| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Chapin, III F.S., et al.
(författare)
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Resilience-based stewardship : Strategies for navigating sustainable pathways in a changing world.
- 2009
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Ingår i: Principles of ecosystem stewardship. - New York : Springer Verlag. - 9780387730332 ; , s. 319-337
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Bokkapitel (populärvet., debatt m.m.)abstract
- Accelerated global changes in climate, environment, and social–ecological systems demand a transformation in human perceptions of our place in nature and patterns of resource use. The biology and culture of Homo sapiens evolved for about 95% of our species’ history in hunting-and-gathering societies before the emergence of settled agriculture. We have lived in complex societies for about 3%, and in industrial societies using fossil fuels for about 0.1% of our history. The pace of cultural evolution, including governance arrangements and resource-use patterns, appears insufficient to adjust to the rate and magnitude of technological innovations, human population increases, and environmental impacts that have occurred. Many of these changes are accelerating, causing unsustainable exploitation of ecosystems, including many boreal and tropical forests, drylands, and marine fisheries. The net effect has been serious degradation of the planet’s life-support system on which societal development ultimately depends (see Chapters 2 and 14.
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| 3. |
- Huth, Cornelia, et al.
(författare)
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IL6 gene promoter polymorphisms and type 2 diabetes - Joint analysis of individual participants' data from 21 studies
- 2006
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Ingår i: DIABETES. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:10, s. 2915-2921
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Tidskriftsartikel (refereegranskat)abstract
- Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, −174G>C (rs1800795) and −573G>C (rs1800796), have been investigated for association with type 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 −174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found between IL6 −573G>C and type 2 diabetes. The observed association of the IL6 −174 C-allele with a reduced risk of type 2 diabetes provides further evidence for the hypothesis that immune mediators are causally related to type 2 diabetes; however, because the association is borderline significant, additional data are still needed to confirm this finding.
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| 4. |
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| 5. |
- Abel-Ollo, K., et al.
(författare)
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Knowledge of HIV serostatus and risk behaviour among injecting drug users in Estonia
- 2009
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Ingår i: AIDS Care. - : Informa UK Limited. - 0954-0121 .- 1360-0451. ; 21:7, s. 851-857
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Tidskriftsartikel (refereegranskat)abstract
- We used the findings from two, cross-sectional studies of HIV serostatus and risk behaviours to assess the effects of knowledge of HIV serostatus and risk behaviours (relating to sex and injection drug use) among injecting drug users (IDUs). Respondent-driven sampling was used simultaneously at two sites in Estonia (the capital Tallinn, and the second-largest city of Ida-Virumaa County, Kohtla-Järve). The research tool was an interviewer-administered survey. Biological samples were collected for HIV testing. Participants were categorised into three groups based on HIV testing results and self-report on HIV serostatus: HIV-negative (n=133); HIV-positive unaware of their serostatus (n=75); and HIV-positive aware of their serostatus (n=168). In total, 65% of the participants tested positive for HIV. Of those 69% were aware of their positive serostatus. HIV-positive IDUs aware of their serostatus exhibited more risk behaviours than their HIV-positive counterparts unaware of their serostatus or HIV-negative IDUs. Effective prevention of HIV among IDUs should therefore, include programmes to reduce high-risk sexual and drug use behaviours at the public health scale and enhanced prevention efforts focusing on HIV-infected individuals.
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| 6. |
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| 7. |
- Margulies, Elliott H, et al.
(författare)
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Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 760-774
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Tidskriftsartikel (refereegranskat)abstract
- A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.
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| 8. |
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| 9. |
- Talu, A., et al.
(författare)
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HIV infection and risk behaviour of primary fentanyl and amphetamine injectors in Tallinn, Estonia : Implications for intervention
- 2009
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Ingår i: International journal on drug policy. - : Elsevier BV. - 0955-3959 .- 1873-4758. ; 21:1, s. 56-63
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Tidskriftsartikel (refereegranskat)abstract
- Background Following a heroin shortage, fentanyl and 3-methylfentanyl, known as “China White” and “White Persian”, have become the most widely used drugs, along with amphetamine, among injecting drug users (IDUs) in Tallinn, Estonia. Methods In order to assess the relationships between the injection of fentanyl and amphetamine, and levels of HIV prevalence and risk behaviour, 350 current IDUs were recruited using respondent-driven sampling for an interviewer-administered unlinked cross-sectional survey and HIV testing. IDUs were categorised into groups based on self-report of the main drug used within the last 28 days. Results 77% (256/331) of participants reported fentanyl and 23% (75/331) amphetamine as their main drug of injection. HIV prevalence was 27% (95% confidence interval [CI]: 18.45–35.51) and 62% (95% CI: 56.97–67.03) among amphetamine and fentanyl injectors, respectively. After adjustment, fentanyl injectors had three times the odds of being HIV positive (adjusted odds ratio [AOR] = 2.89; 95% CI: 1.55–5.39). They also had higher odds for injecting in the street with a previously used needle/syringe (AOR = 2.39; 95% CI: 1.14–5.04) and sharing a needle/syringe with somebody known to have HIV (AOR = 3.00, 95% CI: 1.33–6.79). Fentanyl injectors also had higher odds for lifetime overdose (AOR = 3.02, 95% CI: 1.65–5.54). Conclusion The injection of fentanyl is associated with elevated injecting risk behaviour derived from injection practice and situational risk factors, and needs urgently targeted interventions.
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