| 1. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)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. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 3. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 4. |
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IMPROVER D2.2 Report of criteria for evaluating resilience
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In the recent years, the focus has moved from critical infrastructure protection to that of resilience. But how do we know whether a critical infrastructure is resilient or not, how can it be evaluated, measured and enhanced? Drawing on, combining and developing the ideas of the existing literature and practices, the current report develops a holistic, easy-to-use and computable methodology to evaluate critical infrastructure resilience, called Critical Infrastructure Resilience Index (CIRI). The methodology is applicable to all types of critical infrastructure, including a possibility to tailor it to the specific needs of different sectors, facilities and hazard scenarios. The proposed methodology is especially suitable for organizational and technological resilience evaluation, but permits including also elements of societal resilience indicators to the evaluations. The methodology is based on four levels of hierarchically organized indicators. Level 1 consists of the phases well known from the so-called crisis management cycle. Under these phases, we find sets of Level 2 rather generic indicators. Thus under level 1 ‘Prevention’, for instance, we may find a Level 2 indicator such as ‘Resilient design’, further divided into Level 3 more detailed indicators such as ‘Physical robustness’, ‘Cyber robustness’, ‘Redundancy’, ‘Modularity’, and ‘Independency’. The task is to study these indicators on Level 4 in the context of concrete critical infrastructure facilities and hazard scenarios, that is, applying Level 3 indicators into concrete circumstances. The methodology then permits to transfer quantitative, semi-quantitative and qualitative evaluations of individual sector-specific resilience indicators into uniform metrics, based on process maturity levels. This in turn makes it possible to give a specific critical infrastructure, or its part, a resilience value on the scale 0-5. While the real resilience value becomes clear only when one engages in the analysis of several indicators, the methodology can be used also as a step-by-step measurement and development tool for resilience, without necessary immediately engaging in time-consuming total resilience analysis. The user of this methodology is supposed to be the operator of critical infrastructure, or part of it, in the spirit of self-auditing. In case it would be implemented in a wider scale, in cooperation between the operators and authorities, it would give the authorities a holistic picture about the respective society’s critical infrastructure resilience. In this report, we draw a concise picture of the methodology and illustrate how this methodology could be applied to a specific infrastructure and hazard scenario.
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| 5. |
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| 6. |
- Melkunaite, Laura
(författare)
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IMPROVER Deliverable 1.1 International Survey
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In recent years, the concept of resilience started to dominate strategic, operational as well as political domains of modern societies. Living in highly interconnected environment, where layers of infrastructures, people and economic interests interact creating both opportunities and vulnerabilities, different countries around the world turned towards resilience practices to reduce vulnerability of their critical infrastructures and societies. However, how can one implement resilience concepts without a comprehensive understanding of the concept itself? Focusing on the concept and practice of critical infrastructure resilience, this report provides a comprehensive overview of the existing scientific literature regarding the concept of resilience in general. It discusses the development of the concept of resilience and its application in societal, economic, ecological, organisational and critical infrastructure domains. The report provides an extensive discussion on the definition of resilience concepts, as well as information on scientific endeavours to implement and measure concepts of resilience. The report also contains detailed information on the definitions and implementation of the concepts of resilience in different continents, namely Europe, Africa, Asia, Oceania, North America and South America. Focusing on the concept of critical infrastructure resilience, it provides an overview of the existing official concepts of resilience, implementation tools, and general practices aimed at increasing organisational, societal, economic and technical resilience in different countries. To collect all the information, the IMPROVER consortium performed an extensive literature review on the use of resilience concepts. We also held a workshop with the associate partners, and conducted a set of personal interviews with critical infrastructure operators and resilience experts around the Europe. While conducting a number of case studies in different continents, we analysed existing region and state-level documents, and reports.
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| 7. |
- Sen, Partha, et al.
(författare)
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Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain
- 2013
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 34:6, s. 801-811
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Tidskriftsartikel (refereegranskat)abstract
- Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.
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| 8. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Aebersold, Ruedi, et al.
(författare)
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How many human proteoforms are there?
- 2018
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Ingår i: Nature Chemical Biology. - : NATURE PUBLISHING GROUP. - 1552-4450 .- 1552-4469. ; 14:3, s. 206-214
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Tidskriftsartikel (refereegranskat)abstract
- Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA-and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype.
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| 10. |
- Bainbridge, Wilma A., et al.
(författare)
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Memorability of photographs in subjective cognitive decline and mild cognitive impairment : Implications for cognitive assessment
- 2019
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 11, s. 610-618
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Impaired long-term memory is a defining feature of mild cognitive impairment (MCI). We tested whether this impairment is item specific, limited to some memoranda, whereas some remain consistently memorable. Methods: We conducted item-based analyses of long-term visual recognition memory. Three hundred ninety-four participants (healthy controls, subjective cognitive decline [SCD], and MCI) in the multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) were tested with images from a pool of 835 photographs. Results: We observed consistent memorability for images in healthy controls, SCD, and MCI, predictable by a neural network trained on another healthy sample. Looking at memorability differences between groups, we identified images that could successfully categorize group membership with higher success and a substantial image reduction than the original image set. Discussion: Individuals with SCD and MCI show consistent memorability for specific items, while other items show significant diagnosticity. Certain stimulus features could optimize diagnostic assessment, while others could support memory.
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