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| 2. |
- Hildebrand, S, et al.
(författare)
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The E-cadherin/AmotL2 complex organizes actin filaments required for epithelial hexagonal packing and blastocyst hatching
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 9540-
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial cells connect via cell-cell junctions to form sheets of cells with separate cellular compartments. These cellular connections are essential for the generation of cellular forms and shapes consistent with organ function. Tissue modulation is dependent on the fine-tuning of mechanical forces that are transmitted in part through the actin connection to E-cadherin as well as other components in the adherens junctions. In this report we show that p100 amotL2 forms a complex with E-cadherin that associates with radial actin filaments connecting cells over multiple layers. Genetic inactivation or depletion of amotL2 in epithelial cells in vitro or zebrafish and mouse in vivo, resulted in the loss of contractile actin filaments and perturbed epithelial packing geometry. We further showed that AMOTL2 mRNA and protein was expressed in the trophectoderm of human and mouse blastocysts. Genetic inactivation of amotL2 did not affect cellular differentiation but blocked hatching of the blastocysts from the zona pellucida. These results were mimicked by treatment with the myosin II inhibitor blebbistatin. We propose that the tension generated by the E-cadherin/AmotL2/actin filaments plays a crucial role in developmental processes such as epithelial geometrical packing as well as generation of forces required for blastocyst hatching.
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| 3. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 5. |
- Hultin, S, et al.
(författare)
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AmotL2 integrates polarity and junctional cues to modulate cell shape
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 7548-
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Tidskriftsartikel (refereegranskat)abstract
- The assembly of individual epithelial or endothelial cells into a tight cellular sheet requires stringent control of cell packing and organization. These processes are dependent on the establishment and further integration of cellular junctions, the cytoskeleton and the formation of apical-basal polarity. However, little is known how these subcellular events are coordinated. The (Angiomotin) Amot protein family consists of scaffold proteins that interact with junctional cadherins, polarity proteins and the cytoskeleton. In this report, we have studied how these protein complexes integrate to control cellular shapes consistent with organ function. Using gene-inactivating studies in zebrafish and cell culture systems in vitro, we show that Par3 to be essential for localization of AmotL2 to cellular junctions to associate with VE/E-cadherin and subsequently the organization of radial actin filaments. Our data provide mechanistic insight in how critical processes such as aortic lumen expansion as well as epithelial packing into hexagonal shapes are controlled.
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| 6. |
- Mattheos, N., et al.
(författare)
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Developing implant dentistry education in Europe : the continuum from undergraduate to postgraduate education and continuing professional development
- 2014
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Ingår i: European journal of dental education. - : John Wiley & Sons. - 1396-5883 .- 1600-0579. ; 18:S1, s. 4-10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Implant dentistry is a treatment modality which has mainstream clinical practice of comprehensive care, which however is not adequately represented in the undergraduate dental curricula. A consensus workshop organised by ADEE in 2008, set the benchmarks for the knowledge and competences a modern dental practitioner must possess with regard to implant dentistry, as well as defined undergraduate and postgraduate pathways for the acquisition of these competences. Today, 5 years later, there exist several challenges for the implementation of these benchmarks in both undergraduate curricula but also post-graduation educational pathways. Methods: A consensus workshop was organised by ADEE, bringing together 48 opinion leaders, including academic teachers of all disciplines related to implant dentistry, specialists, representatives of relevant scientific and professional associations, as well as industry delegates. The objectives of the workshop were to evaluate the existing scientific literature, reported experience and best practices in order to identify potential and limitations for the implementation of implant dentistry in the undergraduate curriculum, as well produce recommendations for the optimal educational structures for postgraduate programmes and continuing professional development. Results: The scientific committee conducted two European-wide questionnaire surveys to better document the current state of education in implant dentistry. Upon completion of the surveys, reviewers were appointed to produce three scientific review papers, identifying current achievements and future challenges. Finally, during the 3 days of the workshop, all the evidence was reviewed and the main conclusions and recommendations that were adopted by all participants are reported in the present Consensus Paper. Conclusions: Implementation of implant dentistry in the undergraduate curriculum has improved significantly, but still lags behind the benchmarks set in 2008 and the diversity between institutions remains big. At the post-graduation level, there is currently a wide diversity of courses and pathways towards competences related to implant dentistry and there is at present a great need for quality assurance, as well as standardisation and transparency of the learning outcomes.
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| 8. |
- Rohdin, Cecilia, et al.
(författare)
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Presence of thoracic and lumbar vertebral malformations in pugs with and without chronic neurological deficits
- 2018
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Ingår i: The Veterinary Journal. - : Elsevier BV. - 1090-0233 .- 1532-2971. ; 241, s. 24-30
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Tidskriftsartikel (refereegranskat)abstract
- Congenital vertebral malformations (CVMs) are common in brachycephalic dogs such as the pug, and are often considered incidental findings. However, specific CVMs have been suggested to be associated with neurological deficits in pugs. The objective of this study was to investigate the clinical importance of CVMs in the pug by comparing computed tomography studies of the thoracolumbar spine from pugs without neurological deficits with those from pugs with a confirmed T3-L3 spinal cord lesion and neurological deficits consistent with a chronic T3-L3 myelopathy. A total of 57 pugs were recruited into the study from Sweden (n=33), United Kingdom (n=21) and Norway (n = 3); 30 with neurological deficits and 27 without. Focal T3-L3 pathology was confirmed in all pugs with neurological deficits by magnetic resonance imaging (n = 29) and/or pathology (n = 15). Computed tomography studies of the thoracolumbar spine from pugs with and without neurological deficits were compared to investigate possible associations between presentation of neurological deficits consistent with chronic T3-L3 pathology and signalment variables, presence of CVMs and type of CVMs. Congenital vertebral malformations were as common in pugs with, as in pugs without, neurological deficits. Regardless of neurological status, the majority of pugs (96%) presented with one or more CVM. An association between presence, or type of CVM in the T1-L3 vertebral column, and neurological deficits consistent with T3-L3 pathology could not be confirmed.
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| 9. |
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| 10. |
- Hultin, Sara, et al.
(författare)
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AmotL2 links VE-cadherin to contractile actin fibres necessary for aortic lumen expansion
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The assembly of individual endothelial cells into multicellular tubes is a complex morphogenetic event in vascular development. Extracellular matrix cues and cell-cell junctional communication are fundamental to tube formation. Together they determine the shape of endothelial cells and the tubular structures that they ultimately form. Little is known regarding how mechanical signals are transmitted between cells to control cell shape changes during morphogenesis. Here we provide evidence that the scaffold protein amotL2 is needed for aortic vessel lumen expansion. Using gene inactivation strategies in zebrafish, mouse and endothelial cell culture systems, we show that amotL2 associates to the VE-cadherin adhesion complex where it couples adherens junctions to contractile actin fibres. Inactivation of amotL2 dissociates VE-cadherin from cytoskeletal tensile forces that affect endothelial cell shape. We propose that the VE-cadherin/amotL2 complex is responsible for transmitting mechanical force between endothelial cells for the coordination of cellular morphogenesis consistent with aortic lumen expansion and function.
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