| 1. |
- Birney, Ewan, et al.
(författare)
-
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
-
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.
|
|
| 2. |
- Schmit, Stephanie L, et al.
(författare)
-
Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
|
|
| 3. |
|
|
| 4. |
- Axelsson, Magnus, et al.
(författare)
-
On the origin of black hole spin in high-mass black hole binaries : Cygnus X-1
- 2011
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 412:4, s. 2260-2264
-
Tidskriftsartikel (refereegranskat)abstract
- To date, there have been several detections of high-mass black hole binaries in both the Milky Way and other galaxies. For some of these, the spin parameter of the black hole has been estimated. As many of these systems are quite tight, a suggested origin of the spin is angular momentum imparted by the synchronous rotation of the black hole progenitor with its binary companion. Using Cygnus X-1, the best studied high-mass black hole binary, we investigate this possibility. We find that such an origin of the spin is not likely, and our results point rather to the spin being the result of processes during the collapse.
|
|
| 5. |
- Church, Ross, et al.
(författare)
-
Implications for the origin of short gamma-ray bursts from their observed positions around their host galaxies
- 2011
-
Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 1365-2966 .- 0035-8711. ; 413:3, s. 2004-2014
-
Tidskriftsartikel (refereegranskat)abstract
- We present the observed offsets of short-duration gamma-ray bursts (SGRBs) from their putative host galaxies and compare them with the expected distributions of merging compact object binaries, given the observed properties of the hosts. We find that for all but one burst in our sample the offsets are consistent with this model. For the case of bursts with massive elliptical host galaxies, the circular velocities of the hosts' haloes exceed the natal velocities of almost all our compact object binaries. Hence, the extents of the predicted offset distributions for elliptical galaxies are determined largely by their spatial extents. In contrast, for spiral hosts, the galactic rotation velocities are smaller than typical binary natal velocities and the predicted burst offset distributions are more extended than the galaxies. One SGRB, 060502B, apparently has a large radial offset that is inconsistent with an origin in a merging galactic compact binary. Although it is plausible that the host of GRB 060502B is misidentified, our results show that the large offset is compatible with a scenario where at least a few per cent of SGRBs are created by the merger of compact binaries that form dynamically in globular clusters.
|
|
| 6. |
- Church, Ross, et al.
(författare)
-
Properties of long gamma-ray bursts from massive compact binaries.
- 2013
-
Ingår i: Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Science. - : The Royal Society. - 1364-503X .- 1471-2962. ; 371:1992
-
Tidskriftsartikel (refereegranskat)abstract
- We consider the implications of a model for long-duration gamma-ray bursts in which the progenitor is spun up in a close binary by tidal interactions with a massive black-hole companion. We investigate a sample of such binaries produced by a binary population synthesis, and show that the model predicts several common features in the accretion on to the newly formed black hole. In all cases, the accretion rate declines as approximately t(-5/3) until a break at a time of order 10(4) s. The accretion rate declines steeply thereafter. Subsequently, there is flaring activity, with the flare peaking between 10(4) and 10(5) s, the peak time being correlated with the flare energy. We show that these times are set by the semi-major axis of the binary, and hence the process of tidal spin-up; furthermore, they are consistent with flares seen in the X-ray light curves of some long gamma-ray bursts.
|
|
| 7. |
- Church, Ross, et al.
(författare)
-
The properties of long gamma-ray bursts in massive compact binaries
- 2012
-
Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 1365-2966 .- 0035-8711. ; 425:1, s. 470-476
-
Tidskriftsartikel (refereegranskat)abstract
- We consider a popular model for long-duration gamma-ray bursts, in which the progenitor star, a stripped helium core, is spun up by tidal interactions with a black hole companion in a compact binary. We perform population synthesis calculations to produce a representative sample of such binaries, and model the effect that the companion has on material that falls back on to the newly formed black hole. Taking the results of hydrodynamic models of black hole formation by fallback as our starting point, we show that the companion has two principal effects on the fallback process. First, a break forms in the accretion curve at around 104?s. Secondly, subsequent to the break, we expect to see a flare of total energy around 1050?erg. We show that the break and flare times are set largely by the semimajor axis of the binary at the time of explosion, and that this correlates negatively with the flare energy. Although comparison with observations is non-trivial, we show that our predicted break times are comparable to those found in the X-ray light curves of canonical long-duration gamma-ray bursts. Similarly, the flare properties that we predict are consistent with the late-time flares observed in a subsample of bursts.
|
|
| 8. |
- Fischer, Markus, et al.
(författare)
-
The regional assessment report on biodiversity and ecosystem services for Europe and Central Asia : summary for policymakers
- 2018
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The Regional Assessment Report on Biodiversity and Ecosystem Services for Europe and Central Asia produced by the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) provides a critical analysis of the state of knowledge regarding the importance, status, and trends of biodiversity and nature's contributions to people. The assessment analyses the direct and underlying causes for the observed changes in biodiversity and in nature's contributions to people, and the impact that these changes have on the quality of life of people. The assessment, finally, identifies a mix of governance options, policies and management practices that are currently available to reduce the loss of biodiversity and of nature's contributions to people in that region. The assessment addresses terrestrial, freshwater, and coastal biodiversity and covers current status and trends, going back in time several decades, and future projections, with a focus on the 2020-2050 period.
|
|
| 9. |
|
|
| 10. |
- Gibson, Lucy L, et al.
(författare)
-
NMDA Receptor Antibodies and Neuropsychiatric Symptoms in Parkinson's Disease.
- 2023
-
Ingår i: The Journal of neuropsychiatry and clinical neurosciences. - : American Psychiatric Association Publishing. - 1545-7222 .- 0895-0172. ; 35:3, s. 236-243
-
Tidskriftsartikel (refereegranskat)abstract
- N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoantibody-mediated neurological syndrome with prominent cognitive and neuropsychiatric symptoms. The clinical relevance of NMDAR antibodies outside the context of encephalitis was assessed in this study.Plasma from patients with Parkinson's disease (PD) (N=108) and healthy control subjects (N=89) was screened at baseline for immunoglobulin A (IgA), IgM, and IgG NMDAR antibodies, phosphorylated tau 181 (p-tau181), and the neuroaxonal injury marker neurofilament light (NfL). Clinical assessment of the patients included measures of cognition (Mini-Mental State Examination [MMSE]) and neuropsychiatric symptoms (Hospital Anxiety and Depression Scale; Non-Motor Symptoms Scale for Parkinson's Disease). A subgroup of patients (N=61) was followed annually for up to 6 years.Ten (9%) patients with PD tested positive for NMDAR antibodies (IgA, N=5; IgM, N=6; IgG, N=0), and three (3%) healthy control subjects had IgM NMDAR antibodies; IgA NMDAR antibodies were detected significantly more commonly among patients with PD than healthy control subjects (χ2=4.23, df=1, p=0.04). Age, gender, and disease duration were not associated with NMDAR antibody positivity. Longitudinally, antibody-positive patients had significantly greater decline in annual MMSE scores when the analyses were adjusted for education, age, disease duration, p-tau181, NfL, and follow-up duration (adjusted R2=0.26, p=0.01). Neuropsychiatric symptoms were not associated with antibody status, and no associations were seen between NMDAR antibodies and p-tau181 or NfL levels.NMDAR antibodies were associated with greater cognitive impairment over time in patients with PD, independent of other pathological biomarkers, suggesting a potential contribution of these antibodies to cognitive decline in PD.
|
|
