12.97 µM at 72 h post culture). Overt mammalian cell toxicity of MC010 was inferred from the Madin-Darby bovine kidney (MDBK) cell line (CC50 = 17.52 µM at 24 h post culture) and demonstrated that medicinal chemistry improvements are necessary before abietic acid analogues could be considered as potential anthelmintics against liver fluke pathogen
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