| 1. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 5. |
- Laabei, M., et al.
(author)
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Predicting the virulence of MRSA from its genome sequence
- 2014
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In: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 24:5, s. 839-849
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Journal article (peer-reviewed)abstract
- Microbial virulence is a complex and often multifactorial phenotype, intricately linked to a pathogen's evolutionary trajectory. Toxicity, the ability to destroy host cell membranes, and adhesion, the ability to adhere to human tissues, are the major virulence factors of many bacterial pathogens, including Staphylococcus aureus. Here, we assayed the toxicity and adhesiveness of 90 MRSA (methicillin resistant S. aureus) isolates and found that while there was remarkably little variation in adhesion, toxicity varied by over an order of magnitude between isolates, suggesting different evolutionary selection pressures acting on these two traits. We performed a genome-wide association study (GWAS) and identified a large number of loci, as well as a putative network of epistatically interacting loci, that significantly associated with toxicity. Despite this apparent complexity in toxicity regulation, a predictive model based on a set of significant single nucleotide polymorphisms (SNPs) and insertion and deletions events (indels) showed a high degree of accuracy in predicting an isolate's toxicity solely from the genetic signature at these sites. Our results thus highlight the potential of using sequence data to determine clinically relevant parameters and have further implications for understanding the microbial virulence of this opportunistic pathogen.
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| 6. |
- Lindblad-Toh, Kerstin, et al.
(author)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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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.
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| 7. |
- Lee, S. D., et al.
(author)
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IDOL regulates systemic energy balance through control of neuronal VLDLR expression
- 2019
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In: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 1:11
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Journal article (peer-reviewed)abstract
- Liver X receptors limit cellular lipid uptake by stimulating the transcription of inducible degrader of the low-density lipoprotein receptor (IDOL), an E3 ubiquitin ligase that targets lipoprotein receptors for degradation. The function of IDOL in systemic metabolism is incompletely understood. Here we show that loss of IDOL in mice protects against the development of dietinduced obesity and metabolic dysfunction by altering food intake and thermogenesis. Unexpectedly, analysis of tissue-specific knockout mice revealed that IDOL affects energy balance, not through its actions in peripheral metabolic tissues (liver, adipose tissue, endothelium, intestine, and skeletal muscle) but by controlling lipoprotein receptor abundance in neurons. Single-cell RNA sequencing of the hypothalamus demonstrated that IDOL deletion altered gene expression linked to the control of metabolism. Finally, we identified very low-density lipoprotein receptor (VLDLR) rather than low-density lipoprotein receptor (LDLR) as the primary mediator of the effects of IDOL on energy balance. These data identify a role for the neuronal IDOL-VLDLR pathway in metabolic homoeostasis and diet-induced obesity.
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| 8. |
- Goytia, Susana, et al.
(author)
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Dealing with change and uncertainty within the regulatory frameworks for flood defense infrastructure in selected European countries
- 2016
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In: Ecology and Society. - 1708-3087. ; 21:4
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Journal article (peer-reviewed)abstract
- Whereas existing literature on the interactions among law, adaptive governance, and resilience in the water sector often focuses on quality or supply issues, this paper addresses adaptation in national water laws in relation to increasing flood risks. In particular, this paper analyzes the extent to which legal rules governing flood defense infrastructure in a selection of European countries (England, France, Sweden, and The Netherlands) allow for response and adaptation to change and uncertainty. Although there is evidence that the legal rules on the development of new infrastructure require that changing conditions be considered, the adaptation of existing infrastructure is a more complicated matter. Liability rules fail to adequately address damages resulting from causes external to the action or inaction of owners and managers, in particular extreme events. A trend toward clearer, and in some cases, increased public powers to ensure the safety of flood defense infrastructure is observed. The paper concludes that legal rules should ensure not only that decisions to build flood defenses are based on holistic and future-oriented assessments, but also that this is reflected in the implementation and operation of these structures.
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| 9. |
- Priest, Sally J., et al.
(author)
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The European union approach to flood risk management and improving societal resilience : Lessons from the implementation of the Floods Directive in six European countries
- 2016
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In: Ecology and Society. - 1708-3087. ; 21:4
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Journal article (peer-reviewed)abstract
- Diversity in flood risk management approaches is often considered to be a strength. However, in some national settings, and especially for transboundary rivers, variability and incompatibility of approaches can reduce the effectiveness of flood risk management. Placed in the context of increasing flood risks, as well as the potential for flooding to undermine the European Union’s sustainable development goals, a desire to increase societal resilience to flooding has prompted the introduction of a common European Framework. We provide a legal and policy analysis of the implementation of the Floods Directive (2007/60/EC) in six countries: Belgium (Flemish region), England, France, the Netherlands, Poland, and Sweden. Evaluation criteria from existing legal and policy literature frame the study of the Directive and its effect on enhancing or constraining societal resilience by using an adaptive governance approach. These criteria are initially used to analyze the key components of the EU approach, before providing insight of the implementation of the Directive at a national level. Similarities and differences in the legal translation of European goals into existing flood risk management are analyzed alongside their relative influence on policy and practice. The research highlights that the effect of the Floods Directive on increasing societal resilience has been nationally variable, in part because of its focus on procedural obligations, rather than on more substantive requirements. Analysis shows that despite a focus on transboundary river basin management, existing traditions of flood risk management have overridden objectives to harmonize flood risk management in some cases. The Directive could be strengthened by requiring more stringent cooperation and providing the competent authorities in international river basin districts with more power. Despite some shortcomings in directly affecting flood risk outcomes, the Directive has positively stimulated discussion and flood risk management planning in countries that were perhaps lagging behind
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| 10. |
- Cordeddu, Viviana, et al.
(author)
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Activating Mutations Affecting the Dbl Homology Domain of SOS2 Cause Noonan Syndrome
- 2015
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In: Human Mutation. - : WILEY-BLACKWELL. - 1059-7794 .- 1098-1004. ; 36:11, s. 1080-1087
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Journal article (peer-reviewed)abstract
- The RASopathies constitute a family of autosomal-dominant disorders whose major features include facial dysmorphism, cardiac defects, reduced postnatal growth, variable cognitive deficits, ectodermal and skeletal anomalies, and susceptibility to certain malignancies. Noonan syndrome (NS), the commonest RASopathy, is genetically heterogeneous and caused by functional dysregulation of signal transducers and regulatory proteins with roles in the RAS/extracellular signal-regulated kinase (ERK) signal transduction pathway. Mutations in known disease genes account for approximately 80% of affected individuals. Here, we report that missense mutations altering Son of Sevenless, Drosophila, homolog 2 (SOS2), which encodes a RAS guanine nucleotide exchange factor, occur in a small percentage of subjects with NS. Four missense mutations were identified in five unrelated sporadic cases and families transmitting NS. Disease-causing mutations affected three conserved residues located in the Dbl homology (DH) domain, of which two are directly involved in the intramolecular binding network maintaining SOS2 in its autoinhibited conformation. All mutations were found to promote enhanced signaling from RAS to ERK. Similar to NS-causing SOS1 mutations, the phenotype associated with SOS2 defects is characterized by normal development and growth, as well as marked ectodermal involvement. Unlike SOS1 mutations, however, those in SOS2 are restricted to the DH domain.
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