82 research outputs found
Three-dimensional magnetic resonance reconstruction images before and after surgical therapy of spontaneous canine brain tumors
A Galaxy-scale Fountain of Cold Molecular Gas Pumped by a Black Hole
We present Atacama Large Millimeter/submillimeter Array and Multi-Unit Spectroscopic Explorer observations of the brightest cluster galaxy in Abell 2597, a nearby (z = 0.0821) cool core cluster of galaxies. The data map the kinematics of a three billion solar mass filamentary nebula that spans the innermost 30 kpc of the galaxy's core. Its warm ionized and cold molecular components are both cospatial and comoving, consistent with the hypothesis that the optical nebula traces the warm envelopes of many cold molecular clouds that drift in the velocity field of the hot X-ray atmosphere. The clouds are not in dynamical equilibrium, and instead show evidence for inflow toward the central supermassive black hole, outflow along the jets it launches, and uplift by the buoyant hot bubbles those jets inflate. The entire scenario is therefore consistent with a galaxy-spanning "fountain," wherein cold gas clouds drain into the black hole accretion reservoir, powering jets and bubbles that uplift a cooling plume of low-entropy multiphase gas, which may stimulate additional cooling and accretion as part of a self-regulating feedback loop. All velocities are below the escape speed from the galaxy, and so these clouds should rain back toward the galaxy center from which they came, keeping the fountain long lived. The data are consistent with major predictions of chaotic cold accretion, precipitation, and stimulated feedback models, and may trace processes fundamental to galaxy evolution at effectively all mass scales
Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry.
Purpose: Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors.
Methods: We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies.
Results: The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p < 0.001), rs9939609 (FTO) (OR 0.94, 95 % CI = 0.92â0.95, p = 4.13Eâ13), rs7903146 (TCF7L2) (OR 1.04, 95 % CI = 1.02â1.06, p = 1.26Eâ05), and rs8042680 (PRC1) (OR 0.97, 95 % CI = 0.95â0.99, p = 8.05Eâ04).
Conclusions: We have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk
Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.
BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR)â=â1.09, 95 % confidence interval (CI)â=â1.06-1.12; Pâ=â3âĂâ10(-9)), rs805510 (ORâ=â1.08, 95 % CIâ=â1.04-1.12, Pâ=â2âĂâ10(-5)), and rs1871152 (ORâ=â1.04, 95 % CIâ=â1.02-1.06; Pâ=â2âĂâ10(-4)) identified in the general populations, and rs113824616 (Pâ=â7âĂâ10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at Pâ<â0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at Pâ<â0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.UK funding includes Cancer Research UK and NIH.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13058-016-0718-
Identification of common genetic risk variants for autism spectrum disorder
Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe
TRY plant trait database â enhanced coverage and open access
Plant traitsâthe morphological, anatomical, physiological, biochemical and phenological characteristics of plantsâdetermine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of traitâbased plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traitsâalmost complete coverage for âplant growth formâ. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and traitâenvironmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives
Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia
Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40â31.03, P = 1.36 Ă 10â54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45â6.96, P = 8.75 Ă 10â19). Both risk alleles are observed at a low frequency among controls (~2â3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy
Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study
Background
The association of fitness with cancer risk is not clear.
Methods
We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (Nâ=â72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.
Results
After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5âml O2â
minâ1â
kgâ1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HRâ=â0.81, 95% CI: 0.73â0.89), colorectal (0.94, 0.90â0.99), and breast cancer (0.96, 0.92â0.99). In MR analyses, a 0.5âSD increase in genetically predicted O2â
minâ1â
kgâ1 fat-free mass was associated with a lower risk of breast cancer (ORâ=â0.92, 95% CI: 0.86â0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated.
Discussion
Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention
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