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- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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- Downey, Harriet, et al.
(författare)
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Training future generations to deliver evidence-based conservation and ecosystem management
- 2021
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Ingår i: Ecological Solutions and Evidence. - : Wiley. - 2688-8319. ; 2:1
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Forskningsöversikt (refereegranskat)abstract
- 1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis.2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice.3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses.4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.
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- Lopez-Dominguez, R, et al.
(författare)
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Transcription Factor Activity Inference in Systemic Lupus Erythematosus
- 2021
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Ingår i: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with diverse clinical manifestations. Although most of the SLE-associated loci are located in regulatory regions, there is a lack of global information about transcription factor (TFs) activities, the mode of regulation of the TFs, or the cell or sample-specific regulatory circuits. The aim of this work is to decipher TFs implicated in SLE. Methods: In order to decipher regulatory mechanisms in SLE, we have inferred TF activities from transcriptomic data for almost all human TFs, defined clusters of SLE patients based on the estimated TF activities and analyzed the differential activity patterns among SLE and healthy samples in two different cohorts. The Transcription Factor activity matrix was used to stratify SLE patients and define sets of TFs with statistically significant differential activity among the disease and control samples. Results: TF activities were able to identify two main subgroups of patients characterized by distinct neutrophil-to-lymphocyte ratio (NLR), with consistent patterns in two independent datasets—one from pediatric patients and other from adults. Furthermore, after contrasting all subgroups of patients and controls, we obtained a significant and robust list of 14 TFs implicated in the dysregulation of SLE by different mechanisms and pathways. Among them, well-known regulators of SLE, such as STAT or IRF, were found, but others suggest new pathways that might have important roles in SLE. Conclusions: These results provide a foundation to comprehend the regulatory mechanism underlying SLE and the established regulatory factors behind SLE heterogeneity that could be potential therapeutic targets.
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