| 1. |
- Canals, Rocio, et al.
(författare)
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Adding function to the genome of African Salmonella Typhimurium ST313 strain D23580
- 2019
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Ingår i: PLoS biology. - : PUBLIC LIBRARY SCIENCE. - 1544-9173 .- 1545-7885. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Salmonella Typhimurium sequence type (ST) 313 causes invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa, targeting susceptible HIV+, malarial, or malnourished individuals. An in-depth genomic comparison between the ST313 isolate D23580 and the well-characterized ST19 isolate 4/74 that causes gastroenteritis across the globe revealed extensive synteny. To understand how the 856 nucleotide variations generated phenotypic differences, we devised a large-scale experimental approach that involved the global gene expression analysis of strains D23580 and 4/74 grown in 16 infection-relevant growth conditions. Comparison of transcriptional patterns identified virulence and metabolic genes that were differentially expressed between D23580 versus 4/74, many of which were validated by proteomics. We also uncovered the S. Typhimurium D23580 and 4/74 genes that showed expression differences during infection of murine macrophages. Our comparative transcriptomic data are presented in a new enhanced version of the Salmonella expression compendium, SalComD23580: http://bioinf.gen.tcd.ie/cgi-bin/salcom_v2.pl. We discovered that the ablation of melibiose utilization was caused by three independent SNP mutations in D23580 that are shared across ST313 lineage 2, suggesting that the ability to catabolize this carbon source has been negatively selected during ST313 evolution. The data revealed a novel, to our knowledge, plasmid maintenance system involving a plasmid-encoded CysS cysteinyl-tRNA synthetase, highlighting the power of large-scale comparative multicondition analyses to pinpoint key phenotypic differences between bacterial pathovariants.
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| 2. |
- Carlsson, Emilia, 1983, et al.
(författare)
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Child-health nurses' experiences from using pictorial support with families within child-health services in Sweden
- 2024
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Ingår i: ACTA PAEDIATRICA. - 0803-5253 .- 1651-2227.
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Tidskriftsartikel (refereegranskat)abstract
- AimTo gain insight into child-health nurses' experiences of using pictorial support in health visits within child-health services.MethodsA qualitative study involving interviews conducted with 17 child-health nurses in Sweden. The interview data were analysed using content analysis.ResultsThe nurses experienced that pictorial support could facilitate communication with families and increase opportunities for children to participate in child-health services, although it may come with challenges. This theme can be broken down into three main categories: (1) Pictorial support makes interaction with families clearer and easier and is used in different ways; (2) The design and extensiveness of the pictorial support can create obstacles; and (3) Pictorial support influences children's attitudes towards, and participation in, health visits.ConclusionPictorial support is an important and useful tool in child-health nurses' own work and improves their communication with children and caregivers during health visits. It can also increase children's participation and help them express themselves. Communicative tools such as pictorial support are very helpful to healthcare professionals striving to offer child- and family-centred care.
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| 3. |
- Ghosh, Anirban, et al.
(författare)
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Contact-dependent growth inhibition induces high levels of antibiotic-tolerant persister cells in clonal bacterial populations
- 2018
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Ingår i: EMBO Journal. - : WILEY. - 0261-4189 .- 1460-2075. ; 37:9
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial populations can use bet-hedging strategies to cope with rapidly changing environments. One example is non-growing cells in clonal bacterial populations that are able to persist antibiotic treatment. Previous studies suggest that persisters arise in bacterial populations either stochastically through variation in levels of global signalling molecules between individual cells, or in response to various stresses. Here, we show that toxins used in contact-dependent growth inhibition (CDI) create persisters upon direct contact with cells lacking sufficient levels of CdiI immunity protein, which would otherwise bind to and neutralize toxin activity. CDI-mediated persisters form through a feedforward cycle where the toxic activity of the CdiA toxin increases cellular (p)ppGpp levels, which results in Lon-mediated degradation of the immunity protein and more free toxin. Thus, CDI systems mediate a population density-dependent bet-hedging strategy, where the fraction of non-growing cells is increased only when there are many cells of the same genotype. This may be one of the mechanisms of how CDI systems increase the fitness of their hosts.
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| 4. |
- Hässler, Signe, et al.
(författare)
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Aire deficient mice develop hematopoetic irregularities and marginal zone B cell lymphoma
- 2006
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 108:6, s. 1941-1948
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type I (APS I) is an inherited recessive disorder with a progressive immunological destruction of many tissues including the adrenal cortex, the parathyroid glands, and the gonads. APS I is caused by mutations in the AIRE gene (autoimmune regulator), expressed in cells of the thymus and spleen, suggesting a role in central and peripheral tolerance. Aire(-/-) mice replicate the autoimmune features of APS I patients with the presence of multiple autoantibodies and lymphocytic infiltrates in various tissues, but young mice appear clinically healthy. We here report the investigation of 15- to 24-month-old Aire(-/-) mice. We did not observe any endocrinological abnormalities, nor did sera from these mice recognize known APS I autoantigens. Interestingly, however, there was a high frequency of marginal zone B-cell lymphoma in Aire(-/-) mice and liver infiltrates of B cells, suggesting chronic antigen exposure and exaggerated activation. Furthermore, increased numbers of monocytes in blood were identified as well as augmented numbers of metallophilic macrophages in the spleen. We propose that Aire, in addition to its function in the thymus, also has a peripheral regulatory role by controlling the development of antigen-presenting cells (APCs) and marginal zone B-cell activation.
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| 5. |
- Larsson Hammarlöf, Disa, et al.
(författare)
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Turnover of mRNAs is one of the essential functions of RNase E
- 2015
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Ingår i: Molecular Microbiology. - : Wiley. - 0950-382X .- 1365-2958. ; 98:1, s. 34-45
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Tidskriftsartikel (refereegranskat)abstract
- RNase E is an essential bacterial endoribonuclease with a central role in processing tRNAs and rRNA, and turning over mRNAs. Previous studies in strains carrying mutations in the rne structural gene have shown that tRNA processing is likely to be an essential function of RNase E but have not determined whether mRNA turnover is also an essential function. To address this we selected extragenic suppressors of temperature-sensitive mutations in rne that cause a large increase in mRNA half-life at the non-permissive temperature. Fifteen suppressors were mapped to three different loci: relBE (toxin-antitoxin system); vacB (RNase R); and rpsA (ribosomal protein S1). Each suppressor class has the potential to interact with mRNA and each restores wild-type levels of mRNA turnover but does not reverse the minor defects in tRNA and rRNA processing. RelE toxin is especially interesting because its only known activity is to cleave mRNAs in the ribosomal A-site. The relBE suppressor mutations increase transcription of relE, and controlled overexpression of RelE alone was sufficient to suppress the rne ts phenotype. Suppression increased turnover of some major mRNAs (tufA, ompA) but not all mRNAs. We propose that turnover of some mRNAs is one of the essential functions of RNase E.
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| 6. |
- Mannergren Selimovic, Johanna, et al.
(författare)
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Gender andTransition in Libya : Mapping women’s participation in post-conflict reconstruction
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- More than three years after the end of the Gaddafi regime, Libya is struggling to end a vicious circle of violence in order to take steps towards reconciliation and durable peace. This paper analyses the ongoing transitional period in Libya from a gender perspective. It maps the most pressing concerns of the post-conflict transition: women’s lack of security in both public and private spaces, the silence around conflict-related sexual violence in transitional justice processes, the struggles for political representation and gender-sensitive electoral processes, the challenges of including both men and women in reconciliation efforts, and the lack of sustained international engagement for gender justice in Libya. It is argued that women’s security concerns remain unaddressed, and that formal and informal structures interact to exclude women from decision-making and transitional justice processes. At the same time the study shows that women in Libya take an active role in the political transformation and have made some inroads into traditionally male domains of politics.
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| 7. |
- Powers, TuShun R., et al.
(författare)
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Intracellular niche-specific profiling reveals transcriptional adaptations required for the cytosolic lifestyle of Salmonella enterica
- 2021
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 17:8, s. e1009280-
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Tidskriftsartikel (refereegranskat)abstract
- Salmonella enterica serovar Typhimurium (S. Typhimurium) is a zoonotic pathogen that causes diarrheal disease in humans and animals. During salmonellosis, S. Typhimurium colonizes epithelial cells lining the gastrointestinal tract. S. Typhimurium has an unusual lifestyle in epithelial cells that begins within an endocytic-derived Salmonella-containing vacuole (SCV), followed by escape into the cytosol, epithelial cell lysis and bacterial release. The cytosol is a more permissive environment than the SCV and supports rapid bacterial growth. The physicochemical conditions encountered by S. Typhimurium within the epithelial cytosol, and the bacterial genes required for cytosolic colonization, remain largely unknown. Here we have exploited the parallel colonization strategies of S. Typhimurium in epithelial cells to decipher the two niche-specific bacterial virulence programs. By combining a population-based RNA-seq approach with single-cell microscopic analysis, we identified bacterial genes with cytosol-induced or vacuole-induced expression signatures. Using these genes as environmental biosensors, we defined that Salmonella is exposed to oxidative stress and iron and manganese deprivation in the cytosol and zinc and magnesium deprivation in the SCV. Furthermore, iron availability was critical for optimal S. Typhimurium replication in the cytosol, as well as entC, fepB, soxS, mntH and sitA. Virulence genes that are typically associated with extracellular bacteria, namely Salmonella pathogenicity island 1 (SPI1) and SPI4, showed increased expression in the cytosol compared to vacuole. Our study reveals that the cytosolic and vacuolar S. Typhimurium virulence gene programs are unique to, and tailored for, residence within distinct intracellular compartments. This archetypical vacuole-adapted pathogen therefore requires extensive transcriptional reprogramming to successfully colonize the mammalian cytosol.
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