| 1. |
- Aad, G., et al.
(författare)
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- 2013
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swepub:Mat__t (refereegranskat)
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| 2. |
- Aad, G., et al.
(författare)
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- 2013
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swepub:Mat__t (refereegranskat)
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| 3. |
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| 4. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 5. |
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| 6. |
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| 7. |
- Defourny, Jean, et al.
(författare)
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Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells
- 2013
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 1438-
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Tidskriftsartikel (refereegranskat)abstract
- Hearing requires an optimal afferent innervation of sensory hair cells by spiral ganglion neurons in the cochlea. Here we report that complementary expression of ephrin-A5 in hair cells and EphA4 receptor among spiral ganglion neuron populations controls the targeting of type I and type II afferent fibres to inner and outer hair cells, respectively. In the absence of ephrin-A5 or EphA4 forward signalling, a subset of type I projections aberrantly overshoot the inner hair cell layer and invade the outer hair cell area. Lack of type I afferent synapses impairs neurotransmission from inner hair cells to the auditory nerve. By contrast, radial shift of type I projections coincides with a gain of presynaptic ribbons that could enhance the afferent signalling from outer hair cells. Ephexin-1, cofilin and myosin light chain kinase act downstream of EphA4 to induce type I spiral ganglion neuron growth cone collapse. Our findings constitute the first identification of an Eph/ephrin-mediated mutual repulsion mechanism responsible for specific sorting of auditory projections in the cochlea.
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| 8. |
- Fazey, Ioan, et al.
(författare)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 9. |
- Kalkofen, Denis, et al.
(författare)
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Tools for Teaching Mining Students in Virtual Reality based on 360° Video Experiences
- 2020
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Ingår i: 2020 IEEE Conference on Virtual Reality and 3D User Interfaces Abstracts and Workshops. - : IEEE. ; , s. 455-459
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In recent years, Virtual Reality (VR) technology has found their way into higher education. Its power lays in its ability to provide immersive three-dimensional (3D) experiences that help conveying educational content whilst providing rich interaction possibilities. Especially in mining engineering education, VR has high potential to reshape the provided learning content. Field trips, i.e. mine visits, are an integral part of the education and necessary to transfer knowledge to students. However, field trips are time and cost intensive and mines often have tight entry regulations. As a result, the number of field trips is limited. VR-based field trips offer a considerable alternative presupposed they replicate the complex mining environment realistically. In addition, VR mines have the advantage of taking students close to events (e.g. explosions) that are impossible to demonstrate in a real mine. However, generating realistic 3D content for VR still involves complex, and thus time consuming tasks. Therefore, we present the design of a VR Framework for teaching mining students based on 360° video data, its evaluation in three different lectures, and its extension based on the feedback we received from students and teachers from four different universities.
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| 10. |
- Richter, Katharina N., et al.
(författare)
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Glyoxal as an alternative fixative to formaldehyde in immunostaining and super-resolution microscopy
- 2018
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Ingår i: EMBO Journal. - : WILEY. - 0261-4189 .- 1460-2075. ; 37:1, s. 139-159
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Tidskriftsartikel (refereegranskat)abstract
- Paraformaldehyde (PFA) is the most commonly used fixative for immunostaining of cells, but has been associated with various problems, ranging from loss of antigenicity to changes in morphology during fixation. We show here that the small dialdehyde glyoxal can successfully replace PFA. Despite being less toxic than PFA, and, as most aldehydes, likely usable as a fixative, glyoxal has not yet been systematically tried in modern fluorescence microscopy. Here, we tested and optimized glyoxal fixation and surprisingly found it to be more efficient than PFA-based protocols. Glyoxal acted faster than PFA, cross-linked proteins more effectively, and improved the preservation of cellular morphology. We validated glyoxal fixation in multiple laboratories against different PFA-based protocols and confirmed that it enabled better immunostainings for a majority of the targets. Our data therefore support that glyoxal can be a valuable alternative to PFA for immunostaining.
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| 11. |
- Tranebjærg, Lisbeth, et al.
(författare)
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The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management
- 2018
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Ingår i: Human Genetics. - : Springer. - 0340-6717 .- 1432-1203. ; 137:2, s. 111-127
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Tidskriftsartikel (refereegranskat)abstract
- Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS) is a rare clinically distinct syndrome caused by a single dominant missense mutation, c.2452G>A, p.Glu818Lys, in ATP1A3, encoding the neuron-specific alpha subunit of the Na+/K+-ATPase α3. Allelic mutations cause the neurological diseases rapid dystonia Parkinsonism and alternating hemiplegia of childhood, disorders which do not encompass hearing or visual impairment. We present detailed clinical phenotypic information in 18 genetically confirmed patients from 11 families (10 previously unreported) from Denmark, Sweden, UK and Germany indicating a specific type of hearing impairment-auditory neuropathy (AN). All patients were clinically suspected of CAPOS and had hearing problems. In this retrospective analysis of audiological data, we show for the first time that cochlear outer hair cell activity was preserved as shown by the presence of otoacoustic emissions and cochlear microphonic potentials, but the auditory brainstem responses were grossly abnormal, likely reflecting neural dyssynchrony. Poor speech perception was observed, especially in noise, which was beyond the hearing level obtained in the pure tone audiograms in several of the patients presented here. Molecular modelling and in vitro electrophysiological studies of the specific CAPOS mutation were performed. Heterologous expression studies of α3 with the p.Glu818Lys mutation affects sodium binding to, and release from, the sodium-specific site in the pump, the third ion-binding site. Molecular dynamics simulations confirm that the structure of the C-terminal region is affected. In conclusion, we demonstrate for the first time evidence for auditory neuropathy in CAPOS syndrome, which may reflect impaired propagation of electrical impulses along the spiral ganglion neurons. This has implications for diagnosis and patient management. Auditory neuropathy is difficult to treat with conventional hearing aids, but preliminary improvement in speech perception in some patients suggests that cochlear implantation may be effective in CAPOS patients.
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| 12. |
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| 13. |
- Zhou, Xiao-Hong, et al.
(författare)
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Neurocan is dispensable for brain development
- 2001
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Ingår i: Molecular and Cellular Biology. - 0270-7306. ; 21:17, s. 5970-5978
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Tidskriftsartikel (refereegranskat)abstract
- Neurocan is a component of the extracellular matrix in brain. Due to its inhibition of neuronal adhesion and outgrowth in vitro and its expression pattern in vivo it was suggested to play an important role in axon guidance and neurite growth. To study the role of neurocan in brain development we generated neurocan-deficient mice by targeted disruption of the neurocan gene. These mice are viable and fertile and have no obvious deficits in reproduction and general performance. Brain anatomy, morphology, and ultrastructure are similar to those of wild-type mice. Perineuronal nets surrounding neurons appear largely normal. Mild deficits in synaptic plasticity may exist, as maintenance of late-phase hippocampal long-term potentiation is reduced. These data indicate that neurocan has either a redundant or a more subtle function in the development of the brain.
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| 14. |
- Åkerström, Tobias, et al.
(författare)
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Activating mutations in CTNNB1 in aldosterone producing adenomas
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Primary aldosteronism (PA) is the most common cause of secondary hypertension with a prevalenceof 5–10% in unreferred hypertensive patients. Aldosterone producing adenomas (APAs) constitutea large proportion of PA cases and represent a surgically correctable form of the disease. The WNTsignaling pathway is activated in APAs. In other tumors, a frequent cause of aberrant WNT signaling ismutation in the CTNNB1 gene coding for β-catenin. Our objective was to screen for CTNNB1 mutationsin a well-characterized cohort of 198 APAs. Somatic CTNNB1 mutations were detected in 5.1% of thetumors, occurring mutually exclusive from mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. Allof the observed mutations altered serine/threonine residues in the GSK3β binding domain in exon 3.The mutations were associated with stabilized β-catenin and increased AXIN2 expression, suggestingactivation of WNT signaling. By CYP11B2 mRNA expression, CYP11B2 protein expression, and directmeasurement of aldosterone in tumor tissue, we confirmed the ability for aldosterone production. Thisreport provides compelling evidence that aberrant WNT signaling caused by mutations in CTNNB1 occurin APAs. This also suggests that other mechanisms that constitutively activate the WNT pathway maybe important in APA formation.
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| 15. |
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| 16. |
- Åkerström, Tobias, et al.
(författare)
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Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas.
- 2015
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 22:5, s. 735-744
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Tidskriftsartikel (refereegranskat)abstract
- Aldosterone-producing adenomas (APAs) are found in 1.5-3.0% of hypertensive patients in primary care and can be cured by surgery. Elucidation of genetic events may improve our understanding of these tumors and ultimately improve patient care. Approximately 40% of APAs harbor a missense mutation in the KCNJ5 gene. More recently, somatic mutations in CACNA1D, ATP1A1 and ATP2B3, also important for membrane potential/intracellular Ca(2) (+) regulation, were observed in APAs. In this study, we analyzed 165 APAs for mutations in selected regions of these genes. We then correlated mutational findings with clinical and molecular phenotype using transcriptome analysis, immunohistochemistry and semiquantitative PCR. Somatic mutations in CACNA1D in 3.0% (one novel mutation), ATP1A1 in 6.1% (six novel mutations) and ATP2B3 in 3.0% (two novel mutations) were detected. All observed mutations were located in previously described hotspot regions. Patients with tumors harboring mutations in CACNA1D, ATP1A1 and ATP2B3 were operated at an older age, were more often male and had tumors that were smaller than those in patients with KCNJ5 mutated tumors. Microarray transcriptome analysis segregated KCNJ5 mutated tumors from ATP1A1/ATP2B3 mutated tumors and those without mutation. We observed significant transcription upregulation of CYP11B2, as well as the previously described glomerulosa-specific gene NPNT, in ATP1A1/ATP2B3 mutated tumors compared to KCNJ5 mutated tumors. In summary, we describe novel somatic mutations in proteins regulating the membrane potential/intracellular Ca(2) (+) levels, and also a distinct mRNA and clinical signature, dependent on genetic alteration.
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| 17. |
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| 18. |
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| 19. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 20. |
- Aad, G., et al.
(författare)
-
- 2011
-
Tidskriftsartikel (refereegranskat)
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| 21. |
- Aad, G., et al.
(författare)
-
- 2012
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swepub:Mat__t (refereegranskat)
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| 22. |
- Aad, G., et al.
(författare)
-
- 2011
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swepub:Mat__t (refereegranskat)
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| 23. |
- Aad, G., et al.
(författare)
-
- 2012
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swepub:Mat__t (refereegranskat)
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| 24. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 25. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 26. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 27. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 28. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 29. |
- Aad, G., et al.
(författare)
-
- 2011
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swepub:Mat__t (refereegranskat)
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| 30. |
- Aad, G., et al.
(författare)
-
- 2011
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swepub:Mat__t (refereegranskat)
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| 31. |
- Aad, G., et al.
(författare)
-
- 2011
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swepub:Mat__t (refereegranskat)
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| 32. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 33. |
- Aad, G., et al.
(författare)
-
- 2012
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swepub:Mat__t (refereegranskat)
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| 34. |
- Aad, G., et al.
(författare)
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- 2012
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Tidskriftsartikel (refereegranskat)
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| 35. |
- Aad, G., et al.
(författare)
-
- 2012
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swepub:Mat__t (refereegranskat)
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| 36. |
- Aad, G., et al.
(författare)
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- 2012
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Tidskriftsartikel (refereegranskat)
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| 37. |
- Aad, G., et al.
(författare)
-
- 2012
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swepub:Mat__t (refereegranskat)
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| 38. |
- Aad, G., et al.
(författare)
-
- 2011
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swepub:Mat__t (refereegranskat)
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| 39. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 40. |
- Aad, G., et al.
(författare)
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- 2011
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Tidskriftsartikel (refereegranskat)
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| 41. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 42. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 43. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 44. |
- Aad, G., et al.
(författare)
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- 2012
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Tidskriftsartikel (refereegranskat)
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| 45. |
- Aad, G., et al.
(författare)
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- 2011
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Tidskriftsartikel (refereegranskat)
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| 46. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 47. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 48. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 49. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t
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| 50. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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