Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10−8) loci, some including known iron-related genes (​HFE, ​SLC40A1, ​TF, ​TFR2, ​TFRC, ​TMPRSS6) and others novel (​ABO, ​ARNTL, ​FADS2, ​NAT2, ​TEX14). SNPs at ​ARNTL, ​TF, and ​TFR2 affect iron markers in ​HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

Case-control study of ADARB1 and ADARB2 gene variants in migraine

Background: Migraine causes crippling attacks of severe head pain along with associated nausea, vomiting, photophobia and/or phonophobia. The aim of this study was to investigate single nucleotide polymorphisms (SNPs) in the adenosine deaminase, RNA-specific, B1 (ADARB1)and adenosine deaminase, RNA specific, B2 (ADARB2) genes in an Australian case-control Caucasian population for association with migraine. Both candidate genes are highly expressed in the central nervous system (CNS) and fit criteria for migraine neuropathology. SNPs in the ADARB2 gene were previously found to be positively associated with migraine in a pedigree-based GWAS using the genetic isolate of Norfolk Island, Australia. The ADARB1 gene was also chosen for investigation due to its important function in editing neurotransmitter receptor transcripts. Methods: Four SNPs in ADARB1 and nine in ADARB2 were selected by inspecting blocks of LD in Haploview for genotyping using either TaqMan or Sequenom assays. These SNPs were genotyped in two-hundred and ninety one patients who satisfied the International Classification of Headache Disorders, ICHD-II 2004 diagnostic criteria for migraine and three-hundred and fourteen controls and PLINK was used for association testing. Results: Chi-square (χ2) analysis found no significant association between any of the SNPs tested in the ADARB1 and ADARB2 genes in this study and the occurrence of migraine. Conclusions: In contrast to findings that SNPs in the ADARB2 gene were positively associated with migraine in the Norfolk Island population, we find no evidence to support the involvement of RNA editing genes in migraine susceptibility in an Australian Caucasian population.

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.

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.

The conservation status of the world’s reptiles

Effective and targeted conservation action requires detailed information about species, their distribution, systematics and ecology as well as the distribution of threat processes which affect them. Knowledge of reptilian diversity remains surprisingly disparate, and innovative means of gaining rapid insight into the status of reptiles are needed in order to highlight urgent conservation cases and inform environmental policy with appropriate biodiversity information in a timely manner. We present the first ever global analysis of extinction risk in reptiles, based on a random representative sample of 1500 species (16% of all currently known species). To our knowledge, our results provide the first analysis of the global conservation status and distribution patterns of reptiles and the threats affecting them, highlighting conservation priorities and knowledge gaps which need to be addressed urgently to ensure the continued survival of the world’s reptiles. Nearly one in five reptilian species are threatened with extinction, with another one in five species classed as Data Deficient. The proportion of threatened reptile species is highest in freshwater environments, tropical regions and on oceanic islands, while data deficiency was highest in tropical areas, such as Central Africa and Southeast Asia, and among fossorial reptiles. Our results emphasise the need for research attention to be focussed on tropical areas which are experiencing the most dramatic rates of habitat loss, on fossorial reptiles for which there is a chronic lack of data, and on certain taxa such as snakes for which extinction risk may currently be underestimated due to lack of population information. Conservation actions specifically need to mitigate the effects of human-induced habitat loss and harvesting, which are the predominant threats to reptiles.

Complete genome sequence and integrated protein localization and interaction map for alfalfa dwarf virus, which combines properties of both cytoplasmic and nuclear plant rhabdoviruses

Summary We have determined the full-length 14,491-nucleotide genome sequence of a new plant rhabdovirus, alfalfa dwarf virus (ADV). Seven open reading frames (ORFs) were identified in the antigenomic orientation of the negative-sense, single-stranded viral RNA, in the order 3′-N-P-P3-M-G-P6-L-5′. The ORFs are separated by conserved intergenic regions and the genome coding region is flanked by complementary 3′ leader and 5′ trailer sequences. Phylogenetic analysis of the nucleoprotein amino acid sequence indicated that this alfalfa-infecting rhabdovirus is related to viruses in the genus Cytorhabdovirus. When transiently expressed as GFP fusions in Nicotiana benthamiana leaves, most ADV proteins accumulated in the cell periphery, but unexpectedly P protein was localized exclusively in the nucleus. ADV P protein was shown to have a homotypic, and heterotypic nuclear interactions with N, P3 and M proteins by bimolecular fluorescence complementation. ADV appears unique in that it combines properties of both cytoplasmic and nuclear plant rhabdoviruses.

The status of entrepreneurship education in Australian universities

Purpose The purpose of this paper is to provide an analytical overview of the current state of entrepreneurship education (EE) in Australia; placing emphasis on programs, curricula and entrepreneurship ecosystems. Design/methodology/approach The authors performed a contextual review of the literature by delineating entrepreneurship education programs, the entrepreneurial ecosystem and EE learning and teaching. The review was enhanced by a systematic collection of data from higher education institutions web sites, depicting the prevailing situation of entrepreneurship programs, courses, subjects and their ecosystems. Findings A number of interesting findings emerged from this study. From a curricular perspective, Australian universities offer 584 subjects related to entrepreneurship. This includes dominance at undergraduate level, representing 24 minors/majors and specializations in entrepreneurship. In total, 135 entrepreneurship ecosystems were identified. Research limitations/implications This paper presents findings from university web sites and as such requires introspection to validate individual university offerings. Practical implications The study provides the status of EE in Australia, and may guide academic and policy decision makers to further develop entrepreneurship initiatives. Originality/value This paper provides the first analytical overview of EE in Australia and paves the way for further evaluation.

Planning neighbourhoods for all ages and abilities: A multi-generational perspective

Taking a more integrated approach to planning our neighbourhoods for the continuum of inhabitants’ ages and abilities makes sense given our current and future population composition. Seldom are the built environment requirements of diverse groups (e.g. children, seniors, and people with disability) synthesised, resulting in often unfriendly and exclusionary neighbourhoods. This often means people experience barriers or restriction on their freedom to move about and interact within their neighbourhood. Applying universal design to neighbourhoods may provide a bridging link. By presenting two cases from South-East Queensland (SEQ), Australia, through the lenses of different ages and abilities - older children with physical disabilities and their families (Stafford 2013, 2014) and seniors (Baldwin et al. 2012), we intend to increase recognition of users' needs and stimulate the translation of knowledge to the practice of planning inclusive neighbourhoods.

Directional dominance on stature and cognition in diverse human populations

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3, 4. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10−300, 2.1 × 10−6, 2.5 × 10−10 and 1.8 × 10−10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months’ less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5, 6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

Revisiting Coptotermes (Isoptera: Rhinotermitidae): a global taxonomic road map for species validity and distribution of an economically important subterranean termite genus

Coptotermes Wasmann (Isoptera: Rhinotermitidae) is one of the most economically important subterranean termite genera and some species are successful invaders. However, despite its important pest status, the taxonomic validity of many named Coptotermes species remains unclear. In this study, we reviewed all named species within the genus and investigated evidence supporting the validity of each named species. Species were systematically scrutinized according to the region of their original description: Southeast Asia, India, China, Africa, the Neotropics, and Australia. We estimate that of the currently 69 named species described by accepted nomenclatural rules, only 21 taxa have solid evidence for validity, 44 names have uncertain status, and the remaining species names should be synonymized or were made unavailable. Species with high degrees of invasiveness may be known under additional junior synonyms due to independent parochial descriptions. Molecular data for a vast majority of species are scarce and significant effort is needed to complete the taxonomic and phylogenetic revision of the genus. Because of the wide distribution of Coptotermes, we advocate for an integrative taxonomic effort to establish the distribution of each putative species, provide specimens and corresponding molecular data, check original descriptions and type specimens (if available), and provide evidence for a more robust phylogenetic position of each species. This study embodies both consensus and contention of those studying Coptotermes and thus pinpoints the current uncertainty of many species. This project is intended to be a roadmap for identifying those Coptotermes species names that need to be more thoroughly investigated, as an incentive to complete a necessary revision process.

Magnetization and magnetoresistive response of LiMn2O4 near the charge ordering transition

We report magnetization and magnetoresistance studies of the geometrically frustrated spinel compound LiMn2O4 near its charge ordering temperature. The effect of a 7 T magnetic field is to very slightly shift the transition in the resistivity to lower temperatures resulting in large negative magnetoresistance with significant hysteresis. This hysteresis is not reflected in the magnetization. These observations are compared with what is found in the colossal magnetoresistance and charge ordering perovskite manganese oxides. The manner in which geometric frustration influences the coupling of charge and spin degrees of freedom is examined.

Synthesis of graphene oxide-intercalated alpha-hydroxides by metathesis and their decomposition to graphene/metal oxide composites

Graphene oxide-intercalated alpha-metal hydroxides were prepared using layers from the delaminated colloidal dispersions of cetyltrimethylammonium-intercalated graphene oxide and dodecylsulfate-intercalated alpha-hydroxide of nickel/cobalt as precursors. The reaction of the two dispersions leads to de-intercalation of the interlayer ions from both the layered solids and the intercalation of the negatively charged graphene oxide sheets between the positively charged layers of the alpha-hydroxide. Thermal decomposition of the intercalated solids yields graphene/nanocrystalline metal oxide composites. Electron microscopy analysis of the composites indicates that the nanoparticles are intercalated between graphene layers. (C) 2010 Elsevier Ltd. All rights reserved.

Symbolinen representaatio: taidetta paperilla : Tanssinotaation käytön tarkastelua musiikkitieteellisten ja tanssitieteellisten teorioiden valossa

Tässä tutkielmassa tutkin tanssin liikemateriaalin kirjoittamista suomalaisessa tanssitaiteessa. Tutkielman tarkoitus on pohtia 1) mikä tanssista taiteenlajina tekee sellaisen, että virallinen notaatio on katsottu tarpeettomaksi, 2) mitä keinoja Suomessa tanssin parissa työskentelevät ovat kehittäneet selviytyäkseen ilman yhteistä notaatiota, sekä 3) miten yhteisen tanssinotaation laajempi käyttö voisi mahdollisesti hyödyttää tanssia. Tutkielman näkökulma on poikkitaiteellinen: vertaan tanssia ja sen käsittämistä taiteena sen sisartaiteeseen, musiikkiin. Tärkeimmät käsitellyt teoreetikot ovat musiikkipsykologi John A. Sloboda, symbolista representaatiota käsitelleet Marc Leman ja Kari Kurkela sekä musiikin ruumiillisuutta tutkinut musiikkitieteilijä Suzanne Cusick. Tanssin tutkimuksen piiristä ammennan teoreettista materiaalia ennen kaikkea Rudolf Labanin ja Valerie Preston-Dunlopin liikkeen analyysista sekä tanssinotaatiota käsitelleiden Claudia Jeschken, Judy Van Zilen, Victoria Wattsin ja Grahm McFeen artikkeleista. Toista tutkimuskysymystä varten keräsin v.2009 kyselyaineiston, jota käytän tukemaan teoreettisia väitteitäni notaation käytöstä. Aineiston keruumetodini oli kyselykaavake, joka lähetettiin jokaiseen Suomen tanssioppilaitokseen ja tanssiteattereihin sekä niille ammattimaisesti toimivien tanssiryhmien tanssijoille ja koreografeille ja itsenäisille toimijoille, joiden yhteystiedot olivat saatavilla Tanssin tiedotuskeskuksen tai Tanssin aluekeskusten kautta. Pienen vastausprosentin vuoksi aineistoa ei ollut mielekästä tutkia kvantitatiivisin menetelmin, vaan vastauksia käsitellään havainnollistavina esimerkkeinä tanssin kentältä. Yleisesti suomalaisen tanssitaiteen kentällä yhteisellä notaatiosysteemillä käsitetään labanotaatiota. Notaatio koetaan varsinaisen tanssin päälle liimattuna asiana, ei taiteenlajin ytimeen kuuluvana tekstinä. Suzan Cusackin ruumiillisuusteoriaa mukaillen huomioin, että musiikki on totuttu käsittämään mielen aktiviteettina, kun taas tanssi on nähty lähes täysin ruumiillisena toimintana. Tätä mielen ja kehon vastakkainasettelua vasten notaatiota on perinteisesti sovellettu musiikkiin, mutta tanssiin ei. Kaikki kyselyyn vastanneet suomalaisen tanssitaiteen ammattilaiset kuitenkin kirjoittivat tanssia muistiin paperille. Kerätty materiaali osoitti siihen suuntaan, että symbolinen representaatio tanssista on tärkeä silloin, kun halutaan kuvata tanssin rakennetta: esimerkiksi teoksen muotoa ja dramaturgiaa. Liikemuistin tukena sen rooli korostuu erityisesti opetustyössä. Niin John A. Sloboda kuin Kari Kurkelakin korostavat symbolisen representaation roolia kommunikaation välineenä; lisäksi sen käyttö voi Graham McFeen mukaan selventää teosidentiteettiä sekä luoda arkistoa paitsi valmiista teoksista, myös koreografisesta prosessista ja esitystavoista. Myös nämä molemmat näkökulmat tulivat esiin aineistossa. Toisin kuin musiikin piirissä, notaatiota ei yleensä opeteta tanssijoille. John A. Slobodaa mukaillen esitän, että minkä tahansa notaation osaaminen saattaa muuttaa tanssin tekijän kognitiivisia prosesseja ja ajattelutapaa tanssista, ja suullisesta kulttuurista kirjoitettuun kulttuuriin siirtyminen pitää sisällään niin etuja kuin riskejäkin. Jos notaation siitä huolimatta halutaan tulevan eläväksi osaksi tanssia ja hyödyntävän sitä taiteenlajina, olisi notaatiokysymykseen otettava uudenlainen pedagoginen lähestymistapa: tanssinotaatiota olisi opetettava alkeistasolta lähtien ja kyseenalaistettava ajatus, jonka mukaan koreologi tai notaattori on erillinen ammatti.