| 1. |
- Lindblad-Toh, Kerstin, et al.
(author)
-
Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
-
Journal article (peer-reviewed)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- O'Brien, Sallyarm L., et al.
(author)
-
CENP-F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer
- 2007
-
In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 120:7, s. 1434-1443
-
Journal article (peer-reviewed)abstract
- DNA microarrays have the potential to classify tumors according to their transcriptome. Tissue microarrays (TMAs) facilitate the validation of biomarkers by offering a high-throughput approach to sample analysis. We reanalyzed a high profile breast cancer DNA microarray dataset containing 96 tumor samples using a powerful statistical approach, between group analyses. Among the genes we identified was centromere protein-F (CENP-F), a gene associated with poor prognosis. In a published follow-up breast cancer DNA microarray study, comprising 295 tumour samples, we found that CENP-F upregulation was significantly associated with worse overall survival (p < 0.001) and reduced metastasis-free survival (p < 0.001). To validate and expand upon these findings, we used 2 independent breast cancer patient cohorts represented on TMAs. CENP-F protein expression was evaluated by immunohistochemistry in 91 primary breast cancer samples from cohort I and 289 samples from cohort II. CENP-F correlated with markers of aggressive tumor behavior including ER negativity and high tumor grade. In cohort I, CENP-F was significantly associated with markers of CIN including cyclin E, increased telomerase activity, c-Myc amplification and aneuploidy. In cohort II CENP-F correlated with VEGFR2, phosphorylated Ets-2 and Ki67, and in multivariate analysis, was an independent predictor of worse breast cancer-specific survival (p = 0.036) and overall survival (p = 0.040). In conclusion, we identified CENP-F as a biomarker associated with poor outcome in breast cancer and showed several novel associations of biological significance. (c) 2007 Wiley-Liss, Inc.
|
|
| 5. |
- Lanigan, Fiona, et al.
(author)
-
Increased claudin-4 expression is associated with poor prognosis and high tumour grade in breast cancer
- 2009
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:9, s. 2088-2097
-
Journal article (peer-reviewed)abstract
- The role of intercellular tight junctions in breast epithelia[ cells is traditionaliy thought to be in maintaining polarity and barrier function. However, claudin-4, a tight junction protein, is overexpressed in breast tumour cells compared to normal epithelial cells, which generally corresponds to a loss in polarity. The aim of this study was to investigate the distribution and potential clinical value of claudin-4 in breast cancer, and to evaluate its usefulness as a prognostic and predictive biomarker. Expression of claudin-4 was initially examined by Western blot analysis in a cohort of 88 breast tumours, and was found to correlate positively with tumour grade and negatively with ER. Claudin-4 expression was then evaluated by immunohistochemistry in a larger cohort of 299 tumours represented on a tissue microarray. Claudin-4 expression correlated positively with tumour grade and Hcr2, and negatively with ER. High claudin-4 expression was also associated with worse breast cancer-specific survival (p = 0.0031), recurrence-free survival (P = 0.025) and overall survival (p = 0.034). Multivariate analysis revealed that claudin-4 independently predicted survival in the entire cohort (HR 1.95; 95%CI 1.01-3.79; p = 0.047) and in the ER positive subgroup treated with adjuvant tamoxifen (FIR 4.34; 95%C1 1.14-16.53; p = 0.032). This relationship between increased claudin-4 expression and adverse outcome was validated at the mRNA level in a DNA microarray dataset of 295 breast tumours. We conclude that high levels of claudin-4 protein are associated with adverse outcome in breast cancer patients, including the subgroup of patients treated with adjuvant tamoxifen. (C) 2008 Wiley-Liss, Inc.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Hegarty, Peter, 1971, et al.
(author)
-
When Almost All Sets are Difference Dominated
- 2009
-
In: Random Structures and Algorithms. - : Wiley. - 1042-9832 .- 1098-2418. ; 35:1, s. 118-136
-
Journal article (peer-reviewed)abstract
- We investigate the relationship between the sizes of the sum and difference sets attached to a subset of {0,1,...,N}, chosen randomly according to a binomial model with parameter p(N), with N^{-1} = o(p(N)). We show that the random subset is almost surely difference dominated, as N --> oo, for any choice of p(N) tending to zero, thus confirming a conjecture of Martin and O'Bryant. The proofs use recent strong concentration results. Furthermore, we exhibit a threshold phenomenon regarding the ratio of the size of the difference- to the sumset. If p(N) = o(N^{-1/2}) then almost all sums and differences in the random subset are almost surely distinct, and in particular the difference set is almost surely about twice as large as the sumset. If N^{-1/2} = o(p(N)) then both the sum and difference sets almost surely have size (2N+1) - O(p(N)^{-2}), and so the ratio in question is almost surely very close to one. If p(N) = c N^{-1/2} then as c increases from zero to infinity (i.e., as the threshold is crossed), the same ratio almost surely decreases continuously from two to one according to an explicitly given function of c. We also extend our results to the comparison of the generalized difference sets attached to an arbitrary pair of binary linear forms. For certain pairs of forms f and g, we show that there in fact exists a sharp threshold at c_{f,g} N^{-1/2}, for some computable constant c_{f,g}, such that one form almost surely dominates below the threshold, and the other almost surely above it. The heart of our approach involves using different tools to obtain strong concentration of the sizes of the sum and difference sets about their mean values, for various ranges of the parameter p.
|
|
| 11. |
- Kurganskiy, Alexander, et al.
(author)
-
Predicting the severity of the grass pollen season and the effect of climate change in Northwest Europe
- 2021
-
In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:13
-
Journal article (peer-reviewed)abstract
- Allergic rhinitis is an inflammation in the nose caused by overreaction of the immune system to allergens in the air. Managing allergic rhinitis symptoms is challenging and requires timely intervention. The following are major questions often posed by those with allergic rhinitis: How should I prepare for the forthcoming season? How will the season's severity develop over the years? No country yet provides clear guidance addressing these questions. We propose two previously unexplored approaches for forecasting the severity of the grass pollen season on the basis of statistical and mechanistic models. The results suggest annual severity is largely governed by preseasonal meteorological conditions. The mechanistic model suggests climate change will increase the season severity by up to 60%, in line with experimental chamber studies. These models can be used as forecasting tools for advising individuals with hay fever and health care professionals how to prepare for the grass pollen season.
|
|
| 12. |
- McKeen, Hayley D., et al.
(author)
-
The emerging role of FK506-binding proteins as cancer biomarkers: a focus on FKBPL
- 2011
-
In: Biochemical Society Transactions. - 1470-8752 .- 0300-5127. ; 39, s. 663-668
-
Conference paper (peer-reviewed)abstract
- FKBPs (FK506-binding proteins) have long been recognized as key regulators of the response to immunosuppressant drugs and as co-chaperones of steroid receptor complexes. More recently, evidence has emerged suggesting that this diverse protein family may also represent cancer biomarkers owing to their roles in cancer progression and response to treatment. FKBPL (FKBP-like) is a novel FKBP with roles in GR (glucocorticoid receptor), AR (androgen receptor) and ER (oestrogen receptor) signalling. FKBPL binds Hsp90 (heat-shock protein 90) and modulates translocation, transcriptional activation and phosphorylation of these steroid receptors. It has been proposed as a novel prognostic and predictive biomarker, where high levels predict for increased recurrence-free survival in breast cancer patients and enhanced sensitivity to endocrine therapy. Since this protein family has roles in a plethora of signalling pathways, its members represent novel prognostic markers and therapeutic targets for cancer diagnosis and treatment.
|
|
| 13. |
- Nelson, Laura, et al.
(author)
-
FKBPL: a marker of good prognosis in breast cancer.
- 2015
-
In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:14, s. 12209-12223
-
Journal article (peer-reviewed)abstract
- FK506-binding protein-like (FKBPL) has established roles as an anti-tumor protein, with a therapeutic peptide based on this protein, ALM201, shortly entering phase I/II clinical trials. Here, we evaluated FKBPL's prognostic ability in primary breast cancer tissue, represented on tissue microarrays (TMA) from 3277 women recruited into five independent retrospective studies, using immunohistochemistry (IHC). In a meta-analysis, FKBPL levels were a significant predictor of BCSS; low FKBPL levels indicated poorer breast cancer specific survival (BCSS) (hazard ratio (HR) = 1.30, 95% confidence interval (CI) 1.14-1.49, p < 0.001). The prognostic impact of FKBPL remained significant after adjusting for other known prognostic factors (HR = 1.25, 95% CI 1.07-1.45, p = 0.004). For the sub-groups of 2365 estrogen receptor (ER) positive patients and 1649 tamoxifen treated patients, FKBPL was significantly associated with BCSS (HR = 1.34, 95% CI 1.13-1.58, p < 0.001, and HR = 1.25, 95% CI 1.04-1.49, p = 0.02, respectively). A univariate analysis revealed that FKBPL was also a significant predictor of relapse free interval (RFI) within the ER positive patient group, but it was only borderline significant within the smaller tamoxifen treated patient group (HR = 1.32 95% CI 1.05-1.65, p = 0.02 and HR = 1.23 95% CI 0.99-1.54, p = 0.06, respectively). The data suggests a role for FKBPL as a prognostic factor for BCSS, with the potential to be routinely evaluated within the clinic.
|
|
| 14. |
- Rowney, Francis M, et al.
(author)
-
Environmental DNA reveals links between abundance and composition of airborne grass pollen and respiratory health
- 2021
-
In: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 31:9, s. 4-2003
-
Journal article (peer-reviewed)abstract
- Grass (Poaceae) pollen is the most important outdoor aeroallergen,1 exacerbating a range of respiratory conditions, including allergic asthma and rhinitis ("hay fever").2-5 Understanding the relationships between respiratory diseases and airborne grass pollen with a view to improving forecasting has broad public health and socioeconomic relevance. It is estimated that there are over 400 million people with allergic rhinitis6 and over 300 million with asthma, globally,7 often comorbidly.8 In the UK, allergic asthma has an annual cost of around US$ 2.8 billion (2017).9 The relative contributions of the >11,000 (worldwide) grass species (C. Osborne et al., 2011, Botany Conference, abstract) to respiratory health have been unresolved,10 as grass pollen cannot be readily discriminated using standard microscopy.11 Instead, here we used novel environmental DNA (eDNA) sampling and qPCR12-15 to measure the relative abundances of airborne pollen from common grass species during two grass pollen seasons (2016 and 2017) across the UK. We quantitatively demonstrate discrete spatiotemporal patterns in airborne grass pollen assemblages. Using a series of generalized additive models (GAMs), we explore the relationship between the incidences of airborne pollen and severe asthma exacerbations (sub-weekly) and prescribing rates of drugs for respiratory allergies (monthly). Our results indicate that a subset of grass species may have disproportionate influence on these population-scale respiratory health responses during peak grass pollen concentrations. The work demonstrates the need for sensitive and detailed biomonitoring of harmful aeroallergens in order to investigate and mitigate their impacts on human health.
|
|
| 15. |
|
|
