952 research outputs found
Quantifying land surface temperature variability for two Sahelian mesoscale regions during the wet season
Land-atmosphere feedbacks play an important role in the weather and climate of many semi-arid regions. These feedbacks are strongly controlled by how the surface responds to precipitation events, which regulate the return of heat and moisture to the atmosphere. Characteristics of the surface can result in both differing amplitudes and rates of warming following rain. We used spectral analysis to quantify these surface responses to rainfall events using land surface temperature (LST) derived from Earth Observations (EO). We analysed two mesoscale regions in the Sahel and identified distinct differences in the strength of the short-term (< 5–day) spectral variance, notably a shift towards lower frequency variability in forest pixels relative to non-forest areas, and an increase in amplitude with decreasing vegetation cover. Consistent with these spectral signatures, we found that areas of forest, and to a lesser extent grassland regions, warm up more slowly than sparsely vegetated or barren pixels. We applied the same spectral analysis method to simulated LST data from the the Joint UK Land Environment Simulator (JULES) land surface model. We found a reasonable level of agreement with the EO spectral analysis, for two contrasting land surface regions. However JULES shows a significant underestimate in the magnitude of the observed response to rain compared to EO. A sensitivity analysis of the JULES model highlights an unrealistically high level of soil water availability as a key deficiency, which dampens the models response to rainfall events
Structure and play: rethinking regulation in the higher education sector
This paper explores possible tactics for academics working within a context of increasing regulation and constraint. One suggested tactic is to move outside of a creativity-conformity binary. Rather than understanding creativity and conformity as separable, where one is seen as excluding the other, the authors consider the potential of examining the relationships between them. The theme of 'structure and play' illustrates the argument. In the first part of the paper, using various examples from art and design - fields generally associated with creativity - the authors explore the interrelatedness of creativity and conformity. For example, how might design styles, which are generally understood as creative outcomes, constrain creativity and lead to conformity within the design field? Is fashion producing creativity or conformity? Conversely, the ways in which conformity provides the conditions for creativity are also examined. For example, the conformity imposed by the state on artists in the former communist bloc contributed to a thriving underground arts movement which challenged conformity and state regulation. Continuing the theme of 'structure and play', the authors recount a story from an Australian university which foregrounds the ongoing renegotiation of power relations in the academy. This account illustrates how programmatic government in a university, with its aim of regulating conduct, can contribute to unanticipated outcomes. The authors propose that a Foucauldian view of distributed power is useful for academics operating in a context of increasing regulation, as it brings into view sites where power might begin to be renegotiated
Type 2 Diabetes Risk Alleles Are Associated With Reduced Size at Birth
OBJECTIVE: Low birth weight is associated with an increased risk of type 2 diabetes. The mechanisms underlying this association are unknown and may represent intrauterine programming or two phenotypes of one genotype. The fetal insulin hypothesis proposes that common genetic variants that reduce insulin secretion or action may predispose to type 2 diabetes and also reduce birth weight, since insulin is a key fetal growth factor. We tested whether common genetic variants that predispose to type 2 diabetes also reduce birth weight. RESEARCH DESIGN AND METHODS: We genotyped single-nucleotide polymorphisms (SNPs) at five recently identified type 2 diabetes loci (CDKAL1, CDKN2A/B, HHEX-IDE, IGF2BP2, and SLC30A8) in 7,986 mothers and 19,200 offspring from four studies of white Europeans. We tested the association between maternal or fetal genotype at each locus and birth weight of the offspring. RESULTS: We found that type 2 diabetes risk alleles at the CDKAL1 and HHEX-IDE loci were associated with reduced birth weight when inherited by the fetus (21 g [95% CI 11-31], P = 2 x 10(-5), and 14 g [4-23], P = 0.004, lower birth weight per risk allele, respectively). The 4% of offspring carrying four risk alleles at these two loci were 80 g (95% CI 39-120) lighter at birth than the 8% carrying none (P(trend) = 5 x 10(-7)). There were no associations between birth weight and fetal genotypes at the three other loci or maternal genotypes at any locus. CONCLUSIONS: Our results are in keeping with the fetal insulin hypothesis and provide robust evidence that common disease-associated variants can alter size at birth directly through the fetal genotype
Multilingual gendered identities: female undergraduate students in London talk about heritage languages
In this paper I explore how a group of female university students, mostly British Asian and in their late teens and early twenties, perform femininities in talk about heritage languages. I argue that analysis of this talk reveals ways in which the participants enact ‘culturally intelligible’ gendered subject positions. This frequently involves negotiating the norms of ‘heteronormativity’, constituting femininity in terms of marriage, motherhood and maintenance of heritage culture and language, and ‘girl power’, constituting femininity in terms of youth, sassiness, glamour and individualism. For these young women, I ask whether higher education can become a site in which they have the opportunities to explore these identifications and examine other ways of imagining the self and what their stories suggest about ‘doing being’ a young British Asian woman in London
Rethinking the ‘aspirations’ of Chinese girls within and beyond Health and Physical Education and physical activity in Greater Western Sydney
This paper aims to explore young Chinese girls’ aspirations and ideal environments for engagement in Health and Physical Education (HPE) and physical activity (PA) in Greater Western Sydney. Interviews are used to elicit these girls’ perceptions of their future and ideal environments in relation to HPEPA. Their data offer insights into key influences regarding what is thinkable, desirable and achievable in their HPEPA environments. Results showed dimensions of environments, such as social and pedagogical aspects, that are conducive to these girls’ aspirations in HPEPA (e.g. social support from parents, and functional built environment for HPE). This paper aligns with a strengths-based approach to understanding and recognising young Chinese girls’ perceived aspirations within their socio-cultural environment. In doing so, we discuss how feminism and femininity are positioned from a Chinese perspective that may provide alternative views to a post-feminist panorama in promoting advancement of all young girls in HPEPA. Results invite us to take into account some of the girls’ ambivalence towards being an ‘autonomous’ and ‘dependent’ modern Chinese young girl. This paper calls for a rethinking of how aspirations that shape young people’s future in HPEPA in much of the contemporary Western world are conceptualised in academic research
Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity
The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature
<p>Abstract</p> <p>Background</p> <p>Human height is considered highly heritable and correlated with certain disorders, such as type 2 diabetes and cancer. Despite environmental influences, genetic factors are known to play an important role in stature determination. A number of genetic determinants of adult height have already been established through genome wide association studies.</p> <p>Methods</p> <p>To examine 51 single nucleotide polymorphisms (SNPs) corresponding to the 46 previously reported genomic loci for height in 8,184 European American children with height measurements. We leveraged genotyping data from our ongoing GWA study of height variation in children in order to query the 51 SNPs in this pediatric cohort.</p> <p>Results</p> <p>Sixteen of these SNPs yielded at least nominally significant association to height, representing fifteen different loci including <it>EFEMP1-PNPT1, GPR126, C6orf173, SPAG17</it>, Histone class 1, HLA class III and <it>GDF5-UQCC</it>. Other loci revealed no evidence for association, including <it>HMGA1 and HMGA2</it>. For the 16 associated variants, the genotype score explained 1.64% of the total variation for height z-score.</p> <p>Conclusion</p> <p>Among 46 loci that have been reported to associate with adult height to date, at least 15 also contribute to the determination of height in childhood.</p
An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy
This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.DNA polymerase δ, whose catalytic subunit is encoded by POLD1, is responsible for lagging-strand DNA synthesis during DNA replication. It carries out this synthesis with high fidelity owing to its intrinsic 3'- to 5'-exonuclease activity, which confers proofreading ability. Missense mutations affecting the exonuclease domain of POLD1 have recently been shown to predispose to colorectal and endometrial cancers. Here we report a recurring heterozygous single-codon deletion in POLD1 affecting the polymerase active site that abolishes DNA polymerase activity but only mildly impairs 3'- to 5'-exonuclease activity. This mutation causes a distinct multisystem disorder that includes subcutaneous lipodystrophy, deafness, mandibular hypoplasia and hypogonadism in males. This discovery suggests that perturbing the function of the ubiquitously expressed POLD1 polymerase has unexpectedly tissue-specific effects in humans and argues for an important role for POLD1 function in adipose tissue homeostasis.This work was supported by NIHR Exeter Clinical Research Facility through funding for SE and ATH and general
infrastructure. The authors thank Michael Day, Annet Damhuis and Richard Gilbert for technical assistance. We
thank Karen Knapp for providing the data for the DEXA calculations. SE, ATH, SO are supported by Wellcome
Weedon et al. Page 6
Nat Genet. Author manuscript; available in PMC 2014 February 01.
Europe PMC Funders Author Manuscripts Europe PMC Funders Author Manuscripts
Trust Senior Investigator awards. DS and RKS (098498/Z/12/Z) are supported by Wellcome Trust Senior Research
Fellowships in Clinical Science. MNW is supported by the Wellcome Trust as part of the WT Biomedical
Informatics Hub funding. RO is supported by Diabetes UK. DS, RKS and SO are supported by the UK National
Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. KJG is supported by the Agency for
Science, Technology and Research, Singapore (A*STAR). LAL and MJP are supported by grants NCI-61-6845 and
62-4860
A genome-wide association study identifies protein quantitative trait loci (pQTLs)
There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al
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