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Schwarz, A., Moller-Hackbarth, K., Ebarasi, L., Jess, D. U., Zambrano, S., Blom, H., . . . Patrakka, J. (2019). Coro2b, a podocyte protein downregulated in human diabetic nephropathy, is involved in the development of protamine sulphate-induced foot process effacement. Scientific Reports, 9, Article ID 8888.
Open this publication in new window or tab >>Coro2b, a podocyte protein downregulated in human diabetic nephropathy, is involved in the development of protamine sulphate-induced foot process effacement
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 8888Article in journal (Refereed) Published
Abstract [en]

Podocytes have an important role in the pathogenesis of diabetic nephropathy (DN). Podocyte foot process effacement, mediated largely by the actin-based cytoskeleton of foot processes, is commonly detected in DN and is believed to be a key pathogenic event in the development of proteinuria. In this study, we identified coronin 2b (Coro2b), a member of known actin-regulating proteins, the coronins, as a highly podocyte-enriched molecule located at the cytoplasmic side of the apical plasma membrane. Studies in human renal biopsies show that glomerular Coro2b expression is significantly down-regulated in patients with DN. Studies in knockout mice indicate that Coro2b is not required for the development or maintenance of the glomerular filtration barrier. Moreover, inactivation of Coro2b specifically in podocytes does not affect the outcome of nephropathy in a streptozotocin-induced diabetes model. However, Coro2b seems to modulate the reorganization of foot processes under pathological conditions as Coro2b knockout podocytes are partially protected from protamine sulfate perfusion-induced foot process effacement. Taken together, our study suggests a role for Coro2b in the pathogenesis of glomerulopathies. Further studies regarding the involvement of Coro2b in podocyte health and diseases are warranted.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Biophysics
Identifiers
urn:nbn:se:kth:diva-255183 (URN)10.1038/s41598-019-45303-y (DOI)000472136900062 ()31221975 (PubMedID)2-s2.0-85067595475 (Scopus ID)
Note

QC 20190904

Available from: 2019-09-04 Created: 2019-09-04 Last updated: 2019-09-04Bibliographically approved
Fontana, J. M., Khodus, G. R., Unnersjö Jess, D., Blom, H., Aperia, A. & Brismar, H. (2019). Spontaneous calcium activity in metanephric mesenchymal cells regulates branching morphogenesis in the embryonic kidney. The FASEB Journal, 33(3), 4089-4096
Open this publication in new window or tab >>Spontaneous calcium activity in metanephric mesenchymal cells regulates branching morphogenesis in the embryonic kidney
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2019 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 33, no 3, p. 4089-4096Article in journal (Refereed) Published
Abstract [en]

The central role of calcium signaling during development of early vertebrates is well documented, but little is known about its role in mammalian embryogenesis. We have used immunofluorescence and time-lapse calcium imaging of cultured explanted embryonic rat kidneys to study the role of calcium signaling for branching morphogenesis. In mesenchymal cells, we recorded spontaneous calcium activity that was characterized by irregular calcium transients. The calcium signals were dependent on release of calcium from intracellular stores in the endoplasmic reticulum. Down-regulation of the calcium activity, both by blocking the sarco-endoplasmic reticulum Ca2+-ATPase and by chelating cytosolic calcium, resulted in retardation of branching morphogenesis and a reduced formation of primitive nephrons but had no effect on cell proliferation. We propose that spontaneous calcium activity contributes with a stochastic factor to the self-organizing process that controls branching morphogenesis, a major determinant of the ultimate number of nephrons in the kidney.Fontana, J. M., Khodus, G. R., Unnersjo-Jess, D., Blom, H., Aperia, A., Brismar, H. Spontaneous calcium activity in metanephric mesenchymal cells regulates branching morphogenesis in the embryonic kidney.

Place, publisher, year, edition, pages
FEDERATION AMER SOC EXP BIOL, 2019
Keywords
organogenesis, nephron, calcium imaging
National Category
Biophysics
Identifiers
urn:nbn:se:kth:diva-246250 (URN)10.1096/fj.201802054R (DOI)000459794800079 ()30496703 (PubMedID)
Note

QC 20190402

Available from: 2019-04-02 Created: 2019-04-02 Last updated: 2019-04-02Bibliographically approved
Spiess, M., Hernandez-Varas, P., Oddone, A., Olofsson, H., Blom, H., Waithe, D., . . . Stromblad, S. (2018). Active and inactive beta 1 integrins segregate into distinct nanoclusters in focal adhesions. Journal of Cell Biology, 217(6), 1929-1940
Open this publication in new window or tab >>Active and inactive beta 1 integrins segregate into distinct nanoclusters in focal adhesions
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2018 (English)In: Journal of Cell Biology, ISSN 0021-9525, E-ISSN 1540-8140, Vol. 217, no 6, p. 1929-1940Article in journal (Refereed) Published
Abstract [en]

Integrins are the core constituents of cell-matrix adhesion complexes such as focal adhesions (FAs) and play key roles in physiology and disease. Integrins fluctuate between active and inactive conformations, yet whether the activity state influences the spatial organization of integrins within FAs has remained unclear. In this study, we address this question and also ask whether integrin activity may be regulated either independently for each integrin molecule or through locally coordinated mechanisms. We used two distinct superresolution microscopy techniques, stochastic optical reconstruction microscopy (STORM) and stimulated emission depletion microscopy (STED), to visualize active versus inactive beta 1 integrins. We first reveal a spatial hierarchy of integrin organization with integrin molecules arranged in nanoclusters, which align to form linear substructures that in turn build FAs. Remarkably, within FAs, active and inactive beta 1 integrins segregate into distinct nanoclusters, with active integrin nanoclusters being more organized. This unexpected segregation indicates synchronization of integrin activities within nanoclusters, implying the existence of a coordinate mechanism of integrin activity regulation.

Place, publisher, year, edition, pages
Rockefeller University Press, 2018
National Category
Cell Biology
Identifiers
urn:nbn:se:kth:diva-232634 (URN)10.1083/jcb.201707075 (DOI)000438077800009 ()29632027 (PubMedID)2-s2.0-85048128972 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme, HEALTH-F4-2010-258068Swedish Research Council, 340-2012-6001 521-2012-3180Swedish Foundation for Strategic Research Swedish Cancer SocietyEU, FP7, Seventh Framework Programme, 337191-MOTORSKnut and Alice Wallenberg FoundationScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20180731

Available from: 2018-07-31 Created: 2018-07-31 Last updated: 2018-11-20Bibliographically approved
Jess, D. U., Scott, L., Sevilla, S. Z., Patrakka, J., Blom, H. & Brismar, H. (2018). Confocal super-resolution imaging of the glomerular filtration barrier enabled by tissue expansion. Kidney International, 93(4), 1008-1013
Open this publication in new window or tab >>Confocal super-resolution imaging of the glomerular filtration barrier enabled by tissue expansion
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2018 (English)In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 93, no 4, p. 1008-1013Article in journal (Refereed) Published
Abstract [en]

The glomerular filtration barrier, has historically only been spatially resolved using electron microscopy due to the nanometer-scale dimensions of these structures. Recently, it was shown that the nanoscale distribution of proteins in the slit diaphragm can be resolved by fluorescence based stimulated emission depletion microscopy, in combination with optical clearing. Fluorescence microscopy has advantages over electron microscopy in terms of multiplex imaging of different epitopes, and also the amount of volumetric data that can be extracted from thicker samples. However, stimulated emission depletion microscopy is still a costly technique commonly not available to most life science researchers. An imaging technique with which the glomerular filtration barrier can be visualized using more standard fluorescence imaging techniques is thus desirable. Recent studies have shown that biological tissue samples can be isotropically expanded, revealing nanoscale localizations of multiple epitopes using confocal microscopy. Here we show that kidney samples can be expanded sufficiently to study the finest elements of the filtration barrier using confocal microscopy. Thus, our result opens up the possibility to study protein distributions and foot process morphology on the effective nanometer-scale.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2018
Keywords
glomerulus, imaging, podocyte, renal pathology
National Category
Atom and Molecular Physics and Optics Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:kth:diva-226201 (URN)10.1016/j.kint.2017.09.019 (DOI)000428169200029 ()29241621 (PubMedID)2-s2.0-85037568536 (Scopus ID)
Note

QC 20180518

Available from: 2018-05-18 Created: 2018-05-18 Last updated: 2019-04-10Bibliographically approved
Johansson, H. J., Vallhov, H., Holm, T., Gehrmann, U., Andersson, A., Johansson, C., . . . Scheynius, A. (2018). Extracellular nanovesicles released from the commensal yeast Malassezia sympodialis are enriched in allergens and interact with cells in human skin. Scientific Reports, 8, Article ID 9182.
Open this publication in new window or tab >>Extracellular nanovesicles released from the commensal yeast Malassezia sympodialis are enriched in allergens and interact with cells in human skin
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 9182Article in journal (Refereed) Published
Abstract [en]

Malassezia sympodialis is a dominant commensal fungi in the human skin mycobiome but is also associated with common skin disorders including atopic eczema (AE). M. sympodialis releases extracellular vesicles, designated MalaEx, which are carriers of small RNAs and allergens, and they can induce inflammatory cytokine responses. Here we explored how MalaEx are involved in hostmicrobe interactions by comparing protein content of MalaEx with that of the parental yeast cells, and by investigating interactions of MalaEx with cells in the skin. Cryo-electron tomography revealed a heterogeneous population of MalaEx. iTRAQ based quantitative proteomics identified in total 2439 proteins in all replicates of which 110 were enriched in MalaEx compared to the yeast cells. Among the MalaEx enriched proteins were two of the M. sympodialis allergens, Mala s 1 and s 7. Functional experiments indicated an active binding and internalization of MalaEx into human keratinocytes and monocytes, and MalaEx were found in close proximity of the nuclei using super-resolution fluorescence 3D-SIM imaging. Our results provides new insights into host-microbe interactions, supporting that MalaEx may have a role in the sensitization and maintenance of inflammation in AE by containing enriched amounts of allergens and with their ability to interact with skin cells.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:kth:diva-231701 (URN)10.1038/s41598-018-27451-9 (DOI)000435338900022 ()29907748 (PubMedID)2-s2.0-85048721050 (Scopus ID)
Note

QC 20180824

Available from: 2018-08-24 Created: 2018-08-24 Last updated: 2018-08-24Bibliographically approved
Bernhem, K., Blom, H. & Brismar, H. (2018). Quantification of endogenous and exogenous protein expressions of Na,K-ATPase with super-resolution PALM/STORM imaging [Letter to the editor]. PLoS ONE
Open this publication in new window or tab >>Quantification of endogenous and exogenous protein expressions of Na,K-ATPase with super-resolution PALM/STORM imaging
2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203Article in journal, Letter (Refereed) Published
Abstract [en]

Transient transfection of fluorescent fusion proteins is a key enabling technology in fluorescent microscopy to spatio-temporally map cellular protein distributions. Transient transfection of proteins may however bypass normal regulation of expression, leading to overexpression artefacts like misallocations and excess amounts. In this study we investigate the use of STORM and PALM microscopy to quantitatively monitor endogenous and exogenous protein expression. Through incorporation of an N-terminal hemagglutinin epitope to a mMaple3 fused Na,K-ATPase (α1 isoform), we analyze the spatial and quantitative changes of plasma membrane Na,K-ATPase localization during competitive transient expression. Quantification of plasma membrane protein density revealed a time dependent increase of Na,K-ATPase, but no increase in size of protein clusters. Results show that after 41h transfection, the total plasma membrane density of Na,K-ATPase increased by 63% while the endogenous contribution was reduced by 16%.

National Category
Nano Technology
Research subject
Biological Physics
Identifiers
urn:nbn:se:kth:diva-258007 (URN)10.1371/journal. pone.0195825 (DOI)
Funder
Swedish Research Council, 2013-6041Swedish Research Council, 2015-4198Swedish Foundation for Strategic Research , RIF14-0091
Note

QC 20190916

Available from: 2019-09-09 Created: 2019-09-09 Last updated: 2019-09-16Bibliographically approved
Gliga, A. R., Edoff, K., Caputo, F., Kallman, T., Blom, H., Karlsson, H. L., . . . Fadeel, B. (2017). Cerium oxide nanoparticles inhibit differentiation of neural stem cells. Scientific Reports, 7, Article ID 9284.
Open this publication in new window or tab >>Cerium oxide nanoparticles inhibit differentiation of neural stem cells
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 9284Article in journal (Refereed) Published
Abstract [en]

Cerium oxide nanoparticles (nanoceria) display antioxidant properties and have shown cytoprotective effects both in vitro and in vivo. Here, we explored the effects of nanoceria on neural progenitor cells using the C17.2 murine cell line as a model. First, we assessed the effects of nanoceria versus samarium (Sm) doped nanoceria on cell viability in the presence of the prooxidant, DMNQ. Both particles were taken up by cells and nanoceria, but not Sm-doped nanoceria, elicited a temporary cytoprotective effect upon exposure to DMNQ. Next, we employed RNA sequencing to explore the transcriptional responses induced by nanoceria or Sm-doped nanoceria during neuronal differentiation. Detailed computational analyses showed that nanoceria altered pathways and networks relevant for neuronal development, leading us to hypothesize that nanoceria inhibits neuronal differentiation, and that nanoceria and Sm-doped nanoceria both interfere with cytoskeletal organization. We confirmed that nanoceria reduced neuron specific beta 3-tubulin expression, a marker of neuronal differentiation, and GFAP, a neuroglial marker. Furthermore, using super-resolution microscopy approaches, we could show that both particles interfered with cytoskeletal organization and altered the structure of neural growth cones. Taken together, these results reveal that nanoceria may impact on neuronal differentiation, suggesting that nanoceria could pose a developmental neurotoxicity hazard.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
National Category
Neurosciences
Identifiers
urn:nbn:se:kth:diva-214501 (URN)10.1038/s41598-017-09430-8 (DOI)000408441600008 ()28839176 (PubMedID)2-s2.0-85028350787 (Scopus ID)
Note

QC 20171002

Available from: 2017-10-02 Created: 2017-10-02 Last updated: 2018-01-13Bibliographically approved
Abrahamsson, S., Blom, H., Agostinho, A., Jans, D., Jost, A., Müller, M., . . . Brismar, H. (2017). Multifocus structured illumination microscopy for fast volumetric super-resolution imaging. Biomedical Optics Express, 8(9), 4135-4140, Article ID #294866.
Open this publication in new window or tab >>Multifocus structured illumination microscopy for fast volumetric super-resolution imaging
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2017 (English)In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 8, no 9, p. 4135-4140, article id #294866Article in journal (Refereed) Published
Abstract [en]

We here report for the first time the synergistic implementation of structured illumination microscopy (SIM) and multifocus microscopy (MFM). This imaging modality is designed to alleviate the problem of insufficient volumetric acquisition speed in superresolution biological imaging. SIM is a wide-field super-resolution technique that allows imaging with visible light beyond the classical diffraction limit. Employing multifocus diffractive optics we obtain simultaneous wide-field 3D imaging capability in the SIM acquisition sequence, improving volumetric acquisition speed by an order of magnitude. Imaging performance is demonstrated on biological specimens.

Place, publisher, year, edition, pages
OSA - The Optical Society, 2017
Keywords
Fluorescence microscopy, Imaging systems, Microscopy, Superresolution, Three-dimensional microscopy, Diffraction, Fluorescence, Image reconstruction, Light, Mergers and acquisitions, Microscopic examination, Optical resolving power, Biological specimens, Imaging performance, Structured illumination microscopies (SIM), Structured illumination microscopy, Super resolution, Super resolution imaging, Volumetric acquisitions, Magnetic force microscopy
National Category
Atom and Molecular Physics and Optics Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:kth:diva-216180 (URN)10.1364/BOE.8.004135 (DOI)000409020600017 ()2-s2.0-85028755480 (Scopus ID)
Note

QC 20171106

Available from: 2017-11-06 Created: 2017-11-06 Last updated: 2017-11-06Bibliographically approved
Bollampalli, V. P., Yamashiro, L. H., Feng, X., Bierschenk, D., Gao, Y., Blom, H., . . . Rothfuchs, A. G. (2016). BCG skin infection triggers IL-1R-MyD88-dependent migration of EpCAM(low) CD11b(high) skin dendritic cells to draining lymph node during CD4(+) T-cell priming. Paper presented at International Congress of Immunology (ICI), AUG 21-26, 2016, Melbourne, AUSTRALIA. European Journal of Immunology, 46, 790-790
Open this publication in new window or tab >>BCG skin infection triggers IL-1R-MyD88-dependent migration of EpCAM(low) CD11b(high) skin dendritic cells to draining lymph node during CD4(+) T-cell priming
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2016 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 46, p. 790-790Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
National Category
Immunology
Identifiers
urn:nbn:se:kth:diva-194288 (URN)000383610401782 ()
Conference
International Congress of Immunology (ICI), AUG 21-26, 2016, Melbourne, AUSTRALIA
Note

QC 20161024

Available from: 2016-10-24 Created: 2016-10-21 Last updated: 2017-11-29Bibliographically approved
Fontana, J. M., Jess, D. U., Blom, H., Brismar, H. & Aperia, A. (2016). Role of calcium signaling for GDNF secretion, ureter branching and early nephron formation. Paper presented at Experimental Biology Meeting, APR 02-06, 2016, San Diego, CA. The FASEB Journal, 30
Open this publication in new window or tab >>Role of calcium signaling for GDNF secretion, ureter branching and early nephron formation
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2016 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 30Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
FEDERATION AMER SOC EXP BIOL, 2016
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-242657 (URN)000406444705388 ()
Conference
Experimental Biology Meeting, APR 02-06, 2016, San Diego, CA
Note

QC 201902255

Available from: 2019-02-25 Created: 2019-02-25 Last updated: 2019-02-25Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-5584-9170

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