| 1. |
- Kattge, Jens, et al.
(author)
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TRY plant trait database - enhanced coverage and open access
- 2020
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In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Journal article (peer-reviewed)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine 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 trait-based 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 traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental 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.
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| 2. |
- Ursini-Siegel, Josie, et al.
(author)
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Receptor Tyrosine Kinase Signaling Favors a Protumorigenic State in Breast Cancer Cells by Inhibiting the Adaptive Immune Response
- 2010
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In: Cancer Research. - 1538-7445. ; 70:20, s. 7776-7787
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Journal article (peer-reviewed)abstract
- Using transgenic mouse models of breast cancer that ablate Src homology and collagen A ( ShcA) expression or oncogene-coupled ShcA signaling, we previously showed that this adaptor is critical for mammary tumor onset and progression. We now provide the first evidence that ShcA regulates mammary tumorigenesis, in part, through its ability to regulate the adaptive immune response. Inactivation of ShcA signaling within tumor cells results in extensive CD4(+) T-cell infiltration and induction of a humoral immune response in mammary tumors. This is associated with a robust CTL response in preneoplastic lesions that are deficient in ShcA signaling. Moreover, mammary tumor progression of ShcA-deficient hyperplasias is accelerated in a T cell-deficient background. We also uncover a clinically relevant correlation between high ShcA expression and low CTL infiltration in human breast cancers. Finally, we define a novel ShcA-regulated immune signature that functions as an independent prognostic marker of survival in human epidermal growth factor receptor 2(+) and basal breast cancers. We reveal a novel role for tumor cell-derived ShcA in the establishment and maintenance of an immunosuppressive state. Cancer Res; 70(20); 7776-87. (C) 2010 AACR.
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| 3. |
- Anney, Richard, et al.
(author)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Journal article (peer-reviewed)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 4. |
- Falster, Daniel, et al.
(author)
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AusTraits, a curated plant trait database for the Australian flora
- 2021
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In: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
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Journal article (peer-reviewed)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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| 5. |
- Krzyzanowska, Agnieszka, et al.
(author)
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Development, Validation, and Clinical Utility of a Six-gene Signature to Predict Aggressive Prostate Cancer
- 2023
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In: European Urology Focus. - 2405-4569. ; 9:6, s. 983-991
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Journal article (peer-reviewed)abstract
- Background: Molecular signatures in prostate cancer (PCa) tissue can provide useful prognostic information to improve the understanding of a patient's risk of harbouring aggressive disease. Objective: To develop and validate a gene signature that adds independent prognostic information to clinical parameters for better treatment decisions and patient management. Design, setting, and participants: Expression of 14 genes was evaluated in radical prostatectomy (RP) tissue from an Irish cohort of PCa patients (n = 426). A six-gene molecular risk score (MRS) was identified with strong prognostic performance to predict adverse pathology (AP) at RP or biochemical recurrence (BCR). The MRS was combined with the Cancer of the Prostate Risk Assessment (CAPRA) score, to create a molecular and clinical risk score (MCRS), and validated in a Swedish cohort (n = 203). Outcome measurements and statistical analysis: The primary AP outcome was assessed by the likelihood ratio statistics and area under the receiver operating characteristics curves (AUC) from logistic regression models. The secondary time to BCR outcome was assessed by likelihood ratio statistics and C-indexes from Cox proportional hazard regression models. Results and limitations: The six-gene signature was significantly (p < 0.0001) prognostic and added significant prognostic value to clinicopathological features for AP and BCR outcomes. For both outcomes, both the MRS and the MCRS increased the AUC/C-index when added to European Association of Urology (EAU) and CAPRA scores. Limitations include the retrospective nature of this study. Conclusions: The six-gene signature has strong performance for the prediction of AP and BCR in an independent clinical validation study. MCRS improves prognostic evaluation and can optimise patient management after RP. Patient summary: We found that the expression panel of six genes can help predict whether a patient is likely to have a disease recurrence after radical prostatectomy surgery.
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| 6. |
- Pinto, Dalila, et al.
(author)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Journal article (peer-reviewed)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 7. |
- Prencipe, Maria, et al.
(author)
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Relationship Between Serum Response Factor and Androgen Receptor in Prostate Cancer
- 2015
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In: The Prostate. - : Wiley. - 0270-4137. ; 75:15, s. 1704-1717
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Journal article (peer-reviewed)abstract
- BACKGROUND. Serum response factor (SRF) is an important transcription factor in castrate-resistant prostate cancer (CRPC). Since CRPC is associated with androgen receptor (AR) hypersensitivity, we investigated the relationship between SRF and AR. MATERIALS AND METHODS. Transcriptional activity was assessed by luciferase assay. Cell proliferation was measured by MTT and flow cytometry. Protein expression in patients was assessed by immunohistochemistry. RESULTS. To investigate AR involvement in SRF response to androgen, AR expression was down-regulated using siRNA. This resulted in the abrogation of SRF induction post-DHT. Moreover, DHT stimulation failed to induce SRF transcriptional activity in AR-negative PC346 DCC cells, which was only restored following AR over-expression. Next, SRF expression was down-regulated by siRNA, resulting in AR increased transcriptional activity in castrate-resistant LNCaP Abl cells but not in the parental LNCaP. This negative feedback loop in the resistant cells was confirmed by immunohistochemistry which showed a negative correlation between AR and SRF expression in CRPC bone metastases and a positive correlation in androgen-naive prostatectomies. Cell proliferation was next assessed following SRF inhibition, demonstrating that SRF inhibition is more effective than AR inhibition in castrate-resistant cells. CONCLUSION. Our data support SRF as a promising therapeutic target in combination with current treatments. (C) 2015 Wiley Periodicals, Inc.
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| 8. |
- Prencipe, Maria, et al.
(author)
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Role of serum response factor expression in prostate cancer biochemical recurrence
- 2018
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In: The Prostate. - : Wiley. - 0270-4137. ; 78:10, s. 724-730
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Journal article (peer-reviewed)abstract
- BACKGROUND: Up to a third of prostate cancer patients fail curative treatment strategies such as surgery and radiation therapy in the form of biochemical recurrence (BCR) which can be predictive of poor outcome. Recent clinical trials have shown that men experiencing BCR might benefit from earlier intervention post-radical prostatectomy (RP). Therefore, there is an urgent need to identify earlier prognostic biomarkers which will guide clinicians in making accurate diagnosis and timely decisions on the next appropriate treatment. The objective of this study was to evaluate Serum Response Factor (SRF) protein expression following RP and to investigate its association with BCR.MATERIALS AND METHODS: SRF nuclear expression was evaluated by immunohistochemistry (IHC) in TMAs across three international radical prostatectomy cohorts for a total of 615 patients. Log-rank test and Kaplan-Meier analyses were used for BCR comparisons. Stepwise backwards elimination proportional hazard regression analysis was used to explore the significance of SRF in predicting BCR in the context of other clinical pathological variables. Area under the curve (AUC) values were generated by simulating repeated random sub-samples.RESULTS: Analysis of the immunohistochemical staining of benign versus cancer cores showed higher expression of nuclear SRF protein expression in cancer cores compared with benign for all the three TMAs analysed (P < 0.001, n = 615). Kaplan-Meier curves of the three TMAs combined showed that patients with higher SRF nuclear expression had a shorter time to BCR compared with patients with lower SRF expression (P < 0.001, n = 215). Together with pathological T stage T3, SRF was identified as a predictor of BCR using stepwise backwards elimination proportional hazard regression analysis (P = 0.0521). Moreover ROC curves and AUC values showed that SRF was better than T stage in predicting BCR at year 3 and 5 following radical prostatectomy, the combination of SRF and T stage had a higher AUC value than the two taken separately.CONCLUSIONS: SRF assessment by IHC following RP could be useful in guiding clinicians to better identify patients for appropriate follow-up and timely treatment.
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| 9. |
- Ryan, Denise, et al.
(author)
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Topoisomerase I Amplification in Melanoma is Associated with More Advanced Tumours and Poor Prognosis
- 2010
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In: Pigment Cell and Melanoma Research. - 1755-148X. ; 23:4, s. 542-553
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Journal article (peer-reviewed)abstract
- Summary In this study, we used array-comparative genomic hybridisation (aCGH) and fluorescent in situ hybridisation (FISH) to examine genetic aberrations in melanoma cell lines and tissues. aCGH revealed that the most frequent genetic changes found in melanoma cell lines were amplifications on chromosomes 7p and 20q, along with disruptions on Chr 9, 10, 11, 12, 22 and Y. Validation of the results using FISH on tissue microarrays (TMAs) identified TOP1 as being amplified in melanoma tissues. TOP1 amplification was detected in a high percentage (33%) of tumours and was associated with thicker, aggressive tumours. These results show that TOP1 amplification is associated with advanced tumours and poor prognosis in melanoma. These observations open the possibility that TOP1-targeted therapeutics may be of benefit in a particular subgroup of advanced stage melanoma patients.
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| 10. |
- Agnarsdóttir, Margrét, 1970-, et al.
(author)
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Protein Biomarkers in Malignant Melanoma: An Image Analysis-Based Study on Melanoma Markers of Potential Clinical Relevance
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Other publication (other academic/artistic)abstract
- The thickness of a primary malignant melanoma tumor is the most important prognostic indicator for a patient with primary cutaneous malignant melanoma. To optimize the management and treatment of melanoma patients there is an unmet need to identify characteristics that can further stratify melanoma patients into high or low risk for progressive disease. Despite numerous studies no single marker has yet been shown to add significant prognostic information. An algorithmic approach, combining data from several markers provides an attractive model to identify patients of increased risk of dying from malignant melanoma. The primary aim of the present study was to analyze the correlation between clinical outcome and protein expression patterns of multiple proteins in malignant melanoma tumors using immunohistochemistry and tissue microarrays. Candidate proteins were identified based on a selective and differential expression pattern in melanoma tumors and tested in a cohort of 143 melanoma patients. Protein expression was analyzed using both manual scoring and automated image analysis-based algorithms. We found no single marker of prognosis that was independent of tumor thickness. When combining potential prognostic markers we could define a prognostic index, based on RBM3, MITF, SOX10 and Ki-67, that was independent of tumor thickness in multivariate analysis. Our findings suggest that a good prognosis signature can be identified in melanoma patients with tumors showing a low fraction of Ki-67 positive tumor cells and a high fraction of RBM3 positive tumor cells combined with low intensity levels of SOX10 and MITF.
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