| 1. |
- Ali, Zaheer, et al.
(författare)
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Photoreceptor Degeneration Accompanies Vascular Changes in a Zebrafish Model of Diabetic Retinopathy
- 2020
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Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 61:2
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness worldwide in the working-age population, and the incidence is rising. Until now it has been difficult to define initiating events and disease progression at the molecular level, as available diabetic rodent models do not present the full spectrum of neural and vascular pathologies. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor pdx1 were previously shown to display a diabetic phenotype from larval stages through adulthood. In this study, pdx1 mutants were examined for retinal vascular and neuronal pathology to demonstrate suitability of these fish for modeling DR. METHODS. Vessel morphology was examined in pdx1 mutant and control fish expressing the fli1a:EGFP transgene. We further characterized vascular and retinal phenotypes in mutants and controls using immunohistochemistry, histology, and electron microscopy. Retinal function was assessed using electroretinography. RESULTS. Pdx1 mutants exhibit clear vascular phenotypes at 2 months of age, and disease progression, including arterial vasculopenia, capillary tortuosity, and hypersprouting, could be detected at stages extending over more than 1 year. Neural-retinal pathologies are consistent with photoreceptor dysfunction and loss, but do not progress to blindness. CONCLUSIONS. This study highlights pdx1 mutant zebrafish as a valuable complement to rodent and other mammalian models of DR, in particular for research into the mechanistic interplay of diabetes with vascular and neuroretinal disease. They are furthermore suited for molecular studies to identify new targets for treatment of early as well as late DR.
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| 2. |
- Farkas, Julia, et al.
(författare)
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Impact of TiO2 nanoparticles on freshwater bacteria from three Swedish lakes
- 2015
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 535, s. 85-93
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Tidskriftsartikel (refereegranskat)abstract
- Due to the rapidly rising production and usage of nano-enabled products, aquatic environments are increasingly exposed to engineered nanoparticles (ENPs), causing concerns about their potential negative effects. In this study we assessed the effects of uncoated titanium dioxide nanoparticles (TiO(2)NPs) on the growth and activity of bacterial communities of three Swedish lakes featuring different chemical characteristics such as dissolved organic carbon (DOC) concentration, pH and elemental composition. TiO2NP exposure concentrations were 15, 100, and 1000 mu g L-1, and experiments were performed in situ under three light regimes: darkness, photosynthetically active radiation (PAR), and ambient sunlight including UV radiation (UVR). The nanoparticles were most stable in lake water with high DOC and low chemical element concentrations. At the highest exposure concentration (1000 mu g L-1 TiO2NP) the bacterial abundance was significantly reduced in all lake waters. In the medium and high DOC lake waters, exposure concentrations of 100 mu g L-1 TiO2NP caused significant reductions in bacterial abundance. The cell-specific bacterial activity was significantly enhanced at high TiO2NP exposure concentrations, indicating the loss of nanoparticle-sensitive bacteria and a subsequent increased activity by tolerant ones. No UV-induced phototoxic effect of TiO2NP was found in this study. We conclude that in freshwater lakes with high DOC and low chemical element concentrations, uncoated TiO(2)NPs show an enhanced stability and can significantly reduce bacterial abundance at relatively low exposure concentrations.
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| 3. |
- Hayashi, Hisamitsu, et al.
(författare)
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Molecular organization and fine structure of the human tectorial membrane : is it replenished?
- 2015
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 362:3, s. 513-527
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Tidskriftsartikel (refereegranskat)abstract
- Auditory sensitivity and frequency resolution depend on the physical properties of the basilar membrane in combination with outer hair cell-based amplification in the cochlea. The physiological role of the tectorial membrane (TM) in hair cell transduction has been controversial for decades. New insights into the TM structure and function have been gained from studies of targeted gene disruption. Several missense mutations in genes regulating the human TM structure have been described with phenotypic expressions. Here, we portray the remarkable gradient structure and molecular organization of the human TM. Ultrastructural analysis and confocal immunohistochemistry were performed in freshly fixed human cochleae obtained during surgery. Based on these findings and recent literature, we discuss the role of human TMs in hair cell activation. Moreover, the outcome proposes that the α-tectorin-positive amorphous layer of the human TM is replenished and partly undergoes regeneration during life.
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| 4. |
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| 5. |
- Thaler, Marlene, et al.
(författare)
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Visualization and Analysis of Superparamagnetic Iron Oxide Nanoparticles in the Inner Ear by Light Microscopy and Energy Filtered TEM
- 2011
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Ingår i: Nanomedicine: Nanotechnology, Biology, and Medicine. - : Elsevier BV. - 1549-9634. ; 7:3, s. 360-369
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles as potential carriers for local drug transfer are an alternative to systemic drug delivery into the inner ear. We report on the first in vitro tests of a new ferrogel consisting of superparamagnetic iron oxide nanoparticles (SPIONs) and a Pluronic (R) F127 (PF127) copolymer. Pluronic copolymers possess a unique viscosity-adjustable property that makes PF127 gels easy to handle compared to conventional cross-linked hydrogels. This ferrogel was successfully tested in cadaver human temporal bones as well as in organotypic explant cultures of mouse inner ears. SPIONs were identified by light microscopy and localized with different imaging modes in energy-filtered transmission electron microscopy. Our approach shows a promising possibility to use iron oxide nanoparticles, which are suitable for visualization and characterization at both the light- and electron-microscopic levels. From the Clinical Editor: The authors report the first in vitro tests of a new ferrogel consisting of superparamagnetic iron oxide nanoparticles (SPIONs) and a Pluronic (R) F127 (PF127) copolymer for drug delivery in the inner ear, demonstrasting a promising possibility to use iron oxide nanoparticles, which are suitable for visualization and characterization at both the light- and electron-microscopic levels.
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| 6. |
- Wunderer, Julia, et al.
(författare)
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A mechanism for temporary bioadhesion
- 2019
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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. ; 116:10, s. 4297-4306
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Tidskriftsartikel (refereegranskat)abstract
- The flatworm Macrostomum lignano features a duo-gland adhesive system that allows it to repeatedly attach to and release from substrates in seawater within a minute. However, little is known about the molecules involved in this temporary adhesion. In this study, we show that the attachment of M. lignano relies on the secretion of two large adhesive proteins, M. lignano adhesion protein 1 (Mlig-ap1) and Mlig-ap2. We revealed that both proteins are expressed in the adhesive gland cells and that their distribution within the adhesive footprints was spatially restricted. RNA interference knockdown experiments demonstrated the essential function of these two proteins in flatworm adhesion. Negatively charged modified sugars in the surrounding water inhibited flatworm attachment, while positively charged molecules impeded detachment. In addition, we found that M. lignano could not adhere to strongly hydrated surfaces. We propose an attachment-release model where Mlig-ap2 attaches to the substrate and Mlig-ap1 exhibits a cohesive function. A small negatively charged molecule is secreted that interferes with Mlig-ap1, inducing detachment. These findings are of relevance for fundamental adhesion science and efforts to mitigate biofouling. Further, this model of flatworm temporary adhesion may serve as the starting point for the development of synthetic reversible adhesion systems for medicinal and industrial applications.
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| 7. |
- Zeng, Fan, et al.
(författare)
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Identifying adhesive components in a model tunicate
- 2019
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Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : ROYAL SOC. - 0962-8436 .- 1471-2970. ; 374:1784
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Tidskriftsartikel (refereegranskat)abstract
- Tunicates populate a great variety of marine underwater substrates worldwide and represent a significant concern in marine shipping and aquaculture. Adhesives are secreted from the anterior papillae of their swimming larvae, which attach and metamorphose into permanently adhering, filter-feeding adults. We recently described the cellular composition of the sensory adhesive organ of the model tunicate Ciona intestinalis in great detail. Notably, the adhesive secretions of collocytes accumulate at the tip of the organ and contain glycoproteins. Here, we further explore the components of adhesive secretions and have screened for additional specificities that may influence adhesion or cohesion of the Ciona glue, including other carbohydrate moieties, catechols and substrate properties. We found a distinct set of sugar residues in the glue recognized by specific lectins with little overlap to other known marine adhesives. Surprisingly, we also detect catechol residues that likely originate from an adjacent cellular reservoir, the test cells. Furthermore, we provide information on substrate preferences where hydrophobicity outperforms charge in the attachment. Finally, we can influence the settlement process by the addition of hydrophilic heparin. The further analysis of tunicate adhesive strategies should provide a valuable knowledge source in designing physiological adhesives or green antifoulants. This article is part of the theme issue Transdisciplinary approaches to the study of adhesion and adhesives in biological systems.
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