| 1. |
- Wahlgren, Weixiao Yuan, 1970, et al.
(författare)
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Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new Na+ site.
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Many pathogenic bacteria utilise sialic acids as an energy source or use them as an external coating to evade immune detection. As such, bacteria that colonise sialylated environments deploy specific transporters to mediate import of scavenged sialic acids. Here, we report a substrate-bound 1.95Å resolution structure and subsequent characterisation of SiaT, a sialic acid transporter from Proteus mirabilis. SiaT is a secondary active transporter of the sodium solute symporter (SSS) family, which use Na+ gradients to drive the uptake of extracellular substrates. SiaT adopts the LeuT-fold and is in an outward-open conformation in complex with the sialic acid N-acetylneuraminic acid and two Na+ ions. One Na+ binds to the conserved Na2 site, while the second Na+ binds to a new position, termed Na3, which is conserved in many SSS family members. Functional and molecular dynamics studies validate the substrate-binding site and demonstrate that both Na+ sites regulate N-acetylneuraminic acid transport.
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| 2. |
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| 3. |
- Ancillotti, Mirko, 1981-, et al.
(författare)
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The Status Quo Problem and the Role of Consumers Against Antimicrobial Resistance
- 2022
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Ingår i: Frontiers in Sustainable Food Systems. - : Frontiers Media S.A.. - 2571-581X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance occurs when microorganisms survive exposure and proliferate in the presence of therapeutic levels of antimicrobial drugs. Because antimicrobial resistance is increasing, it is vital to encourage consumers to change and adopt smarter antibiotic behaviour. Despite World Health Organization's efforts to combat antibiotic resistance and their emphasis on the importance of public involvement, the role of consumers has been overlooked. The manifold responsibility for antibiotic resistance extends across different actors, including food retailers and consumers. Given this shared responsibility, a blame game arises and no action occurs. To overcome this status quo situation, we draw attention to the potential role of individual responsibility and social pressure to encourage consumers to adopt smart antibiotic behaviour but also to empower them. Conditions must be put in place to enable consumers' critical evaluation of the health-related and ethical aspects of their food choices. Such behaviour can be facilitated using digital innovations to support informed choices, in store and online.
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| 4. |
- Baladi, Tom, 1991, et al.
(författare)
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Stealth Fluorescence Labeling for Live Microscopy Imaging of mRNA Delivery
- 2021
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 143:14, s. 5413-5424
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Tidskriftsartikel (refereegranskat)abstract
- Methods for tracking RNA inside living cells without perturbing their natural interactions and functions are critical within biology and, in particular, to facilitate studies of therapeutic RNA delivery. We present a stealth labeling approach that can efficiently, and with high fidelity, generate RNA transcripts, through enzymatic incorporation of the triphosphate of tCO, a fluorescent tricyclic cytosine analogue. We demonstrate this by incorporation of tCO in up to 100% of the natural cytosine positions of a 1.2 kb mRNA encoding for the histone H2B fused to GFP (H2B:GFP). Spectroscopic characterization of this mRNA shows that the incorporation rate of tCO is similar to cytosine, which allows for efficient labeling and controlled tuning of labeling ratios for different applications. Using live cell confocal microscopy and flow cytometry, we show that the tCO-labeled mRNA is efficiently translated into H2B:GFP inside human cells. Hence, we not only develop the use of fluorescent base analogue labeling of nucleic acids in live-cell microscopy but also, importantly, show that the resulting transcript is translated into the correct protein. Moreover, the spectral properties of our transcripts and their translation product allow for their straightforward, simultaneous visualization in live cells. Finally, we find that chemically transfected tCO-labeled RNA, unlike a state-of-the-art fluorescently labeled RNA, gives rise to expression of a similar amount of protein as its natural counterpart, hence representing a methodology for studying natural, unperturbed processing of mRNA used in RNA therapeutics and in vaccines, like the ones developed against SARS-CoV-2.
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| 5. |
- Ballantyne, David, et al.
(författare)
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All that is solid melts into air : the servicescape in digital service space
- 2017
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Ingår i: Journal of Services Marketing. - : Emerald Group Publishing Limited. - 0887-6045. ; 31:3, s. 226-235
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Tidskriftsartikel (refereegranskat)abstract
- Purpose - The emergence of new social media is shifting the market place for business towards virtual market space. In the light of the emerging digital space for new forms of marketing, the traditional servicescape concept is critically examined. This paper aims to show why servicescape concepts and attitudes need to be adapted for digital media. Design/methodology/approach - First, the authors explain how the traditional servicescape concept adds meaning to a service provider's value-proposition by modifying customer expectations and customer experience. Second, recognising that the environment for service is no longer bound to a physical place, the authors discuss the implications of the epistemic shift involved. Findings - The authors' examination shows that digital service space challenges traditional concepts about what constitutes a customer experience and derived value. The authors conceptually "zoom out" into a virtual service eco-system and show with exemplar examples why the servicescape in digital space is more socially embedded and necessarily more fluid in its time-space design. In the more advanced sites, interactions between various artificial bodies (avatars) are co-created by controlling off-line participant-actors; yet, these participant-actors remain strangers to each other at an off-line level. This is entirely a new and radical development of old times. Research limitations/implications - The research findings are based on scholarly research of the relevant literature, from practitioner reports, and evidence emerging from the examination of many digital web-sites. It has not been the authors' intention to objectively represent current servicescape functionalities but more to indicate the major directions of change with exemplar examples. The future cannot be predicted, but their interpretive conclusions suggest major challenges in service marketing and management logic ahead. New forms of digital servicescape are still being created as technology and service imagination enables, so further research interest in virtual atmospherics can be expected. Practical implications - Social media platforms are enabling organisations to learn more about their customers and also to engage them more. In these changing times, bricks and mortar stores would be well advised to review their servicescape presence to allow and encourage engagement with the more involved consumers. And, by integrating their digital space into their physical place, bricks and mortar stores might take on more relationship oriented processlike characteristics, both in the digital space and in their physical places, with developments on one platform leading to possible service innovations on the other. Social implications - The digital era is changing consumer behaviour. Service managers need to take into account that many customers are already equally as engaged with digital-space social networks as they once were with bricks and mortar stores. The more time consumers as participant-actors spend in social networks, the decision on what and where to buy is decided by interactions with friends and other influencers. Originality/value - New forms of digital servicescape are being created as technology and service imagination enables. Further scholarly research interest in virtual atmospherics can be expected, impacting on the authors' sense of place, and self-identity.
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| 6. |
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| 7. |
- Bergman, Mats, 1964-, et al.
(författare)
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Handeln i svåra tider
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Gracias, J., et al.
(författare)
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Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia risk has been associated with the complement component 4 (C4) genes. Here the authors show that C4A is elevated in individuals with schizophrenia. Postsynaptic density is reduced in schizophrenia, and risk variants increasing complement component 4A (C4A) gene expression are linked to excessive synapse elimination. In two independent cohorts, we show that cerebrospinal fluid (CSF) C4A concentration is elevated in patients with first-episode psychosis (FEP) who develop schizophrenia (FEP-SCZ: median 0.41 fmol/ul [CI = 0.34-0.45], FEP-non-SCZ: median 0.29 fmol/ul [CI = 0.22-0.35], healthy controls: median 0.28 [CI = 0.24-0.33]). We show that the CSF elevation of C4A in FEP-SCZ exceeds what can be expected from genetic risk variance in the C4 locus, and in patient-derived cellular models we identify a mechanism dependent on the disease-associated cytokines interleukin (IL)-1beta and IL-6 to selectively increase neuronal C4A mRNA expression. In patient-derived CSF, we confirm that IL-1beta correlates with C4A controlled for genetically predicted C4A RNA expression (r = 0.39; CI: 0.01-0.68). These results suggest a role of C4A in early schizophrenia pathophysiology.
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| 9. |
- Gustavsson, Tobias, et al.
(författare)
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Long-term effects of immunotherapy with a brain penetrating Aβ antibody in a mouse model of Alzheimer's disease
- 2023
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central (BMC). - 1758-9193. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBrain-directed immunotherapy is a promising strategy to target amyloid-β (Aβ) deposits in Alzheimer’s disease (AD). In the present study, we compared the therapeutic efficacy of the Aβ protofibril targeting antibody RmAb158 with its bispecific variant RmAb158-scFv8D3, which enters the brain by transferrin receptor-mediated transcytosis.MethodsAppNL−G−F knock-in mice received RmAb158, RmAb158-scFv8D3, or PBS in three treatment regimens. First, to assess the acute therapeutic effect, a single antibody dose was given to 5 months old AppNL−G−F mice, with evaluation after 3 days. Second, to assess the antibodies’ ability to halt the progression of Aβ pathology, 3 months old AppNL−G−F mice received three doses during a week, with evaluation after 2 months. Reduction of RmAb158-scFv8D3 immunogenicity was explored by introducing mutations in the antibody or by depletion of CD4+ T cells. Third, to study the effects of chronic treatment, 7-month-old AppNL−G−F mice were CD4+ T cell depleted and treated with weekly antibody injections for 8 weeks, including a final diagnostic dose of [125I]RmAb158-scFv8D3, to determine its brain uptake ex vivo. Soluble Aβ aggregates and total Aβ42 were quantified with ELISA and immunostaining.ResultsNeither RmAb158-scFv8D3 nor RmAb158 reduced soluble Aβ protofibrils or insoluble Aβ1-42 after a single injection treatment. After three successive injections, Aβ1-42 was reduced in mice treated with RmAb158, with a similar trend in RmAb158-scFv8D3-treated mice. Bispecific antibody immunogenicity was somewhat reduced by directed mutations, but CD4+ T cell depletion was used for long-term therapy. CD4+ T cell-depleted mice, chronically treated with RmAb158-scFv8D3, showed a dose-dependent increase in blood concentration of the diagnostic [125I]RmAb158-scFv8D3, while concentration was low in plasma and brain. Chronic treatment did not affect soluble Aβ aggregates, but a reduction in total Aβ42 was seen in the cortex of mice treated with both antibodies.ConclusionsBoth RmAb158 and its bispecific variant RmAb158-scFv8D3 achieved positive effects of long-term treatment. Despite its ability to efficiently enter the brain, the benefit of using the bispecific antibody in chronic treatment was limited by its reduced plasma exposure, which may be a result of interactions with TfR or the immune system. Future research will focus in new antibody formats to further improve Aβ immunotherapy.
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| 10. |
- Hall, Per, 1954, et al.
(författare)
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Influence of Natural Oxygenation of Baltic Proper Deep Water on Benthic Recycling and Removal of Phosphorus, Nitrogen, Silicon and Carbon
- 2017
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- At the end of 2014, a major Baltic inflow (MBI) brought oxygenated, salty water into the Baltic proper and reached the long-term anoxic Eastern Gotland Basin (EGB) by March 2015. In July 2015, we measured benthic fluxes of phosphorus (P), nitrogen (N) and silicon (Si) nutrients and dissolved inorganic carbon (DIC) in situ using an autonomous benthic lander at deep sites (170-210 m) in the EGB, where the bottom water oxygen concentration was 30-45 µM. The same in situ methodology was used to measure benthic fluxes at the same sites in 2008-2010, but then under anoxic conditions. The high efflux of phosphate under anoxic conditions became lower upon oxygenation, and turned into an influx in about 50 % of the flux measurements. The C:P and N:P ratios of the benthic solute flux changed from clearly below the Redfield ratio (on average about 70 and 3-4, respectively) under anoxia to approaching or being well above the Redfield ratio upon oxygenation. These observations demonstrate retention of P in newly oxygenated sediments. We found no significant effect of oxygenation on the benthic ammonium, silicate and DIC flux. We also measured benthic denitrification, anammox and dissimilatory nitrate reduction to ammonium (DNRA) rates at the same sites using isotope-pairing techniques. The bottom water of the long-term anoxic EGB contained less than 0.5 µM nitrate in 2008-2010, but the oxygenation event created bottom water nitrate concentrations of about 10 µM in July 2015 and the benthic flux of nitrate was consistently directed into the sediment. Nitrate reduction to both dinitrogen gas (denitrification) and ammonium (DNRA) was initiated in the newly oxygenated sediments, while anammox activity was negligible. We estimated the influence of this oxygenation event on the magnitudes of the integrated benthic P flux (the internal P load) and the fixed N removal through benthic and pelagic denitrification by comparing with a hypothetical scenario without the MBI. Our calculations suggest that the oxygenation triggered by the MBI in July 2015, extrapolated to the basin-wide scale of the Baltic proper, decreased the internal P load by 23% and increased the total (benthic plus pelagic) denitrification by 18%.
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