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...

Generalizability of established prostate cancer risk variants in men of African ancestry

Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs116041037 (p = 3.7 × 10(-26) ) and rs6983561 (p = 1.1 × 10(-16) ) at 8q24, as well as rs7210100 (p = 5.4 × 10(-8) ) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p < 0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR) = 1.12, p = 7.3 × 10(-98) ]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.

Tule, rakkaani! : Naisen ja miehen välisestä etiikasta kirjallisuuden rakkauskuvauksissa

Tutkin väitöskirjassani naisen ja miehen välistä rakkautta ja naisen ja miehen välisen rakkauden kuvauksia kirjallisuudessa ranskalaisen filosofin Luce Irigarayn samuuden järjestyksen kritiikin ja sukupuolieron etiikan valossa. Osoitan ensinnäkin, kuinka Platonin Pidoissa, Percy Bysshe Shelleyn Epipsychidionissa (1821) ja Barbara Cartlandin Liekehtivässä lumessa (1975) kuvataan rakkautta kahden rakastavaisen yhteensulautumiseksi - tutkin millaisia haltuunottamisen ja sulauttamisen muotoja rakastavaisten välillä näissä teoksissa tulee esille. Toiseksi osoitan, kuinka Laulujen laulussa, Dian kreivittären 1100-luvulla kirjoittamassa lyriikassa ja Guillevicin runokokoelmasta Trouées (1981) löytyvässä sikermässä Ylistyslaulu kuvataan rakkautta kahden toisiinsa palautumattoman rakastavaisen väliseksi suhteeksi - syvennyn näistä teoksista löytyviin kuvauksiin toista ihmettelevästä kohtaamisesta, toisen huomioonottavasta puhuttelemisesta ja toista hyväilevästä koskettamisesta. Tutkimukseni keskiössä on siis rakastavaisten välinen etiikka eli kysymykset siitä, kuinka rakastavaisten välinen suhde voisi toteutua ilman että kumpikaan pyrkisi haltuunottamaan toista. Objektivoivan analyysin sijaan tutkimusmenetelmänäni on rakkaudellinen vuoropuhelu niin valitsemieni kaunokirjallisten teosten kuin Irigarayn filosofiankin kanssa. Seuraan tässä Irigarayn ja toisen ranskalaisen ajattelijan Hélène Cixous'n työskentelytapoja - heidän mukaansa pysähtyvä ja kuulosteleva asenne on pyrkivää ja tarttuvaa otetta hedelmällisempi niin inhimillistä toista kuin kirjallistakin toista lähestyttäessä, sillä sen avulla toinen voi säilyttää liikkuvuutensa, arvaamattomuutensa ja vapautensa. Työni tulokset ovat johtopäätösten sijaan avauksia. Jatkan tutkimuksessani Irigarayn työtä ulottamalla hänen samuuden järjestyksen kritiikkinsä ja sukupuolieron etiikan hahmottelunsa kirjallisuudentutkimuksen alueelle. Irigarayta seuraten ajattelen uudelleen naisen ja miehen, henkisen ja ruumiillisen, aistimellisen ja transsendentaalisen välisiä suhteita. Tehtävänämme ei ole muodostaa rakkauden teoriaa tai rakastavaisten välisen etiikan ohjelmaa, vaan tutkia mitä etiikka merkitsee ja voisi merkitä rakkauden alueella.

New mobilities for accessible cities: Toward scenarios for seamless journeys

While cities increasingly attest to plans to make their resources accessible for people with disabilities, the realities of achieving the travel considered integral to urban life continue to be frustrating and prohibitive for this group. Accessing the basic opportunities of contemporary urban life now presupposes the supports and resources afforded by new mobilities, combining virtual and actual travel and communication in negotiating our work, leisure, connections with families and culture. For the researchers applying the new mobilities paradigm, this requires a focus which is suited to capturing movement and its spatial and temporal coordinates and should also turn to illuminate the darker side of these relationships: coerced immobility experienced by people with disabilities. This chapter discusses an approach to research and the development of design scenarios – concepts emerging from research that may inform design - that take seriously the role of movement, time and space in the achievement of valued connections by individuals with disabilities with particular reference to the journey to work. In particular we apply, in a case study, concepts of time and space that are relevant to the in situ experience of getting to work; raising questions regarding the way getting ready and travelling are experienced in the context of risk and contingency and the actual and potential role of the technical, material and social environment. We then respond to the analysis of this case with a discussion about the way emergent scenarios can imagine “possible or preferable futures” for the mobile citizenship of people with disabilities.

Institute for Community College Development Addresses Leadership Crisis

[Excerpt] It is projected that between 2001 and 2007, 47 percent of community college presidents will have left their positions. At a time when challenges are growing more complex, the senior administrators who typically moved into presidencies are also "aging out," leaving fewer qualified individuals in the pipeline. The Institute for Community College Development (ICCD), a partnership between the State University of New York (SUNY) and Cornell, was founded by a group of community college presidents to respond to this leadership crisis. ICCD has been part of ILR since 2001.

Guaiac versus immunochemical tests: Faecal occult blood test screening for colorectal cancer in a rural community

Objective: To describe patient participation and clinical performance in a colorectal cancer (CRC) screening program utilising faecal occult blood test (FOBT). Methods: A community-based intervention was conducted in a small, rural community in north Queensland, 2000/01. One of two FOBT kits – guaiac (Hemoccult-ll) or immunochemical (Inform) – was assigned by general practice and mailed to participants (3,358 patients aged 50–74 years listed with the local practices). Results: Overall participation in FOBT screening was 36.3%. Participation was higher with the immunochemical kit than the guaiac kit (OR=1.9, 95% Cl 1.6-2.2). Women were more likely to comply with testing than men (OR=1.4, 95% Cl 1.2-1.7), and people in their 60s were less likely to participate than those 70–74 years (OR=0.8, 95% Cl 0.6-0.9). The positivity rate was higher for the immunochemical (9.5%) than the guaiac (3.9%) test (χ2=9.2, p=0.002), with positive predictive values for cancer or adenoma of advanced pathology of 37.8% (95% Cl 28.1–48.6) for !nform and 40.0% (95% Cl 16.8–68.7) for Hemoccult-ll. Colonoscopy follow-up was 94.8% with a medical complication rate of 2–3%. Conclusions: An immunochemical FOBT enhanced participation. Higher positivity rates for this kit did not translate into higher false-positive rates, and both test types resulted in a high yield of neoplasia. Implications: In addition to type of FOBT, the ultimate success of a population-based screening program for CRC using FOBT will depend on appropriate education of health professionals and the public as well as significant investment in medical infrastructure for colonoscopy follow-up.

Undead yakuza: The Japanese zombie movie, cultural resonance and generic conventions

The zombie has long been regarded as a “fundamentally American creation” (Bishop 2010) and a western monster representing the fears and anxieties of Western society. Since the renaissance of the zombie movie in the early 2000s, a subsequent surge in international production has seen the release of movies from Norway, Cuba, Pakistan and Thailand to name a few. Although Japanese zombie movies have been far more visible for Western cult audiences than in mainstream markets, Japanese cinema has emerged as one of the more prolific producers of zombie films outside of Anglophone or Western European countries in recent years. Films such as Helldriver (2010), Zombie TV (2013), Versus (2000), Tokyo Zombie (2005), Happiness of the Katakuris (2001) and anime television series High School of the Dead (2010) have generated varying degrees of popularity and critical attention internationally. At first glance Japanese zombie films, with musical zombie interludes, undead yakuza henchmen and revenge-seeking yūrei zombies, appear fundamentally different to their Western counterparts. Yet, on closer examination, the Japanese zombie movie could be regarded as a hybrid and intertextual generic form drawing on syntactic conventions at the core of a universal zombie sub-genre established by Western filmmaking traditions, while also distilling culturally specific tropes unique to various Japanese horror cinema sub-genres. Most importantly, the Japanese zombie film extracts, emphasises and revises particular conventions and motifs common within Western zombie films that are particularly relevant to Japanese audiences. This chapter investigates the cultural resonance of key generic motifs identifiable in the Japanese zombie film. It establishes a production context and the influence of Japanese horror cinema on style and thematic concerns. It then examines the function of prominent narrative conventions, namely: the source, outbreak and spread of infection; mutation and the representation of the monster; and the inclusion of supernatural and religious motifs.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

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.

Improving added value and small medium enterprises capacity in the utilisation of plantation timber for furniture production in Jepara region

Improving added value and Small Medium Enterprises capacity in the utilisation of plantation timber for furniture production in Jepara region of Indonesia: improving recovery, design, manufacturing, R&D and training capacities.

FTO genotype is associated with phenotypic variability of body mass index

There is evidence across several species for genetic control of phenotypic variation of complex traits1, 2, 3, 4, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ~170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)5, 6, 7, is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ~0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation9, 10. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.

ACIAR Improving Postrainy Sorghum Varieties Grain and Fodder in India

Sorghum grown in India in the post-rainy season (Rabi) relies on residual soil moisture, and the crop is commonly exposed to terminal drought stress. But there is a ready market for its high-quality grain and stover (used as fodder on dairy farms). Steps to improve productivity while maintaining quality offer an attractive opportunity for sorghum farmers to improve their incomes. Genetically improving the efficiency of using stored soil moisture is a prime target to maximise grain/stover production and quality of Rabi sorghum. This project aims to achieve this through the application of DNA sequences known as quantitative trait loci (QTLs). The project scientists will introduce marker-assisted introgression of stay-green QTLs into sorghum lines, enhancing both the quality and the quantity of grain/stover of postrainy sorghum. They will also use modelling to identify the key physiological traits involved in a higher, more stable yield across water-limited environments of India and Australia, and the key stay-green QTLs contributing to these traits. The publicly available QTL isolines lines developed in this project will be the basis of new varieties to be bred in a subsequent phase.

DAQ00085 Identifying Candidate Genes for Stay-Green in Sorghum

Identifying candidate genes for drought adaptation in sorghum.

Addressing lodging in sorghum

Developing sorghum varieties with increased lodging resistance has repeatedly been identified as a high priority issue by the Research Advisory Committees for the Northern Region Grains Industry. It is estimated that every third year about 20 to 30% of the area planted to sorghum is affected by lodging. Calculated on the gross value of grain sorghum produced, estimated by DEEDI forecasts of $265m for 2008-09 that could equate to a loss of gross value of production of around $50m in such a year. We intend to submit an eConcept to GRDC for funding for a detailed physiological study addressing this problem.

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10−9 to P = 1.8 × 10−40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10−3 to P = 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.