| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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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.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Predicting the virulence of MRSA from its genome sequence
- 2014
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 24:5, s. 839-849
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)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.
(författare)
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IDOL regulates systemic energy balance through control of neuronal VLDLR expression
- 2019
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Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 1:11
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Ecology and Society. - 1708-3087. ; 21:4
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Ecology and Society. - 1708-3087. ; 21:4
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Activating Mutations Affecting the Dbl Homology Domain of SOS2 Cause Noonan Syndrome
- 2015
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Ingår i: Human Mutation. - : WILEY-BLACKWELL. - 1059-7794 .- 1098-1004. ; 36:11, s. 1080-1087
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Tidskriftsartikel (refereegranskat)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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| 11. |
- Dieperink, Carel, et al.
(författare)
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Managing urban flood resilience as a multilevel governance challenge : an analysis of required multilevel coordination mechanisms
- 2018
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Ingår i: Ecology and Society. - : Resilience Alliance. - 1708-3087. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- In both academic literature and flood risk management practices, it is argued that governance initiatives are needed to enhance the flood resilience of urban agglomerations. Multiple levels of governance will be involved in this activity. However, thus far, the literature has hardly addressed what mechanisms are required to coordinate the different levels of managing urban flood resilience, and what factors account for these mechanisms. Our aim is to address this knowledge gap. Here, we examine six in-depth case studies undertaken in urban agglomerations in different European countries: Dordrecht, the Netherlands; Hull, UK; Geraardsbergen, Belgium; Karlstad, Sweden; Wroclaw, Poland; and Nice, France. The case studies reveal the ways in which multiple levels of governance are involved in managing urban flood resilience. Coordination among governance levels is achieved by proactive policy entrepreneurs, the use of bridging concepts, clear rules, and the provision of resources. These mechanisms seem to be universally applicable, but their characteristics appear to be highly dependent on more general institutional, economic, geographical, and cultural contextual factors.
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| 12. |
- Driessen, Peter P. J., et al.
(författare)
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Governance Strategies for Improving Flood Resilience in the Face of Climate Change
- 2018
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Ingår i: Water. - : MDPI. - 2073-4441. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- Flooding is the most common of all natural disasters and accounts for large numbers of casualties and a high amount of economic damage worldwide. To be ‘flood resilient’, countries should have sufficient capacity to resist, the capacity to absorb and recover, and the capacity to transform and adapt. Based on international comparative research, we conclude that six key governance strategies will enhance ‘flood resilience’ and will secure the necessary capacities. These strategies pertain to: (i) the diversification of flood risk management approaches; (ii) the alignment of flood risk management approaches to overcome fragmentation; (iii) the involvement, cooperation, and alignment of both public and private actors in flood risk management; (iv) the presence of adequate formal rules that balance legal certainty and flexibility; (v) the assurance of sufficient financial and other types of resources; (vi) the adoption of normative principles that adequately deal with distributional effects. These governance strategies appear to be relevant across different physical and institutional contexts. The findings may also hold valuable lessons for the governance of climate adaptation more generally.
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| 13. |
- Hegger, Dries, et al.
(författare)
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Toward more flood resilience : Is a diversification of flood risk management strategies the way forward?
- 2016
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Ingår i: Ecology and Society. - 1708-3087. ; 21:4
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Tidskriftsartikel (refereegranskat)abstract
- European countries face increasing flood risks because of urbanization, increase of exposure and damage potential, and the effects of climate change. In literature and in practice, it is argued that a diversification of strategies for flood risk management (FRM), including flood risk prevention (through proactive spatial planning), flood defense, flood risk mitigation, flood preparation, and flood recovery, makes countries more flood resilient. Although this thesis is plausible, it should still be empirically scrutinized. We aim to do this. Drawing on existing literature we operationalize the notion of “flood resilience” into three capacities: capacity to resist; capacity to absorb and recover; and capacity to transform and adapt. Based on findings from the EU FP7 project STAR-FLOOD, we explore the degree of diversification of FRM strategies and related flood risk governance arrangements at the national level in Belgium, England, France, the Netherlands, Poland, and Sweden, as well as these countries’ achievement in terms of the three capacities. We found that the Netherlands and to a lesser extent Belgium have a strong capacity to resist, France a strong capacity to absorb and recover, and especially England a high capacity to transform and adapt. Having a diverse portfolio of FRM strategies in place may be conducive to high achievements related to the capacities to absorb/recover and to transform and adapt. Hence, we conclude that diversification of FRM strategies contributes to resilience. However, the diversification thesis should be nuanced in the sense that there are different ways to be resilient. First, the three capacities imply different rationales and normative starting points for flood risk governance, the choice between which is inherently political. Second, we found trade-offs between the three capacities, e.g., being resistant seems to lower the possibility to be absorbent. Third, to explain countries’ achievements in terms of resilience, the strategies’ feasibility in specific physical circumstances and their fit in existing institutional contexts (appropriateness), as well as the establishment of links between strategies, through bridging mechanisms, have also been shown to be crucial factors. We provide much needed reflection on the implications of this diagnosis for governments, private parties, and citizens who want to increase flood resilience
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| 14. |
- Höppner, Marc P., et al.
(författare)
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An Improved Canine Genome and a Comprehensive Catalogue of Coding Genes and Non-Coding Transcripts
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3, s. e91172-
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Tidskriftsartikel (refereegranskat)abstract
- The domestic dog, Canis familiaris, is a well-established model system for mapping trait and disease loci. While the original draft sequence was of good quality, gaps were abundant particularly in promoter regions of the genome, negatively impacting the annotation and study of candidate genes. Here, we present an improved genome build, canFam3.1, which includes 85 MB of novel sequence and now covers 99.8% of the euchromatic portion of the genome. We also present multiple RNA-Sequencing data sets from 10 different canine tissues to catalog similar to 175,000 expressed loci. While about 90% of the coding genes previously annotated by EnsEMBL have measurable expression in at least one sample, the number of transcript isoforms detected by our data expands the EnsEMBL annotations by a factor of four. Syntenic comparison with the human genome revealed an additional similar to 3,000 loci that are characterized as protein coding in human and were also expressed in the dog, suggesting that those were previously not annotated in the EnsEMBL canine gene set. In addition to,20,700 high-confidence protein coding loci, we found,4,600 antisense transcripts overlapping exons of protein coding genes, similar to 7,200 intergenic multi-exon transcripts without coding potential, likely candidates for long intergenic non-coding RNAs (lincRNAs) and,11,000 transcripts were reported by two different library construction methods but did not fit any of the above categories. Of the lincRNAs, about 6,000 have no annotated orthologs in human or mouse. Functional analysis of two novel transcripts with shRNA in a mouse kidney cell line altered cell morphology and motility. All in all, we provide a much-improved annotation of the canine genome and suggest regulatory functions for several of the novel non-coding transcripts.
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| 15. |
- Liu, Yuwen, et al.
(författare)
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A simple, cross-linked collagen tissue substitute for corneal implantation
- 2006
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 47:5, s. 1869-1875
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To develop a simple corneal substitute from crosslinked collagen. METHODS. Porcine type I collagen (10%, pH 5), was mixed with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The final homogenous solution was molded to corneal dimensions, cured, and then implanted into rabbits and minipigs by lamellar keratoplasty. The implants were followed for up to 6 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, topography and esthesiometry for nerve function. Histopathologic examinations were also performed on rabbit corneas harvested after 6 months. RESULTS. Cross-linked collagen (refractive index, 1.35) had optical clarity superior to human corneas. Implanted into rabbit and porcine corneas, only 1 of 24 of the surgical corneas showed a slight haze at 6 months after surgery. All other implants showed no adverse reactions and remained optically clear. Topography showed a smooth surface and a profile similar to that of the contralateral nonsurgical eye. The implanted matrices promoted regeneration of corneal cells, tear film, and nerves. Touch sensitivity was restored, indicating some restoration of function. The corneas with implants showed no significant loss of thickness and demonstrated stable host- graft integration. CONCLUSIONS. Collagen can be adequately stabilized, using water soluble carbodiimides as protein cross-linking reagents, in the fabrication of corneal matrix substitutes for implantation. The simple cross-linking methodology would allow for easy fabrication of matrices for transplantation in centers where there is a shortage of corneas, or where there is need for temporary patches to repair perforations in emergency situations. Copyright © Association for Research in Vision and Ophthalmology.
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| 16. |
- Rhind, Nicholas, et al.
(författare)
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Comparative Functional Genomics of the Fission Yeasts
- 2011
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 332:6032, s. 930-936
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Tidskriftsartikel (refereegranskat)abstract
- The fission yeast clade-comprising Schizosaccharomyces pombe, S. octosporus, S. cryophilus, and S. japonicus-occupies the basal branch of Ascomycete fungi and is an important model of eukaryote biology. A comparative annotation of these genomes identified a near extinction of transposons and the associated innovation of transposon-free centromeres. Expression analysis established that meiotic genes are subject to antisense transcription during vegetative growth, which suggests a mechanism for their tight regulation. In addition, trans-acting regulators control new genes within the context of expanded functional modules for meiosis and stress response. Differences in gene content and regulation also explain why, unlike the budding yeast of Saccharomycotina, fission yeasts cannot use ethanol as a primary carbon source. These analyses elucidate the genome structure and gene regulation of fission yeast and provide tools for investigation across the Schizosaccharomyces clade.
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| 17. |
- Wang, Ying, et al.
(författare)
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Clonally expanding smooth muscle cells promote atherosclerosis by escaping efferocytosis and activating the complement cascade
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 117:27, s. 15818-15826
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis is the process underlying heart attack and stroke. Despite decades of research, its pathogenesis remains unclear. Dogma suggests that atherosclerotic plaques expand primarily via the accumulation of cholesterol and inflammatory cells. However, recent evidence suggests that a substantial portion of the plaque may arise from a subset of "dedifferentiated" vascular smooth muscle cells (SMCs) which proliferate in a clonal fashion. Herein we use multicolor lineage-tracing models to confirm that the mature SMC can give rise to a hyperproliferative cell which appears to promote inflammation via elaboration of complement-dependent anaphylatoxins. Despite being extensively opsonized with prophagocytic complement fragments, we find that this cell also escapes immune surveillance by neighboring macrophages, thereby exacerbating its relative survival advantage. Mechanistic studies indicate this phenomenon results from a generalized opsoninsensing defect acquired by macrophages during polarization. This defect coincides with the noncanonical up-regulation of so-called don't eat me molecules on inflamed phagocytes, which reduces their capacity for programmed cell removal (PrCR). Knockdown or knockout of the key antiphagocytic molecule CD47 restores the ability of macrophages to sense and clear opsonized targets in vitro, allowing for potent and targeted suppression of clonal SMC expansion in the plaque in vivo. Because integrated clinical and genomic analyses indicate that similar pathways are active in humans with cardiovascular disease, these studies suggest that the clonally expanding SMC may represent a translational target for treating atherosclerosis.
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| 18. |
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