An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss

Background Environmental factors can influence obesity by epigenetic mechanisms. Adipose tissue plays a key role in obesity-related metabolic dysfunction, and gastric bypass provides a model to investigate obesity and weight loss in humans. Results Here, we investigate DNA methylation in adipose tissue from obese women before and after gastric bypass and significant weight loss. In total, 485,577 CpG sites were profiled in matched, before and after weight loss, subcutaneous and omental adipose tissue. A paired analysis revealed significant differential methylation in omental and subcutaneous adipose tissue. A greater proportion of CpGs are hypermethylated before weight loss and increased methylation is observed in the 3′ untranslated region and gene bodies relative to promoter regions. Differential methylation is found within genes associated with obesity, epigenetic regulation and development, such as CETP, FOXP2, HDAC4, DNMT3B, KCNQ1 and HOX clusters. We identify robust correlations between changes in methylation and clinical trait, including associations between fasting glucose and HDAC4, SLC37A3 and DENND1C in subcutaneous adipose. Genes investigated with differential promoter methylation all show significantly different levels of mRNA before and after gastric bypass. Conclusions This is the first study reporting global DNA methylation profiling of adipose tissue before and after gastric bypass and associated weight loss. It provides a strong basis for future work and offers additional evidence for the role of DNA methylation of adipose tissue in obesity.

The performance advantages for SMEs of product innovation and marketing resource–capability complementarity in emerging economies

This study argues that small and medium-sized enterprises (SMEs) must possess both resources and capabilities at a superior level, and those resources and capabilities must be complementary with one another to achieve superior financial performance. The resources and capabilities of interest are product innovation and marketing. Using data from manufacturing SMEs, the results suggest that product innovation resource–capability complementarity, marketing resource–capability complementarity, and their interaction are positively related to financial performance through product innovation and customer performance. The findings suggest that some SMEs may outperform others not only because they possess a specific individual resource–capability complementarity but also because they create synergy and asset interconnectedness.

Growing food in the city : Design ideations for urban residential gardeners

Urban agriculture refers to the production of food in urban and peri-urban spaces. It can contribute positively to health and food security of a city, while also reducing ‘food miles.’ It takes on many forms, from the large and organised community garden, to the small and discrete backyard or balcony. This study focuses on small-scale food production in the form of residential gardening for home or personal use. We explore opportunities to support people’s engagement in urban agriculture via human-computer interaction design. This research presents the findings and HCI design insights from our study of residential gardeners in Brisbane, Australia. By exploring their understanding of gardening practice with a human-centred design approach, we present six key themes, highlighting opportunities and challenges relating to available time and space; the process of learning and experimentation; and the role of existing online platforms to support gardening practice. Finally we discuss the overarching theme of shared knowledge, and how HCI could improve community engagement and gardening practice.

4.2.5 Environmental engineering

Th is landmark report on engineering and development is the fi rst of its kind to be produced by UNESCO, or indeed by any international organization. Containing highly informative and insightful contributions from 120 experts from all over the world, the report gives a new perspective on the very great importance of the engineer’s role in development. Advances in engineering have been central to human progress ever since the invention of the wheel. In the past hundred and fi fty years in particular, engineering and technology have transformed the world we live in, contributing to signifi cantly longer life expectancy and enhanced quality of life for large numbers of the world’s population. Yet improved healthcare, housing, nutrition, transport, communications, and the many other benefi ts engineering brings are distributed unevenly throughout the world. Millions of people do not have clean drinking water and proper sanitation, they do not have access to a medical centre, they may travel many miles on foot along unmade tracks every day to get to work or school...

Advancing nursing practice: The role of the nurse practitioner in an acute stroke program

The Foothills Medical Centre in Calgary, AB, Canada, is a tertiarycare referral center for southern Alberta and southeastern British Columbia. The Calgary Stroke Program, which serves a population of 1.5 million people and a geographic territory of more than 114,233 square kilometers (44,622 square miles), annually offers acute and follow-up care to more than 1,000 people with stroke. Leading the team of healthcare professionals dedicated to providing excellence in stroke patient care is a stroke nurse practitioner (SNP). The nurse practitioner role in Canada, as in many healthcare settings, was initially developed in response to cutbacks in medical residency programs and increasing acuity levels of hospitalized patients (Irvine et al., 2000). This article describes the development of the SNP role and its impact on system and process changes and patient care and outcomes in an acute stroke program in the Calgary Health Region.

Common polygenic variation contributes to risk of migraine in the Norfolk Island population

Migraine has been defined as a common disabling primary headache disorder. Epidemiology studies have provided with the undeniable evidence of genetic components as active players in the development of the disease under a polygenic model in which multiple risk alleles exert modest individual effects. Our objective was to test the contribution of a polygenic effect to migraine risk in the Norfolk Island population using a panel of SNPs reported to be disease associated in published migraine GWAS. We also investigated whether individual SNPs were associated with gene expression levels measured in whole-blood. Polygenic scores were calculated in a total of 285 related individuals (74 cases, 211 controls) from the Norfolk Island using 51 SNPs previously reported to be associated with migraine in published GWAS. The association between polygenic score and migraine case-control status was tested using logistic regression. Results indicate that a migraine polygenic risk score was associated with migraine case-control status in this population (P=0.016). This supports the hypothesis that multiple SNPs with weak effects collectively contribute to migraine risk in this population. Amongst the SNPs included in the polygenic model, 4 were associated with the expression of the USMG5 gene, including rs171251 (P = 0.012). Results from this study provide evidence for a polygenic contribution to migraine risk in an isolated population and highlight specific SNPs that regulate the expression of USMG5, a gene critical for mitochondrial function.

PTHR1 polymorphisms influence BMD variation through effects on the growing skeleton

We investigated whether polymorphisms in PTHR1 are associated with bone mineral density (BMD), to determine whether the association of this gene with BMD was due to effects on attainment of peak bone mass or effects on subsequent bone loss. The PTHR1 gene, including its 14 exons, their exon-intron boundaries, and 1,500 bp of its promoter region, was screened for polymorphisms by denaturing high-performance liquid chromatography (dHPLC) and sequencing in 36 osteoporotic cases. Eleven single-nucleotide polymorphisms (SNPs), one tetranucleotide repeat, and one tetranucleotide deletion were identified. A cohort of 634 families, including 1,236 men (39%) and 1,926 women (61%) ascertained with probands with low BMD (Z< -2.0) and the Children in Focus subset of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (785 unrelated individuals, mean age 118 months), were genotyped for the five most informative SNPs (minor allele frequency >5%) and the tetranucleotide repeat. In our osteoporosis families, association was noted between lumbar spine BMD and alleles of a known functional tetranucleotide repeat (U4) in the PTHR1 promoter region (P = 0.042) and between two and three marker haplotypes of PTHR1 polymorphisms with lumbar spine, femoral neck, and total hip BMD (P = 0.021-0.047). This association was restricted to the youngest tertile of the population (age 16-39 years, P = 0.013-0.048). A similar association was found for the ALSPAC cohort: two marker haplotypes of SNPs A48609T and C52813T were associated with height (P = 0.006) and total body less head BMD (P = 0.02), corrected for age and gender, confirming the family findings. These findings suggest a role for PTHR1 variation in determining peak BMD.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Influence of LRP5 polymorphisms on normal variation in BMD

Genetic studies based on cohorts with rare and extreme bone phenotypes have shown that the LRP5 gene is an important genetic modulator of BMD. Using family-based and case-control approaches, this study examines the role of the LRP5 gene in determining normal population variation of BMD and describes significant association and suggestive linkage between LRP5 gene polymorphisms and BMD in >900 individuals with a broad range of BMD. Introduction: Osteoporosis is a common, highly heritable condition determined by complex interactions of genetic and environmental etiologies. Genetic factors alone can account for 50-80% of the interindividual variation in BMD. Mutations in the LRP5 gene on chromosome 11q12-13 have been associated with rare syndromes characterized by extremely low or high BMD, but little is known about the contribution of this gene to the development of osteoporosis and determination of BMD in a normal population. Materials and Methods: To examine the entire spectrum of low to high BMD, 152 osteoporotic probands, their families (597 individuals), and 160 women with elevated BMD (T score > 2.5) were recruited. BMD at the lumbar spine, femoral neck, and hip were measured in each subject using DXA. Results: PAGE sequencing of the LRP5 gene revealed 10 single nucleotide polymorphisms (SNPs), 8 of which had allele frequencies of >5%, in exons 8, 9, 10, 15, and 18 and in introns 6, 7, and 21. Within families, a strong association was observed between an SNP at nucleotide C171346A in intron 21 and total hip BMD (p < 1 × 10-5 in men only, p = 0.0019 in both men and women). This association was also observed in comparisons of osteoporotic probands and unrelated elevated BMD in women (p = 0.03), along with associations with markers in exons 8 (C135242T, p = 0.007) and 9 (C141759T, p = 0.02). Haplotypes composed of two to three of the SNPs G121513A, C135242T, G138351A, and C141759T were strongly associated with BMD when comparing osteoporotic probands and high BMD cases (p < 0.003). An SNP at nucleotide C165215T in exon 18 was linked to BMD at the lumbar spine, femoral neck, and total hip (parametric LOD scores = 2.8, 2.5, and 2.2 and nonparametric LOD scores = 0.3, 1.1, and 2.2, respectively) but was not genetically associated with BMD variation. Conclusion: These results show that common LRP5 polymorphisms contribute to the determination of BMD in the general population.

A Phenomic Scan of the Norfolk Island Genetic Isolate Identifies a Major Pleiotropic Effect Locus Associated with Metabolic and Renal Disorder Markers

Multiphenotype genome-wide association studies (GWAS) may reveal pleiotropic genes, which would remain undetected using single phenotype analyses. Analysis of large pedigrees offers the added advantage of more accurately assessing trait heritability, which can help prioritise genetically influenced phenotypes for GWAS analysis. In this study we performed a principal component analysis (PCA), heritability (h2) estimation and pedigree-based GWAS of 37 cardiovascular disease -related phenotypes in 330 related individuals forming a large pedigree from the Norfolk Island genetic isolate. PCA revealed 13 components explaining >75% of the total variance. Nine components yielded statistically significant h2 values ranging from 0.22 to 0.54 (P<0.05). The most heritable component was loaded with 7 phenotypic measures reflecting metabolic and renal dysfunction. A GWAS of this composite phenotype revealed statistically significant associations for 3 adjacent SNPs on chromosome 1p22.2 (P<1x10-8). These SNPs form a 42kb haplotype block and explain 11% of the genetic variance for this renal function phenotype. Replication analysis of the tagging SNP (rs1396315) in an independent US cohort supports the association (P = 0.000011). Blood transcript analysis showed 35 genes were associated with rs1396315 (P<0.05). Gene set enrichment analysis of these genes revealed the most enriched pathway was purine metabolism (P = 0.0015). Overall, our findings provide convincing evidence for a major pleiotropic effect locus on chromosome 1p22.2 influencing risk of renal dysfunction via purine metabolism pathways in the Norfolk Island population. Further studies are now warranted to interrogate the functional relevance of this locus in terms of renal pathology and cardiovascular disease risk.

Field evaluation of a plant activator, captan, chlorothalonil, copper hydroxide, iprodione, mancozeb and strobilurins for the control of citrus brown spot of mandarin

Brown spot (caused by Alternaria alternata) is a major disease of citrus in subtropical areas of Australia. A number of chemicals, the strobilurins azoxystrobin, trifloxystrobin, pyraclostrobin and methoxycrylate, a plant activator (acibenzolar), copper hydroxide, mancozeb, captan, iprodione and chlorothalonil/pyrimthanil were tested in the field for its control. Over three seasons, trees in a commercial orchard received 16, 14 and 7 fungicide sprays, respectively, commencing at flowering in the first season, and petal fall in the later seasons. In all experiments, the strobilurins used alone, or incorporated with copper and mancozeb, were as effective as, or better than the industry standard of copper and mancozeb alone. The only exception was trifloxystrobin, which when used alone was less effective than the industry standard. Acibenzolar used alone was ineffective. Applying a mixture of azoxystrobin and acibenzolar was found to reduce the incidence of brown spot compared with applying azoxystrobin alone but, in either case, disease levels were not found to be significantly different to the industry standard. Captan, iprodione and chlorothalonil/pyrimthanil were as effective as the industry standard. The incidence and severity of rind damage were significantly lowest in the azoxystrobin, methoxycrylate, iprodione and chlorothalonil/pyrimthanil treatments. Medium and high rates of trifloxystrobin (0.07 g/L, 0 .15 g/L) and pyraclostrobin (0.8 g/L, 1.2 g/L) applied alone were the only treatments found to be IPM-incompatible as shown by the elevated level of scale infection on fruit.

Timing of fungicide applications for control of husk spot caused by Pseudocercospora macadamiae in macadamia

Pseudocercospora macadamiae is an important pathogen of macadamia in Australia, causing a disease known as husk spot. Growers strive to control the disease with a number of carbendazim and copper treatments. The aim of this study was to consider the macadamia fruit developmental stage at which fungicide application is most effective against husk spot, and whether application of copper-only applications at full-size fruit developmental stage toward the end of the season contributed to effective disease control. Fungicides were applied to macadamia trees at four developmental stages in three orchards in two subsequent production seasons. The effects of the treatments on disease incidence and severity were quantified using area under disease progress curve (AUDPC) and logistic regression models. Although disease incidence varied between cultivars, incidence and severity on cv. A16 showed consistent differences between the treatments. Most significant reduction in husk spot incidence occurred when spraying commenced at match-head sized-fruit developmental stage. All treatments significantly reduced husk spot incidence and severity compared with the untreated controls, and a significant positive linear relationship (R2 = 73%) between AUDPC and severity showed that timing of the first fungicide application is important for effective disease control. Application of fungicide at full-size fruit stage reduced disease incidence but had no impact on premature fruit drop.

Alternative fungicides for controlling husk spot caused by Pseudocercospora macadamiae in macadamia

Husk spot, caused by Pseudocercospora macadamiae is a major fungal disease of macadamia in Australia. Chemicals to control the disease are limited and frequent failure to control the disease is a major concern to growers. The overall goal of this research was to improve the chemical control strategy of P. macadamiae through the provision of fungicides with different modes of action to carbendazim, which is the current industry standard. Husk spot incidence, premature fruit abscission, kernel quality and yield were evaluated following application of different fungicide products in replicated field experiments at three different sites. Results showed significant differences in disease incidence and premature fruit abscission between fungicide treatments, field sites and years. Generally, disease incidence and premature fruit abscission on trees treated with fungicide were significantly (P < 0.05) lower than the untreated control. Pyraclostrobin conferred significantly better protection than trifloxystrobin, reducing disease severity by 70% compared with a 50% reduction by trifloxystrobin. The pyraclostrobin treatment had a similar efficacy to the current industry standard (70% reduction cf. 73% reduction by tank-mixed carbendazim and copper). Higher amounts of immature kernels occurred in the untreated control, followed by difenoconazole and trifloxystrobin. Diseased fruit accounted for 78% of premature fruit abscission, which indicates that husk spot enhances fruit abscission in macadamia. Our results suggest that pyraclostrobin provided similar efficacy to the industry standard and could, therefore, play a key role in the management of husk spot.

Svengi ja groove rytmimusiikissa : Rytmiikkaan ja hienorytmiikkaan keskittyvä vertaileva musiikkianalyysi

Käsitteillä svengi ja groove viitataan useimmiten kappaleen tietyn tulkinnan eli esityksen pääasiallisesti rytmisten ominaisuuksien laatuun. Tutkimuksen tavoitteena on kehittää musiikin rytmiikkaan ja hienorytmiikkaan keskittyviä musiikkikognitiivisia analyysimetodeja, joita soveltamalla nämä ominaisuudet voitaisiin tavoittaa. Käsitteiden monitulkintaisuus, joka tuodaan esiin tutkimuksen alussa aiheuttaa tälle monenlaisia haasteita. -- Tutkimuksen rytmiikkaan keskittyviä analyysimetodeja sovellettaessa musiikkia tarkastellaan tietystä esityksestä tehdyn nuottiesityksen, transkription välityksellä. Hienorytmisiä analyysimetodeja käytettäessä musiikkia tarkastellaan esitysten instrumenttiosuuksien sävelten alukehetkien tarkkojen sijaintien kautta. Alukehetket poimitaan erilaisin automaattisin ja manuaalisin tietokoneavusteisin menetelmin äänitteiltä. Tutkimuksessa tarkastellaan musiikissa esiintyviä ilmiöitä myös laajemmalla, musiikin havaitsemiseen ja tuottamiseen yleisesti liittyvällä musiikkikognition tasolla. Tärkeänä näkökulmana musiikin rytmiikan esitetään jakautuvan kognitiivisesti karkeampaan tekstuaaliseen rytmiikkaan ja tätä hienoisesti varioivaan ei-tekstuaaliseen hienorytmiikkaan. Analyysiosuudessa kehitettyjä metodeja sovelletaan seuraavien kappaleiden soolo-osuuksiin: Miles Davis – 'Freddie Freeloader' (1959), James Brown – 'Doing it to Death' (1973) ja Led Zeppelin – 'Stairway to Heaven' (1971). Kappaleet edustavat tutkimuksessa jazz-, funk- ja rock-tyylilajeja. Analyysi tarkastelee ja vertailee kappaleiden metristä stabiiliutta, instrumenttiosuuksien suhdetta pulssin iskuihin, rytmiikan kolmimuunteisuutta, soolojen metrisiä painopisteitä, soolojen rytmistä tiheyttä sekä tempojen muutoksia. -- Kehitetyt menetelmät osoittautuvat kaikki käyttökelpoisiksi. Kappaleille yhteiseksi piirteeksi paljastuu instrumenttiosuuksien säännönmukainen sijoittuminen pulssin iskuihin nähden kappaleiden sisällä. Kappaleiden välillä eri instrumentit sijoittuvat kuitenkin pulssin ympärille eroavin tavoin, jonka oletetaan johtuvan ennen kaikkea tyylilajien eroista. Tempot pysyvät kappaleissa varsin muuttumattomina. Jatkotutkimuksen kannalta mielenkiintoisia näkymiä ovat muun muassa metodien laajempi soveltaminen, automaattisten menetelmien kehittäminen

Vapaata mielenjuoksua : Suomenkielisen freestyle-rapin ilmenemismuodot, estetiikka ja kompositio

The thesis is about Finnish freestyle-rap, a modern form of oral poetry producing improvised rap lyrics at the moment of performance. The research material consists of interviews with seven freestyle experts and a DVD from Finnish Rap Championships 2005 containing freestyle-rap. The thesis has three goals: describing the different variations or subgenres of freestyle, outlining the esthetics and register of freestyle, and examining the composition of freestyle. The research material acts a central role in the thesis but the theoretical framework is also wide: cornerstones are John Miles Foley's register analysis, oral formulaic theory and William Levelt's psycholinguistic theory on planning of speech. Freestyle is divided into three partially overlapping genres with slight variation in conventions. The genres are freestyle battle, cypher, and live freestyle. Freestyle's esthetics are composed of certain qualities and preferences: the rhyme is a syllabically repeating vocal rhyme. The rapping must be synchronised with the background rhythm and the rhyme comes in the end of the line. The lyrics must be somehow anchored to the surroundings and the moment of performance. The style of rapping, ie. flow, has to be personal one way or the other. Individual formulas are used to some extent in freestyle compostition. When planning the lines, all other content is subordinate to the rhyme, whose phonetic processing is the primary act in the planning of freestyle. This discovery sets Levelt's theory open to doubt.