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- Chamoun, Sherley, et al.
(author)
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Colistin Dependence in Extensively Drug-Resistant Acinetobacter baumannii Strain Is Associated with ISAjo2 and ISAba13 Insertions and Multiple Cellular Responses
- 2021
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In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:2
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Journal article (peer-reviewed)abstract
- The nosocomial opportunistic Gram-negative bacterial pathogen Acinetobacter baumannii is resistant to multiple antimicrobial agents and an emerging global health problem. The polymyxin antibiotic colistin, targeting the negatively charged lipid A component of the lipopolysaccharide on the bacterial cell surface, is often considered as the last-resort treatment, but resistance to colistin is unfortunately increasing worldwide. Notably, colistin-susceptible A. baumannii can also develop a colistin dependence after exposure to this drug in vitro. Colistin dependence might represent a stepping stone to resistance also in vivo. However, the mechanisms are far from clear. To address this issue, we combined proteogenomics, high-resolution microscopy, and lipid profiling to characterize and compare A. baumannii colistin-susceptible clinical isolate (Ab-S) of to its colistin-dependent subpopulation (Ab-D) obtained after subsequent passages in moderate colistin concentrations. Incidentally, in the colistin-dependent subpopulation the lpxA gene was disrupted by insertion of ISAjo2, the lipid A biosynthesis terminated, and Ab-D cells displayed a lipooligosaccharide (LOS)-deficient phenotype. Moreover, both mlaD and pldA genes were perturbed by insertions of ISAjo2 and ISAba13, and LOS-deficient bacteria displayed a capsule with decreased thickness as well as other surface imperfections. The major changes in relative protein abundance levels were detected in type 6 secretion system (T6SS) components, the resistance-nodulation-division (RND)-type efflux pumps, and in proteins involved in maintenance of outer membrane asymmetry. These findings suggest that colistin dependence in A. baumannii involves an ensemble of mechanisms seen in resistance development and accompanied by complex cellular events related to insertional sequences (ISs)-triggered LOS-deficiency. To our knowledge, this is the first study demonstrating the involvement of ISAjo2 and ISAba13 IS elements in the modulation of the lipid A biosynthesis and associated development of dependence on colistin.
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| 2. |
- Maeso-Alonso, Laura, et al.
(author)
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p73 is required for vessel integrity controlling endothelial junctional dynamics through Angiomotin
- 2022
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In: Cellular and Molecular Life Sciences (CMLS). - : Springer Nature. - 1420-682X .- 1420-9071. ; 79:10
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Journal article (peer-reviewed)abstract
- Preservation of blood vessel integrity, which is critical for normal physiology and organ function, is controlled at multiple levels, including endothelial junctions. However, the mechanism that controls the adequate assembly of endothelial cell junctions is not fully defined. Here, we uncover TAp73 transcription factor as a vascular architect that orchestrates transcriptional programs involved in cell junction establishment and developmental blood vessel morphogenesis and identify Angiomotin (AMOT) as a TAp73 direct transcriptional target. Knockdown of p73 in endothelial cells not only results in decreased Angiomotin expression and localization at intercellular junctions, but also affects its downstream function regarding Yes-associated protein (YAP) cytoplasmic sequestration upon cell-cell contact. Analysis of adherens junctional morphology after p73-knockdown in human endothelial cells revealed striking alterations, particularly a sharp increase in serrated junctions and actin bundles appearing as stress fibers, both features associated with enhanced barrier permeability. In turn, stabilization of Angiomotin levels rescued those junctional defects, confirming that TAp73 controls endothelial junction dynamics, at least in part, through the regulation of Angiomotin. The observed defects in monolayer integrity were linked to hyperpermeability and reduced transendothelial electric resistance. Moreover, p73-knockout retinas showed a defective sprout morphology coupled with hemorrhages, highlighting the physiological relevance of p73 regulation in the maintenance of vessel integrity in vivo. We propose a new model in which TAp73 acts as a vascular architect integrating transcriptional programs that will impinge with Angiomotin/YAP signaling to maintain junctional dynamics and integrity, while balancing endothelial cell rearrangements in angiogenic vessels.
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| 3. |
- Schmidt, Linnéa, et al.
(author)
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Case-specific potentiation of glioblastoma drugs by pterostilbene
- 2016
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:45, s. 73200-73215
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Journal article (peer-reviewed)abstract
- Glioblastoma multiforme (GBM, astrocytoma grade IV) is the most common malignant primary brain tumor in adults. Addressing the shortage of effective treatment options for this cancer, we explored repurposing of existing drugs into combinations with potent activity against GBM cells. We report that the phytoalexin pterostilbene is a potentiator of two drugs with previously reported anti-GBM activity, the EGFR inhibitor gefitinib and the antidepressant sertraline. Combinations of either of these two compounds with pterostilbene suppress cell growth, viability, sphere formation and inhibit migration in tumor GBM cell (GC) cultures. The potentiating effect of pterostilbene was observed to a varying degree across a panel of 41 patient-derived GCs, and correlated in a case specific manner with the presence of missense mutation of EGFR and PIK3CA and a focal deletion of the chromosomal region 1p32. We identify pterostilbene-induced cell cycle arrest, synergistic inhibition of MAPK activity and induction of Thioredoxin interacting protein (TXNIP) as possible mechanisms behind pterostilbene's effect. Our results highlight a nontoxic stilbenoid compound as a modulator of anticancer drug response, and indicate that pterostilbene might be used to modulate two anticancer compounds in well-defined sets of GBM patients.
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| 5. |
- Bastardo Zambrano, Luis Alejandro, et al.
(author)
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Soluble complexes in aqueous mixtures of low charge density comb polyelectrolyte and oppositely charged surfactant probed by scattering and NMR
- 2007
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In: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 312, s. 21-33
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Journal article (peer-reviewed)abstract
- A low charge density polyelectrolyte with a high graft density of 45 units long poly(ethylene oxide) side-chains has been synthesized. In this comb polymer, denoted PEO45 MEMA:METAC-2, 2 mol% of the repeating methacrylate units in the polymer backbone carry a permanent positive charge and the remaining 98 mol% a 45 unit long PEO side-chain. Here we describe the solution conformation of this polymer and its association with an anionic surfactant, sodium dodecylsulfate, SDS. It will be shown that the polymer can be viewed as a stiff rod with a cross-section radius of gyration of 29 Å. The cross section of the rod contracts with increasing temperature due to decreased solvency of the PEO side-chains. The anionic surfactant associates to a significant degree with PEO45 MEMA:METAC-2 to form soluble complexes at all stoichiometries. A cooperative association is observed as the free SDS concentration approaches 7 mM. At saturation the number of SDS molecules associated with the polymer amounts to 10 for each PEO side-chain. Two distinct populations of associated surfactants are observed, one is suggested to be molecularly distributed over the comb polymer and the other constitutes small micellar-like structures at the periphery of the aggregate. These conclusions are reached based on results from small-angle neutron scattering, static light scattering, NMR, and surface tension measurements.
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| 6. |
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| 7. |
- Claesson, Anna Maria
(author)
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Kinesernas vänner : en analys av missionens berättelse som ideologi och utopi
- 2001
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Doctoral thesis (other academic/artistic)abstract
- This thesis intends to answer the question: How was the narrative of the mission in China formulated and used to engender and sustain the fervour of the friends of the mission in the 1890s? It was at this time, with growing unemployment, lack of housing, and of poverty – a time when new and challenging ideas emerge – that the interest in the missions to China awoke. The context of the missionary narrative in this thesis is the Swedish town of Jönköping, a place with a strong religious image and therefore often called “Småland’s Jerusalem”. How did a group of young men – members of the YMCA – shape and develop their thoughts in this troublesome time? In the self-contained manner of thought of the missionary movement's collective mind, the fervour and devotion was built upon the members' sense of belonging together, of everybody participating in the missionary work, and in the conviction of its feasibility and ultimate success. But the story sent home by the missionary was more complex and it may appear contradictory and difficult to interpret. With the help of four “figures of thought” – the concept was developed by the sociologist Johan Asplund – I have been able, however, to discover a pattern. Sometimes the narrative expressed the trusting hope of universalism and metamorphosis, sometimes Christian self-assurance and righteousness, sometimes the utopian Apocalypse. Thus the social imagination of the missionary movement – my arguments about the social imagination and its ideological and utopian functions derive from the philosopher Paul Ricoeur – created a communal structure of belonging and participation, and legitimised a sense of confirmation and selection. In this structure dwelled the fervour of the missionary movement. Here, an imperfect world and a complex narrative were held together, and within this structure one's own life became purposeful and valuable. But the social imagination also contains true utopian functions in Riceour's sense. The social imagination's utopian function of exploration, criticism and alternative solutions was for instance used by female missionaries (and, to be true, some male) to tear down the barriers between the sexes, but also by uneducated young men (and young women) to overcome barriers of class and education. Both groups challenged the regular social order, which in the 1890s was already reeling. The figure of thought’s universal view of humanity gave them the right, the possible metamorphosis the ability, and the Christian standard the confirmation of truth. With the help of the utopian promise, zealous workers were created willing to give the missionary cause their body and soul. The apocalyptic figure of thought, and a conviction of belonging to the Chosen, legitimised the leap, for some even made it necessary. Finally, the thesis discusses the importance and consequences of the fervour in one town, Jönköping. For many of pious in Jönköping, the missions were a journey towards a single, common world.
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| 8. |
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| 9. |
- Claesson, Ann, et al.
(author)
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Taluppfattning i brus vid användning av öppet anpassade hörapparater med och utan riktmikrofon och bullerreducering
- 2012
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Other publication (other academic/artistic)abstract
- Syftet med studien var att undersöka hur hörapparater med öppen anpassning påverkar taluppfattning i brus vid användande av rundupptagande mikrofon, riktmikrofon respektive riktmikrofon i kombination med brusreducering samt att jämföra med en tät insats som referens. Utförande Deltagarna fick provat ut bakom-örat-hörapparater med öppen anpassning bilateralt med tre olika program: 1) rundupptagande mikrofon 2) riktmikrofon 3) riktmikrofon kombinerat med brusreducering. Taluppfattningströskel i brus med Hagermans meningar mättes med de tre olika programmen och även utan hörapparat. Som referens gjordes även samma mätningar med en tät insats. Talet presenterades rakt framifrån på en fast nivå, 65 dB SPL. Ett brus som innehåller samma frekvensspektrum som talet presenterades från fyra högtalare. Bruset ändrades adaptivt baserat på hur många rätt personen återgav. Deltagare I denna studie deltog 20 personer som hade en lätt till måttlig hörselnedsättning och ingen tidigare erfarenhet av hörapparater. Resultat Resultaten visade en signifikant förbättring med riktmikrofon och riktmikrofon kombinerat med brusreducering jämfört med rundupptagande mikrofon. Däremot fick vi ingen signifikant skillnad mellan riktmikrofon och riktmikrofon kombinerat med brusreducering. Det blev heller ingen signifikant skillnad mellan rundupptagande mikrofon och utan hörapparat. Konklusioner Slutsatsen av detta är att personer med lätt till måttlig hörselnedsättning har hjälp av öppet anpassade hörapparater med riktmikrofon, men däremot får de ingen förbättring med rundupptagande mikrofon i en sorlig miljö.
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| 10. |
- Claesson, Ing-Marie, et al.
(author)
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Pregnant womens intention to breastfeed; their estimated extent and duration of the forthcoming breastfeeding in relation to the actual breastfeeding in the first year postpartum-A Swedish cohort study
- 2019
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In: Midwifery. - : ELSEVIER SCI LTD. - 0266-6138 .- 1532-3099. ; 76, s. 102-109
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Journal article (peer-reviewed)abstract
- Objectives: To investigate the prenatal intention to breastfeed and the estimated extent and duration of the forthcoming breastfeeding among nulliparous and multiparous women in different Body Mass Index (BMI) classes. Furthermore, in a sub-group we study the actual breastfeeding in relation to the prenatal intended extent and duration. Design: A prospective cohort study. Methods: A total of 775 pregnant women answered a questionnaire concerning their intention to breastfeed and how they estimated the extent and duration of the forthcoming breastfeeding. In a sub-group of 174 women, data from the actual breastfeeding were obtained. Findings: There was no difference concerning intention to breastfeed among underweight and normal weight women, overweight or obese nulliparous or multiparous women. Fewer multiparous women with BMI amp;lt;25 judged that the forthcoming breastfeeding would be partial, compared to multiparous women with overweight and obesity (p = 0.003). Furthermore, there was a significant difference within the group of nulliparous women concerning the prenatal intended extent and the actual breastfeeding at two weeks and five months postnatally (p = 0.000 and p = 0.041). There were more underweight and normal weight and overweight women who breastfed exclusively two weeks postnatally, compared with obese women. Additional, at five months postnatally there were more obese women who had ceased to breastfeed, than underweight and normal weight women. Conclusions: Among pregnant multiparous women there were more overweight and obese women who judged that the forthcoming breastfeeding would be partial, than pregnant underweight and normal weight women. The prenatal estimated extent of the forthcoming breastfeeding differed from the actually extent of breastfeeding among nulliparous women. Implications for practice: The antenatal breastfeeding information and education should be tailored to prepare every woman/couple, irrespective of maternal body composition for the forthcoming task and furthermore, the continuum of care, from antenatal care to Child Health Service should offer a supportive atmosphere to protect and promote breastfeeding (C) 2019 Elsevier Ltd. All rights reserved.
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