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- Blom, Hans, et al.
(författare)
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Spatial Distribution of DARPP-32 in Dendritic Spines
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9, s. e75155-
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Tidskriftsartikel (refereegranskat)abstract
- The phosphoprotein DARPP-32 (dopamine and cyclic adenosine 3́, 5́-monophosphate-regulated phosphoprotein, 32 kDa) is an important component in the molecular regulation of postsynaptic signaling in neostriatum. Despite the importance of this phosphoprotein, there is as yet little known about the nanoscale distribution of DARPP-32. In this study we applied superresolution stimulated emission depletion microscopy (STED) to assess the expression and distribution of DARPP-32 in striatal neurons. Primary culture of striatal neurons were immunofluorescently labeled for DARPP-32 with Alexa-594 and for the dopamine D1 receptor (D1R) with atto-647N. Dual-color STED microscopy revealed discrete localizations of DARPP-32 and D1R in the spine structure, with clustered distributions in both head and neck. Dissected spine structures reveal that the DARPP-32 signal rarely overlapped with the D1R signal. The D1R receptor is positioned in an "aggregated" manner primarily in the spine head and to some extent in the neck, while DARPP-32 forms several neighboring small nanoclusters spanning the whole spine structure. The DARPP-32 clusters have a mean size of 52 +/- 6 nm, which is close to the resolution limit of the microscope and corresponds to the physical size of a few individual phosphoprotein immunocomplexes. Dissection of synaptic proteins using superresolution microscopy gives possibilities to reveal in better detail biologically relevant information, as compared to diffraction-limited microscopy. In this work, the dissected postsynaptic topology of the DARPP-32 phosphoprotein provides strong evidence for a compartmentalized and confined distribution in dendritic spines. The protein topology and the relatively low copy number of phosphoprotein provides a conception of DARPP-32's possibilities to fine-tune the regulation of synaptic signaling, which should have an impact on the performance of the neuronal circuits in which it is expressed.
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| 2. |
- Hellkvist, L., et al.
(författare)
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High dose pollen intralymphatic immunotherapy: Two RDBPC trials question the benefit of dose increase
- 2022
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Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 77:3, s. 883-96
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Tidskriftsartikel (refereegranskat)abstract
- Background The same dosing schedule, 1000 SQ-U times three, with one-month intervals, have been evaluated in most trials of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis (AR). The present studies evaluated if a dose escalation in ILIT can enhance the clinical and immunological effects, without compromising safety. Methods Two randomized double-blind placebo-controlled trials of ILIT for grass pollen-induced AR were performed. The first included 29 patients that had recently ended 3 years of SCIT and the second contained 39 not previously vaccinated patients. An up-dosage of 1000-3000-10,000 (5000 + 5000 with 30 minutes apart) SQ-U with 1 month in between was evaluated. Results Doses up to 10,000 SQ-U were safe after recent SCIT. The combined symptom-medication scores (CSMS) were reduced by 31% and the grass-specific IgG4 levels in blood were doubled. In ILIT de novo, the two first patients that received active treatment developed serious adverse reactions at 5000 SQ-U. A modified up-dosing schedule; 1000-3000-3000 SQ-U appeared to be safe but failed to improve the CSMS. Flow cytometry analyses showed increased activation of lymph node-derived dendritic but not T cells. Quality of life and nasal provocation response did not improve in any study. Conclusion Intralymphatic immunotherapy in high doses after SCIT appears to further reduce grass pollen-induced seasonal symptoms and may be considered as an add-on treatment for patients that do not reach full symptom control after SCIT. Up-dosing schedules de novo with three monthly injections that exceeds 3000 SQ-U should be avoided.
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| 3. |
- Hjalmarsson, E, et al.
(författare)
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A five-year open follow up of a randomized, double-blind placebo-controlled trial of intralymphatic immunotherapy for birch and grass reveals remaining beneficial effects
- 2022
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Ingår i: Journal of investigational allergology & clinical immunology. - : Esmon Publicidad, SA. - 1018-9068. ; , s. 0-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intralymphatic immunotherapy (ILIT) has been proposed as a novel, less time-consuming alternative to conventional allergy immunotherapy (AIT). Few previous studies have evaluated its long-term effects. The objective of the study was to complete a 5-year follow-up of a previously performed randomized, double-blind placebo-controlled trial of ILIT for a combination of birch and grass allergens. Methods: Fifty-eight patients with allergic rhinitis were treated with either placebo or a combination of ALK Alutard Birch and Grass 1000 SQ-U, three intralymphatic injections with one-month intervals. A year after the vaccination, symptoms induced by nasal provocation were significantly reduced. 5-6 years later, 20 out of 26 actively treated patients were followed up with a nasal provocation test (NPT), seasonal registration of the combined symptoms and medications score (CSMS), IgE and IgG4 levels in the blood and immunological markers in blood and lymph nodes and compared with 13 unvaccinated controls Results: The ILIT induced reduction in the NPT response seen in year one could not be convincingly reproduced in year five. The new CSMS scores were markedly lower among the previously treated patients than for the control group. Further, grass-specific IgG4 was increased, grass-specific IgE decreased, FcεR1 on basophils reduced, and the amount of memory T-cells in the lymph nodes increased. Conclusion: The combination of seasonal derived clinical data and immunological parameters supports the notion of a long-lasting effect of ILIT. These data support the concept of ILIT as a good alternative to traditional AIT in pollen-induced allergic rhinitis.
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| 4. |
- Kronawitter, C. X., et al.
(författare)
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Titanium incorporation into hematite photoelectrodes : theoretical considerations and experimental observations
- 2014
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Ingår i: Energy & Environmental Science. - : Royal Society of Chemistry (RSC). - 1754-5692 .- 1754-5706. ; 7:10, s. 3100-3121
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Tidskriftsartikel (refereegranskat)abstract
- A theoretical and experimental perspective on the role of titanium impurities in hematite (alpha-Fe2O3) nanostructured photoelectrodes for solar fuel synthesis devices is provided. Titanium incorporation is a known correlate to efficiency enhancement in alpha-Fe2O3 cc photoanodes for solar water oxidation; here the relevant literature and the latest advances are presented and various proposed mechanisms for enhancement are contrasted. Available experimental evidence suggests that Ti incorporation increases net electron carrier concentrations in electrodes, most likely to the extent that (synthesis-dependent) charge compensating cation vacancies are not present. However, electron conductivity increases alone cannot quantitatively account for the large associated photoelectrochemical performance enhancements. The magnitudes of the effects of Ti incorporation on electronic and magnetic properties appear to be highly synthesis-dependent, which has made difficult the development of consistent and general mechanisms explaining experimental and theoretical observations. In this context, we consider how the electronic structure correlates with Ti impurity incorporation in alpha-Fe2O3 a from the perspective of synchrotron-based soft X-ray absorption spectroscopy measurements. Measurements are performed on sets of electrodes fabricated by five relevant and unrelated chemical and physical techniques. The effects of titanium impurities are reflected in the electronic structure through several universally observed spectral characteristics, irrespective of the synthesis techniques. Absorption spectra at the oxygen K-edge show that Ti incorporation is associated with new oxygen 2p-hybridized states, overlapping with and distorting the known unoccupied Fe 3d-O 2xp band of alpha-Fe2O3. This is an indication of mixing of Ti s and d states in the conduction band of alpha-Fe2O3. cc A comparison of spectra obtained with electron and photon detection shows that the effects of Ti incorporation on the conduction band are more pronounced in the near-surface region. Titanium L-2,L-3-edge absorption spectra show that titanium is incorporated into alpha-Fe2O3 as Ti4+ by all fabrication methods, with no long-range titania order detected. Iron L-2,L-3-edge absorption spectra indicate that Ti incorporation is not associated with the formation, of any significant concentrations of Fe2+, an observation common to many prior studies on this material system.
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| 10. |
- Sansone, Martina, et al.
(författare)
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Molecular characterization of a nosocomial outbreak of influenza B virus in an acute care hospital setting
- 2019
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Ingår i: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701. ; 101:1, s. 30-37
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To describe a hospital outbreak of influenza B virus (InfB) infection during season 2015/2016 by combining clinical and epidemiological data with molecular methods. Methods: Twenty patients diagnosed with InfB from a hospital outbreak over a four-week-period were included. Nasopharyngeal samples (NPS) positive for InfB by multiplex real-time polymerase chain reaction were sent for lineage typing and whole genome sequencing (WGS). Medical records were reviewed retrospectively for data regarding patient characteristics, localization, exposure and outcome, and assembled into a timeline. In order to find possible connections to the hospital outbreak, all patients with a positive NPS for influenza from the region over an extended time period were also reviewed. Findings: All 20 cases of InfB were of subtype B/Yamagata, and 17 of 20 patients could be linked to each other by either shared room or shared ward. WGS was successful or partially successful for 15 of the 17 viral isolates, and corroborated the epidemiological link supporting a close relationship. In the main affected ward, 19 of 75 inpatients were infected with InfB during the outbreak period, resulting in an attack rate of 25%. One probable case of influenza-related death was identified. Conclusion: InfB may spread within an acute care hospital, and advanced molecular methods may facilitate assessment of the source and extent of the outbreak. A multifaceted approach, including rapid diagnosis, early recognition of outbreak situations, simple rules for patient management and the use of regular infection control measures, may prevent nosocomial transmission of influenza virus. (C) 2018 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
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