| 51. |
- Strandberg, Gabriel, et al.
(författare)
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Prompt Thrombo-Inflammatory Response to Ischemia-Reperfusion Injury and Kidney Transplant Outcomes
- 2023
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Ingår i: KIDNEY INTERNATIONAL REPORTS. - : Elsevier. - 2468-0249. ; 8:12, s. 2592-2602
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In kidney transplantation (KT), the role of the intravascular innate immune system (IIIS) in response to ischemia-reperfusion injury (IRI) is not well-understood. Here, we studied parallel changes in the generation of key activation products of the proteolytic cascade systems of the IIIS following living donor (LD) and deceased donor (DD) transplantation and evaluated potential associations with clinical outcomes.Methods: In a cohort study, 63 patients undergoing LD (n = 26) and DD (n = 37) transplantation were prospectively included. Fifteen DD kidneys were preserved with hypothermic machine perfusion (HMP), and the remaining were cold stored. Activation products of the kallikrein-kinin, coagulation, and complement systems were measured in blood samples obtained systemically at baseline and locally from the transplant renal vein at 1, 10, and 30 minutes after reperfusion.Results: DD kidneys exhibited a prompt and interlinked activation of all 3 cascade systems of IIIS post-reperfusion, indicating a robust and local thrombo-inflammatory response to IRI. In this initial response, the complement activation product sC5b-9 exhibited a robust correlation with other IIIS activation markers and displayed a strong association with short-term and mid-term (24-month) graft dysfunction. In contrast, LD kidneys did not exhibit this thrombo-inflammatory response. The use of HMP was associated with reduced thromboinflammation and preserved mid-term kidney function.Conclusion: Kidneys from DD are vulnerable to a prompt thrombo-inflammatory response to IRI, which adversely affects both short-term and long-term allograft function. Strategies aimed at minimizing graft immunogenicity prior to reperfusion are crucial to mitigate the intricate inflammatory response to IRI.
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| 52. |
- Tampere, M, et al.
(författare)
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Novel Broad-Spectrum Antiviral Inhibitors Targeting Host Factors Essential for Replication of Pathogenic RNA Viruses
- 2020
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Recent RNA virus outbreaks such as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ebola virus (EBOV) have caused worldwide health emergencies highlighting the urgent need for new antiviral strategies. Targeting host cell pathways supporting viral replication is an attractive approach for development of antiviral compounds, especially with new, unexplored viruses where knowledge of virus biology is limited. Here, we present a strategy to identify host-targeted small molecule inhibitors using an image-based phenotypic antiviral screening assay followed by extensive target identification efforts revealing altered cellular pathways upon antiviral compound treatment. The newly discovered antiviral compounds showed broad-range antiviral activity against pathogenic RNA viruses such as SARS-CoV-2, EBOV and Crimean-Congo hemorrhagic fever virus (CCHFV). Target identification of the antiviral compounds by thermal protein profiling revealed major effects on proteostasis pathways and disturbance in interactions between cellular HSP70 complex and viral proteins, illustrating the supportive role of HSP70 on many RNA viruses across virus families. Collectively, this strategy identifies new small molecule inhibitors with broad antiviral activity against pathogenic RNA viruses, but also uncovers novel virus biology urgently needed for design of new antiviral therapies.
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| 53. |
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| 54. |
- Alhamdow, Ayman, et al.
(författare)
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Low-level exposure to polycyclic aromatic hydrocarbons is associated with reduced lung function among Swedish young adults
- 2021
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 197
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to adverse pulmonary effects. However, the impact of low-level environmental PAH exposure on lung function in early adulthood remains uncertain. Objectives: To evaluate the associations between urinary PAH metabolites and lung function parameters in young adults. Methods: Urinary metabolites of pyrene, phenanthrene, and fluorene were analysed in 1000 young adults from Sweden (age 22–25 years) using LC-MS/MS. Lung function and eosinophilic airway inflammation were measured by spirometry and exhaled nitric oxide fraction (FeNO), respectively. Linear regression analysis was used to evaluate associations between PAH metabolites and the outcomes. Results: Median urinary concentrations of 1-OH-pyrene, ∑OH-phenanthrene, and ∑OH-fluorene were 0.066, 0.36, 0.22 μg/L, respectively. We found inverse associations of ∑OH-phenanthrene and ∑OH-fluorene with FEV1 and FVC, as well as between 1-OH-pyrene and FEV1/FVC ratio (adjusted P < 0.05; all participants). An increase of 1% in ∑OH-fluorene was associated with a decrease of 73 mL in FEV1 and 59 mL in FVC. In addition, ∑OH-phenanthrene concentrations were, in a dose-response manner, inversely associated with FEV1 (B from −109 to −48 compared with the lowest quartile of ∑OH-phenanthrene; p trend 0.004) and FVC (B from −159 to −102 compared with lowest quartile; p-trend <0.001). Similar dose-response associations were also observed between ∑OH-fluorene and FEV1 and FVC, as well as between 1-OH-pyrene and FEV1/FVC (p-trend <0.05). There was no association between PAH exposure and FeNO, nor was there an interaction with smoking, sex, or asthma. Conclusion: Low-level PAH exposure was, in a dose-response manner, associated with reduced lung function in young adults. Our findings have public health implications due to i) the widespread occurrence of PAHs in the environment and ii) the clinical relevance of lung function in predicting all-cause and cardiovascular disease mortality.
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| 55. |
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| 56. |
- Andersson, Björn, et al.
(författare)
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Strain-specific metabarcoding reveals rapid evolution of copper tolerance in populations of the coastal diatom Skeletonema marinoi
- 2023
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Ingår i: Molecular Ecology. - 0962-1083 .- 1365-294X.
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Tidskriftsartikel (refereegranskat)abstract
- Phytoplankton have short generation times, flexible reproduction strategies, large population sizes and high standing genetic diversity, traits that should facilitate rapid evolution under directional selection. We quantified local adaptation of copper tolerance in a population of the diatom Skeletonema marinoi from a mining-exposed inlet in the Baltic Sea and in a non-exposed population 100 km away. We hypothesized that mining pollution has driven evolution of elevated copper tolerance in the impacted population of S. marinoi. Assays of 58 strains originating from sediment resting stages revealed no difference in the average tolerance to copper between the two populations. However, variation within populations was greater at the mining site, with three strains displaying hyper-tolerant phenotypes. In an artificial evolution experiment, we used a novel intraspecific metabarcoding locus to track selection and quantify fitness of all 58 strains during co-cultivation in one control and one toxic copper treatment. As expected, the hyper-tolerant strains enabled rapid evolution of copper tolerance in the mining-exposed population through selection on available strain diversity. Within 42 days, in each experimental replicate a single strain dominated (30%–99% abundance) but different strains dominated the different treatments. The reference population developed tolerance beyond expectations primarily due to slowly developing plastic response in one strain, suggesting that different modes of copper tolerance are present in the two populations. Our findings provide novel empirical evidence that standing genetic diversity of phytoplankton resting stage allows populations to evolve rapidly (20–50 generations) and flexibly on timescales relevant for seasonal bloom progressions.
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| 57. |
- Bekkin, Renat, 1978-
(författare)
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People of reliable loyalty… : Muftiates and the State in Modern Russia
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation presents a full-fledged portrait of the muftiate (spiritual administration of Muslims) in modern Russia. Designed initially for the purpose of controlling religious activity, over time the institution of the muftiate was appropriated by Muslims and became a key factor in preserving national identity for different ethnic groups of Tatars. In modern Russia numerous muftiates play the controversial role of administrative bodies responsible for the enforcement of some aspects of domestic and foreign policy on behalf of the state.Bekkin’s research focuses on muftiates in the European part of Russia, examining both their historical development and their functioning in the modern context. The analysis draws on academic literature, written and oral texts produced by the ministers of the Islamic religion, and archival sources, as well as numerous interviews with current and former muftis and other Islamic bureaucrats. Following Douglass North’s theory of institutions, the author distinguishes between the muftiate as an institution and the muftiate as a religious organization. In the first case the muftiate encompasses a set of rules (restrictions) that are both formal (reflected in the laws, charters of spiritual administrations of Muslims) and informal (not reflected in the legislation). Individual Islamic religious organizations (muftiates in a narrow sense) function according to these rules. By analyzing both the formal and informal precepts which regulate the status and the activity of spiritual administrations of Muslims in the Russian Empire and the Soviet Union, and continue to do so in modern Russia, the author makes an attempt to explain the viability of the institution of the muftiate.Basing himself in the theory of the economics of religion, the author treats Russian muftiates as firms competing in the Islamic segment of the religious market. He applies economic principles in analyzing how the muftiates interact with each other, with other religious organizations in Russia, and with the Russian state. The author provides his own classification of muftiates in Russia, depending on the role they play in the religious market.
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| 58. |
- Berglund, Anders, 1974-, et al.
(författare)
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An Assessment Review of Learning Performance when adopting Augmented Reality in Engineering Education
- 2022
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Ingår i: Bidrag från 8:e Utvecklingskonferensen för Sveriges ingenjörsutbildningar. - 9789178672714 ; , s. 32-35
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Konferensbidrag (refereegranskat)abstract
- Augmented Reality (AR) has developed rapidly inrecent years and it is about to become a mainstream technology.We are witnessing how emerging technologies such as AR has been introduced and today widely applied in engineering education.The turmoil caused by the COVID-19 pandemic has in many ways highlighted the importance of AR technology for collaboration and remote assistance of frontline workers. Enabling experts to be much more productive in helping to debug problems and resolve production issues remotely. This kind of hands-on support and tutoring opportunities play well into the possibilities embedded in a more digitalized approach to engineering education. Still, both industries and universities are exploring ways to enhance the value-added credentials that come along with an integration and investment of AR. This paper set out to understand what type of assessment that are used to drive learning performance amongstudents in engineering education.
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| 59. |
- Berglund, A., et al.
(författare)
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Through the eyes of a research team : Using theory to enhance STEM Education
- 2021
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Ingår i: 6th International STEM Education Conference, iSTEM-Ed 2021. - : Institute of Electrical and Electronics Engineers Inc..
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Konferensbidrag (refereegranskat)abstract
- Computing Education Research (CER) is an example of Discipline-Based Education Research (DBER) that has developed substantively over the last few decades. This is especially true for the Uppsala Computing Education Research Group (UpCERG). In this paper, we use UpCERG as a lens to see how a conscious use of theory can enhance the quality of STEM education. This is accomplished through presenting our use of the concept 'theory' in the paper and by using the theses produced by the group as a way to illustrate the increased importance of theoretical development.
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| 60. |
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