941 resultados para Lea
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Background The Pacific Oceania region was one of the last regions of the world to be settled via human migration. Here we outline a settlement of this region that has given rise to a uniquely admixed population. The current Norfolk Island population has arisen from a small number of founders with mixed Caucasian and Polynesian ancestry, descendants of a famous historical event. The Mutiny on the Bounty has been told in history books, songs and the big screen, but recently this story can be portrayed through comprehensive molecular genetics. Written history details betrayal and murder leading to the founding of Pitcairn Island by European mutineers and the Polynesian women who left Tahiti with them. Investigation of detailed genealogical records supports historical accounts. Findings Using genetics, we show distinct maternal Polynesian mitochondrial lineages in the present day population, as well as a European centric Y-chromosome phylogeny. These results comprehensively characterise the unique gender-biased admixture of this genetic isolate and further support the historical records relating to Norfolk Island. Conclusions Our results significantly refine previous population genetic studies investigating Polynesian versus Caucasian diversity in the Norfolk Island population and add information that is beneficial to future disease and gene mapping studies.
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Background Breast cancer (BC) is primarily considered a genetic disorder with a complex interplay of factors including age, gender, ethnicity, family history, personal history and lifestyle with associated hormonal and non-hormonal risk factors. The SNP rs2910164 in miR146a (a G to C polymorphism) was previously associated with increased risk of BC in cases with at least a single copy of the C allele in breast cancer, though results in other cancers and populations have shown significant variation. Methods In this study, we examined this SNP in an Australian sporadic breast cancer population of 160 cases and matched controls, with a replicate population of 403 breast cancer cases using High Resolution Melting. Results Our analysis indicated that the rs2910164 polymorphism is associated with breast cancer risk in both primary and replicate populations (p = 0.03 and 0.0013, respectively). In contrast to the results of familial breast cancer studies, however, we found that the presence of the G allele of rs2910164 is associated with increased cancer risk, with an OR of 1.77 (95% CI 1.402.23). Conclusions The microRNA miR146a has a potential role in the development of breast cancer and the effects of its SNPs require further inquiry to determine the nature of their influence on breast tissue and cancer.
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The methylenetetrahydrofolate reductase (MTHFR) gene codes for the MTHFR enzyme which plays a key role in the pathway of folate and methionine metabolism. Polymorphisms of genes in this pathway affect its regulation and have been linked to lymphoma. In this study we examined whether we could detect an association between two common non-synonomous MTHFR polymorphisms, 677C>T (rs1801133) and 1298A>C (rs1801131), and susceptibility to non-Hodgkin lymphoma (NHL) in an Australian case-control cohort. We found no significant differences between genotype or allele frequencies for either polymorphisms between lymphoma cases and controls. We also explored whether epigenetic modification of MTHFR, specifically DNA methylation of a CpG island in the MTHFR promoter region, is associated with NHL using blood samples from patients. No difference in methylation levels was detected between the case and control samples suggesting that although hypermethylation of MTHFR has been reported in tumour tissues, particularly in the diffuse large B-cell lymphoma subtype of NHL, methylation of this MTHFR promoter CpG island is not a suitable epigenetic biomarker for NHL diagnosis or prognosis in peripheral blood samples. Further studies into epigenetic variants could focus on genes that are robustly associated with NHL susceptibility.
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Background Located in the Pacific Ocean between Australia and New Zealand, the unique population isolate of Norfolk Island has been shown to exhibit increased prevalence of metabolic disorders (type-2 diabetes, cardiovascular disease) compared to mainland Australia. We investigated this well-established genetic isolate, utilising its unique genomic structure to increase the ability to detect related genetic markers. A pedigree-based genome-wide association study of 16 routinely collected blood-based clinical traits in 382 Norfolk Island individuals was performed. Results A striking association peak was located at chromosome 2q37.1 for both total bilirubin and direct bilirubin, with 29 SNPs reaching statistical significance (P<1.84107). Strong linkage disequilibrium was observed across a 200 kb region spanning the UDP-glucuronosyltransferase family, including UGT1A1, an enzyme known to metabolise bilirubin. Given the epidemiological literature suggesting negative association between CVD-risk and serum bilirubin we further explored potential associations using stepwise multivariate regression, revealing significant association between direct bilirubin concentration and type-2 diabetes risk. In the Norfolk Island cohort increased direct bilirubin was associated with a 28 % reduction in type-2 diabetes risk (OR: 0.72, 95 % CI: 0.57-0.91, P=0.005). When adjusted for genotypic effects the overall model was validated, with the adjusted model predicting a 30 % reduction in type-2 diabetes risk with increasing direct bilirubin concentrations (OR: 0.70, 95 % CI: 0.53-0.89, P=0.0001). Conclusions In summary, a pedigree-based GWAS of blood-based clinical traits in the Norfolk Island population has identified variants within the UDPGT family directly associated with serum bilirubin levels, which is in turn implicated with reduced risk of developing type-2 diabetes within this population.
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Background Expenditure on dental and oral health services in Australia is $3.4 billion AUD annually. This is the sixth highest health cost and accounts for 7 % of total national health expenditure. Approximately 49 % of Australian children aged 6 years have caries experience in their deciduous teeth and this is rising. The aetiology of dental caries involves a complex interplay of individual, behavioural, social, economic, political and environmental conditions, and there is increasing interest in genetic predisposition and epigenetic modification. Methods The Oral Health Sub-study; a cross sectional study of a birth cohort began in November 2012 by examining mothers and their children who were six years old by the time of initiation of the study, which is ongoing. Data from detailed questionnaires of families from birth onwards and data on mothers knowledge, attitudes and practices towards oral health collected at the time of clinical examination are used. Subjects height, weight and mid-waist circumference are taken and Body Mass Index (BMI) computed, using an electronic Bio-Impedance balance. Dental caries experience is scored using the International Caries Detection and Assessment System (ICDAS). Saliva is collected for physiological measures. Salivary Deoxyribose Nucleic Acid (DNA) is extracted for genetic studies including epigenetics using the SeqCap Epi Enrichment Kit. Targets of interest are being confirmed by pyrosequencing to identify potential epigenetic markers of caries risk. Discussion This study will examine a wide range of potential determinants for childhood dental caries and evaluate inter-relationships amongst them. The findings will provide an evidence base to plan and implement improved preventive strategies.
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Background Multiple sclerosis (MS) is thought to be a T cell-mediated autoimmune disorder. MS pathogenesis is likely due to a genetic predisposition triggered by a variety of environmental factors. Epigenetics, particularly DNA methylation, provide a logical interface for environmental factors to influence the genome. In this study we aim to identify DNA methylation changes associated with MS in CD8+ T cells in 30 relapsing remitting MS patients and 28 healthy blood donors using Illumina 450K methylation arrays. Findings Seventy-nine differentially methylated CpGs were associated with MS. The methylation profile of CD8+ T cells was distinctive from our previously published data on CD4+ T cells in the same cohort. Most notably, there was no major CpG effect at the MS risk gene HLA-DRB1 locus in the CD8+ T cells. Conclusion CD8+ T cells and CD4+ T cells have distinct DNA methylation profiles. This casecontrol study highlights the importance of distinctive cell subtypes when investigating epigenetic changes in MS and other complex diseases.
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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 10300, 2.1 106, 2.5 1010 and 1.8 1010, 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.
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Multiple sclerosis (MS) is a chronic relapsing-remitting inflammatory disease of the central nervous system characterized by oligodendrocyte damage, demyelination and neuronal death. Genetic association studies have shown a 2-fold or greater prevalence of the HLA-DRB1*1501 allele in the MS population compared with normal Caucasians. In discovery cohorts of Australasian patients with MS (total 2941 patients and 3008 controls), we examined the associations of 12 functional polymorphisms of P2X7, a microglial/macrophage receptor with proinflammatory effects when activated by extracellular adenosine triphosphate (ATP). In discovery cohorts, rs28360457, coding for Arg307Gln was associated with MS and combined analysis showed a 2-fold lower minor allele frequency compared with controls (1.11% for MS and 2.15% for controls, P = 0.0000071). Replication analysis of four independent European MS casecontrol cohorts (total 2140 cases and 2634 controls) confirmed this association [odds ratio (OR) = 0.69, P = 0.026]. A meta-analysis of all Australasian and European cohorts indicated that Arg307Gln confers a 1.8-fold protective effect on MS risk (OR = 0.57, P = 0.0000024). Fresh human monocytes heterozygous for Arg307Gln have >85% loss of pore function of the P2X7 receptor measured by ATP-induced ethidium uptake. Analysis shows Arg307Gln always occurred with 270His suggesting a single 307Gln270His haplotype that confers dominant negative effects on P2X7 function and protection against MS. Modeling based on the homologous zP2X4 receptor showed Arg307 is located in a region rich in basic residues located only 12 from the ligand binding site. Our data show the protective effect against MS of a rare genetic variant of P2RX7 with heterozygotes showing near absent proinflammatory pore function.
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The rise of Special education numbers in Finland has caused a situation where Finland s ten largest LEA s so called kymppikunnat (ten communes) have expressed their growing concern of organizing the special education in the current institutional settings. The LEA s started the conversation of redefining special education system in 2004. Their aim was to target the governments attention to the problematics of special education. By the request of the Ministry of Education the LEA s prepared a final report concerning the central questions in the Finnish special education system. On the basis of the LEA s survey it became even clearer that the legislation, funding system and curriculum are tightly linked together. The following LEA s took part into the writing process Espoo, Helsinki, Jyvskyl, Kuopio, Lahti, Lappeenranta, Tampere, Turku and Vantaa. The report was hand over to the Ministry of Education at 18.8.2006. After the delivery the Ministry organized special education development group meetings 17 times in the year 2007. The result of the LEA s report and the development meetings was a new Special Education Strategy 2007. I am observing the dialogue between administrational levels in governmental institutions change process. The research is a content analysis where I compare the Erityist tukea tarvitsevan oppilaan opetuksen jrjestmisen uudistaminen osana yhtenist perusopetusta- kohti laatua ja joustavuutta (The renewal of the organization of teaching for student with special educational needs as part of unified education for all - towards quality and flexibility) document to Erityisopetuksen strategia (Special education strategy) document. My aim was to find out how much of their own interests have the LEA s been able to integrate into the official governmental documentation. The data has been organized and analyzed quantitatively with Macros created as additional parts in Microsoft Excel software. The document material has also been arranged manually on sentence based categorization into an Excel matrix. The results have been theoretically viewed from the special education reform dialogue perspective, and from the angle of the change process of a bureaucratic institution. My target has been to provide a new viewpoint to the change of special education system as a bureaucratic institution. The education system has traditionally been understood as a machine bureaucracy. By the review provided in my pro gradu analysis it seems however that the administrational system in special education is more of a postmodern network bureaucracy than machine bureaucracy. The system appears to be constructed by overlapping, crossing and complex networks where things are been decided. These kinds of networks are called "governance networks . It seems that the governmental administrational - and politic levels, the third sector actors and other society s operators are mixed in decision making.
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Tutkimuksen tavoitteena on selvitt, mik saa pitkn tyuran tehneet sairaanhoitajat innostumaan tystn. Taustalla on yhteiskunnallinen tilanne, jossa tyelmn vetovoimaisuuden lisminen ja ikntyvien tyntekijiden tyss jaksaminen ovat keskeisi poliittisia tavoitteita. Aihetta lhestytn positiivisesta psykologiasta lhtisin olevan tyn imun ksitteen avulla. Se on mritelty pysyvksi, mynteiseksi, tunne- ja motivaatiotyttymyksen tilaksi, jota luonnehtivat tarmokkuus, omistautuminen ja uppoutuminen tyhn (Hakanen 2009a, 9). Tutkimuksessa kysytn, voidaanko tyn imua ymmrt mys sosiologisesta nkkulmasta. Oletuksena on, ett ksitteen taustalla on muutakin kuin psykologisesta perinteest ksin jsentyv vaihtelua. Empiirisen aineiston muodostavan 11 sairaanhoitajan koko tyuraa ja nykyist tyt koskevat tiettyihin teemoihin ankkuroidut syvhaastattelut. Otosta poimittaessa on etsitty sellaisia haastateltavia, jotka kokevat kantavansa tyn imua. Aineiston analyysitapana on kytetty matriisin avulla sovellettua kvalitatiivista sisllnanalyysi. Tyn imua hahmotetaan analyysiss henkilhistoriallisten haastatteluiden menneen, nykyisen ja tulevan kautta. Pyrkimyksen on etsi tarinoita mahdollisesti yhdistv kulttuurista muotoa ja ymmrt, mihin se perustuu. Analyysin nojalla vastuurationaalisuuden ksite (esim. Korvajrvi 1986) nyttisi jsentvn osan haastateltavien suhteesta tyhns. Avain tyn imun lytymiseen niss tarinoissa on kuitenkin se, kuinka haastateltavilla on ollut henkilkohtainen halu menn eteenpin ja kyky ratkaista ongelmia tyuransa aikana ja nykyisess tyssn. Tm havainto tulkitaan Max Weberin (1922, 1980) ksitteiden arvorationaalisen ja pmrrationaalisen toiminnan vliseen suhteen avulla. Tulokseksi syntyy oletus siit, ett analyysin kohteena olevissa tarinoissa on kyse yhteisest kulttuurisesta tarinasta siit, millainen on hyv ihminen, miten hyv ihminen toteuttaa itsen tyss ja miten hn tekee tytn: tarmokkaasti, omistautuen ja uppoutuen. Henkilkohtainen halu menn eteenpin ja kyky ratkaista ongelmia nojaa sairaanhoitajien erityiseen eetokseen, kutsumustyhn ja hoivan moraaliin tavalla, joka on rakenteellisesti yhtlinen protestanttisuutta leimaavan yksilllisen jumalasuhteen kanssa. Lisksi analyysin perusteella esitetn, ett tyn imun edellytys on arvorationaalisen eetoksen lisksi oikeanlainen, riittvt tyn voimavarat sisltv ymprist, jossa hoitotyn keskeiset palkinnot on mahdollista saavuttaa. Tllin palkkatyn sislt kohtaa kulttuuriset lhtkohdat, ja tulos nkyy tyn imuna. Keskeisimmt taustoittavat lhteet ovat Henriksson, Lea & Wrede, Sirpa (toim.) (2004a). Hyvinvointityn ammatit ja Hakanen, Jari (2009a). Tyn imun arviointimenetelm (Utrecht Work Engagement Scale). Sosiologisen tulkinnan kannalta trkein teoreettinen lhde on Weber, Max (1980): Protestanttinen etiikka ja kapitalismin henki.
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Tieteellinen tiivistelm Common scab is one of the most important soil-borne diseases of potato (Solanum tuberosum L.) in many potato production areas. It is caused by a number of Streptomyces species, in Finland the causal agents are Streptomyces scabies (Thaxter) Lambert & Loria and S. turgidiscabies Takeuchi. The scab-causing Streptomyces spp. are well-adapted, successful plant pathogens that survive in soil also as saprophytes. Control of these pathogens has proved to be difficult. Most of the methods used to manage potato common scab are aimed at controlling S. scabies, the most common of the scab-causing pathogens. The studies in this thesis investigated S. scabies and S. turgidiscabies as causal organisms of common scab and explored new approaches for control of common scab that would be effective against both species. S. scabies and S. turgidiscabies are known to co-occur in the same fields and in the same tuber lesions in Finland. The present study showed that both these pathogens cause similar symptoms on potato tubers, and the types of symptoms varied depending on cultivar rather than the pathogen species. Pathogenic strains of S. turgidiscabies were antagonistic to S. scabies in vitro indicating that these two species may be competing for the same ecological niche. In addition, strains of S. turgidiscabies were highly virulent in potato and they tolerated lower pH than those of S. scabies. Taken together these results suggest that S. turgidiscabies has become a major problem in potato production in Finland. The bacterial phytotoxins, thaxtomins, are produced by the scab-causing Streptomyces spp. and are essential for the induction of scab symptoms. In this study, thaxtomins were produced in vitro and four thaxtomin compounds isolated and characterized. All four thaxtomins induced similar symptoms of reduced root and shoot growth, root swelling or necrosis on micro-propagated potato seedlings. The main phytotoxin, thaxtomin A, was used as a selective agent in a bioassay in vitro to screen F1 potato progeny from a single cross. Tolerance to thaxtomin A in vitro and scab resistance in the field were correlated indicating that the in vitro bioassay could be used in the early stages of a resistance breeding program to discard scab-susceptible genotypes and elevate the overall levels of common scab resistance in potato breeding populations. The potential for biological control of S. scabies and S. turgidiscabies using a non-pathogenic Streptomyces strain (346) isolated from a scab lesion and S. griseoviridis strain (K61) from a commercially available biocontrol product was studied. Both strains showed antagonistic activity against S. scabies and S. turgidiscabies in vitro and suppressed the development of common scab disease caused by S. turgidiscabies in the glasshouse. Furthermore, strain 346 reduced the incidence of S. turgidiscabies in scab lesions on potato tubers in the field. These results demonstrated for the first time the potential for biological control of S. turgidiscabies in the glasshouse and under field conditions and may be applied to enhance control of common scab in the future.
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"The increasing pressure for enterprises to join into agile business networks is changing the requirements on the enterprise computing systems. The supporting infrastructure is increasingly required to provide common facilities and societal infrastructure services to support the lifecycle of loosely-coupled, eContract-governed business networks. The required facilities include selection of those autonomously administered business services that the enterprises are prepared to provide and use, contract negotiations, and furthermore, monitoring of the contracted behaviour with potential for breach management. The essential change is in the requirement of a clear mapping between business-level concepts and the automation support for them. Our work has focused on developing B2B middleware to address the above challenges; however, the architecture is not feasible without management facilities for trust-aware decisions for entering business networks and interacting within them. This paper discusses how trust-based decisions are supported and positioned in the B2B middleware."
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Inter-enterprise collaboration has become essential for the success of enterprises. As competition increasingly takes place between supply chains and networks of enterprises, there is a strategic business need to participate in multiple collaborations simultaneously. Collaborations based on an open market of autonomous actors set special requirements for computing facilities supporting the setup and management of these business networks of enterprises. Currently, the safeguards against privacy threats in collaborations crossing organizational borders are both insufficient and incompatible to the open market. A broader understanding is needed of the architecture of defense structures, and privacy threats must be detected not only on the level of a private person or enterprise, but on the community and ecosystem levels as well. Control measures must be automated wherever possible in order to keep the cost and effort of collaboration management reasonable. This article contributes to the understanding of the modern inter-enterprise collaboration environment and privacy threats in it, and presents the automated control measures required to ensure that actors in inter-enterprise collaborations behave correctly to preserve privacy.
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Tutkimuksen tavoitteena on selvitt, mik saa pitkn tyuran tehneet sairaanhoitajat innostumaan tystn. Taustalla on yhteiskunnallinen tilanne, jossa tyelmn vetovoimaisuuden lisminen ja ikntyvien tyntekijiden tyss jaksaminen ovat keskeisi poliittisia tavoitteita. Aihetta lhestytn positiivisesta psykologiasta lhtisin olevan tyn imun ksitteen avulla. Se on mritelty pysyvksi, mynteiseksi, tunne- ja motivaatiotyttymyksen tilaksi, jota luonnehtivat tarmokkuus, omistautuminen ja uppoutuminen tyhn (Hakanen 2009a, 9). Tutkimuksessa kysytn, voidaanko tyn imua ymmrt mys sosiologisesta nkkulmasta. Oletuksena on, ett ksitteen taustalla on muutakin kuin psykologisesta perinteest ksin jsentyv vaihtelua. Empiirisen aineiston muodostavan 11 sairaanhoitajan koko tyuraa ja nykyist tyt koskevat tiettyihin teemoihin ankkuroidut syvhaastattelut. Otosta poimittaessa on etsitty sellaisia haastateltavia, jotka kokevat kantavansa tyn imua. Aineiston analyysitapana on kytetty matriisin avulla sovellettua kvalitatiivista sisllnanalyysi. Tyn imua hahmotetaan analyysiss henkilhistoriallisten haastatteluiden menneen, nykyisen ja tulevan kautta. Pyrkimyksen on etsi tarinoita mahdollisesti yhdistv kulttuurista muotoa ja ymmrt, mihin se perustuu. Analyysin nojalla vastuurationaalisuuden ksite (esim. Korvajrvi 1986) nyttisi jsentvn osan haastateltavien suhteesta tyhns. Avain tyn imun lytymiseen niss tarinoissa on kuitenkin se, kuinka haastateltavilla on ollut henkilkohtainen halu menn eteenpin ja kyky ratkaista ongelmia tyuransa aikana ja nykyisess tyssn. Tm havainto tulkitaan Max Weberin (1922; 1980) ksitteiden arvorationaalisen ja pmrrationaalisen toiminnan vliseen suhteen avulla. Tulokseksi syntyy oletus siit, ett analyysin kohteena olevissa tarinoissa on kyse yhteisest kulttuurisesta tarinasta siit, millainen on hyv ihminen, miten hyv ihminen toteuttaa itsen tyss ja miten hn tekee tytn: tarmokkaasti, omistautuen ja uppoutuen. Henkilkohtainen halu menn eteenpin ja kyky ratkaista ongelmia nojaa sairaanhoitajien erityiseen eetokseen, kutsumustyhn ja hoivan moraaliin tavalla, joka on rakenteellisesti yhtlinen protestanttisuutta leimaavan yksilllisen jumalasuhteen kanssa. Lisksi analyysin perusteella esitetn, ett tyn imun edellytys on arvorationaalisen eetoksen lisksi oikeanlainen, riittvt tyn voimavarat sisltv ymprist, jossa hoitotyn keskeiset palkinnot on mahdollista saavuttaa. Tllin palkkatyn sislt kohtaa kulttuuriset lhtkohdat, ja tulos nkyy tyn imuna. Keskeisimmt taustoittavat lhteet ovat Henriksson, Lea & Wrede, Sirpa (toim.) (2004a). Hyvinvointityn ammatit ja Hakanen, Jari (2009a). Tyn imun arviointimenetelm (Utrecht Work Engagement Scale). Sosiologisen tulkinnan kannalta trkein teoreettinen lhde on Weber, Max (1980): Protestanttinen etiikka ja kapitalismin henki.