| 1. |
- Ameur, Adam, et al.
(författare)
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SweGen : a whole-genome data resource of genetic variability in a cross-section of the Swedish population
- 2017
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Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 25:11, s. 1253-1260
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.
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| 2. |
- Adamsson, Jenni, 1977, et al.
(författare)
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Gastric expression of IL-17A and IFNγ in Helicobacter pylori infected individuals is related to symptoms
- 2017
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Ingår i: Cytokine. - : Elsevier BV. - 1043-4666. ; 99, s. 30-34
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic infection with Helicobacter pylori leads to gastritis and in a subpopulation of infected individuals to ulcers and cancer. Bacterial virulence factors and host immune inflammatory responses are risk factors related to disease. CD4+ T cells secrete cytokines that promote inflammation and an anti-bacterial response in the gastric mucosa during infection. The aim of the study was to investigate the pattern of expression of CD4+ T cell derived cytokines, IL-17A and IFNγ in paired antrum and corpus biopsies and correlate it to H. pylori infection outcome. Methods: Gene and protein expression of IL-17A and IFNγ was analyzed in gastric biopsies from H. pylori infected subjects with non-ulcer dyspepsia (NUD) or gastric ulcer; and for comparison uninfected individuals. Results: Upregulation of IL-17A and IFNγ gene expression was seen in corpus and antrum biopsies of H. pylori infected individuals with NUD compared to in uninfected controls. The expression of these cytokines correlated significantly with each other. Immunofluorescence staining revealed increased frequencies of IL-17A+ and IFNγ+ cells in antrum biopsies of gastric ulcer patients compared to of H. pylori infected NUD individuals; positive cells were not detected in any of the biopsies of uninfected controls. The frequencies of IFNγ and IL-17A+ cells correlated positively with inflammation in the antrum, but not the corpus, of H. pylori infected individuals. In the antrum, while there was no significant evidence of correlation between IFNγ and bacterial score, a positive correlation between bacterial score and IL-17A+ cells was seen. Conclusions: In H. pylori infected individuals, the frequencies of IFNγ and IL-17A+ cells were increased in the antrum, particularly in patients with H. pylori induced gastric ulcers. Even though H. pylori colonized both the corpus and antrum regions of the stomach, the cytokine responses and subsequent pathology were mainly detected in the antrum. © 2017 Elsevier Ltd
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| 3. |
- Fauville, Geraldine, et al.
(författare)
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Can Facebook be used to increase scientific literacy? A case study of the Monterey Bay Aquarium Research Institute Facebook page and ocean literacy
- 2015
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Ingår i: Computers and education. - : Elsevier BV. - 0360-1315. ; 82, s. 60-73
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Tidskriftsartikel (refereegranskat)abstract
- The Internet provides a unique opportunity for scientists to be in direct contact with the public in order to promote citizens' scientific literacy. Recently, Internet users have started to spend most of their online time on social networking sites (SNS). Knowledge of how these SNSs work as an arena for interaction, as well as for the development of scientific literacy, is important to guide scientists' activities online, and to be able to understand how people develop knowledge of science. This was evaluated by scrutinizing the Facebook page of the Monterey Bay Aquarium Research Institute and the consequences for users' ocean literacy. We investigated which practices could increase the number of users reached by a Facebook story. We also found that Facebook pages do not offer the appropriate social context to foster participation since it has only a few of the features of an arena where such practices could develop.
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| 4. |
- Jonna, Venkateswara Rao, et al.
(författare)
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Diversity in Overall Activity Regulation of Ribonucleotide Reductase
- 2015
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; , s. 1-24
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Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotide reductase (RNR) catalyzes the reduction of ribonucleotides to the corresponding deoxyribonucleotides, which are used as building blocks for DNA replication and repair. This process is tightly regulated via two allosteric sites, the specificity site (s-site) and the overall activity site (a-site). The a-site resides in an N-terminal ATP cone domain that binds dATP or ATP and functions as an on/off switch, whereas the composite s-site binds ATP, dATP, dTTP, or dGTP and determines which substrate to reduce. There are three classes of RNRs, and class I RNRs consist of different combinations of α and β subunits. In eukaryotic and Escherichia coli canonical class I RNRs, dATP inhibits enzyme activity through the formation of inactive α6 and α4β4 complexes, respectively. Here we show that the Pseudomonas aeruginosa class I RNR has a duplicated ATP cone domain and represents a third mechanism of overall activity regulation. Each α polypeptide binds three dATP molecules, and the N-terminal ATP cone is critical for binding two of the dATPs because a truncated protein lacking this cone could only bind one dATP to its s-site. ATP activates the enzyme solely by preventing dATP from binding. The dATP-induced inactive form is an α4 complex, which can interact with β2 to form a non-productive α4β2 complex. Other allosteric effectors induce a mixture of α2 and α4 forms, with the former being able to interact with β2 to form active α2β2 complexes. The unique features of the P. aeruginosa RNR are interesting both from evolutionary and drug discovery perspectives.
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| 5. |
- Kindlund, Bert, 1969, et al.
(författare)
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CD4(+) regulatory T cells in gastric cancer mucosa are proliferating and express high levels of IL-10 but little TGF-β.
- 2017
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Ingår i: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. - : Springer Science and Business Media LLC. - 1436-3291 .- 1436-3305. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- An increase of regulatory T cells, defined as CD25(high)- and/or FOXP3(+)-expressing CD4(+) T cells, within tumors has been reported in several studies. Tregs promote tumor growth by modulating the antitumor immune response, mainly through inhibition of T-cell-mediated tumor cell killing: this has been suggested to be dependent on IL-10 and/or TGF-β. In stomach cancer, the mechanisms behind the accumulation of Tregs in tumor tissue has not been fully elucidated, and neither has Treg gene expression in situ.
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| 6. |
- Thorell, Kaisa, 1983, et al.
(författare)
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Identification of a Latin American-specific BabA adhesin variant through whole genome sequencing of Helicobacter pylori patient isolates from Nicaragua
- 2016
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Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Helicobacter pylori (H. pylori) is one of the most common bacterial infections in humans and this infection can lead to gastric ulcers and gastric cancer. H. pylori is one of the most genetically variable human pathogens and the ability of the bacterium to bind to the host epithelium as well as the presence of different virulence factors and genetic variants within these genes have been associated with disease severity. Nicaragua has particularly high gastric cancer incidence and we therefore studied Nicaraguan clinical H. pylori isolates for factors that could contribute to cancer risk. Methods: The complete genomes of fifty-two Nicaraguan H. pylori isolates were sequenced and assembled de novo, and phylogenetic and virulence factor analyses were performed. Results: The Nicaraguan isolates showed phylogenetic relationship with West African isolates in whole-genome sequence comparisons and with Western and urban South-and Central American isolates using MLSA (Multi-locus sequence analysis). A majority, 77 % of the isolates carried the cancer-associated virulence gene cagA and also the s1/i1/m1 vacuolating cytotoxin, vacA allele combination, which is linked to increased severity of disease. Specifically, we also found that Nicaraguan isolates have a blood group-binding adhesin (BabA) variant highly similar to previously reported BabA sequences from Latin America, including from isolates belonging to other phylogenetic groups. These BabA sequences were found to be under positive selection at several amino acid positions that differed from the global collection of isolates. Conclusion: The discovery of a Latin American BabA variant, independent of overall phylogenetic background, suggests hitherto unknown host or environmental factors within the Latin American population giving H. pylori isolates carrying this adhesin variant a selective advantage, which could affect pathogenesis and risk for sequelae through specific adherence properties.
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| 7. |
- Thorell, Kaisa, 1983, et al.
(författare)
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In vivo analysis of the viable microbiota and Helicobacter pylori transcriptome in gastric infection and early stages of carcinogenesis
- 2017
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Ingår i: Infection and Immunity. - 1098-5522 .- 0019-9567. ; 85:10
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence shows that the human microbiota plays a larger role in disease progression and health than previously anticipated. Helicobacter pylori, the causative agent of gastric cancer and duodenal and gastric ulcers, was early associated with gastric disease, but it has also been proposed that the accompanying microbiota in Helicobacter pylori-infected individuals might affect disease progression and gastric cancer development. In this study, the composition of the transcriptionally active microbial community and H. pylori gene expression were determined using metatranscriptomic RNA sequencing of stomach biopsy specimens from individuals with different H. pylori infection statuses and premalignant tissue changes. The results show that H. pylori completely dominates the microbiota not only in infected individuals but also in most individuals classified as H. pylori uninfected using conventional methods. Furthermore, H. pylori abundance is positively correlated with the presence of Campylobacter, Deinococcus, and Sulfurospirillum. Finally, we quantified the expression of a large number of Helicobacter pylori genes and found high expression of genes involved in pH regulation and nickel transport. Our study is the first to dissect the viable microbiota of the human stomach by metatranscriptomic analysis, and it shows that metatranscriptomic analysis of the gastric microbiota is feasible and can provide new insights into how bacteria respond in vivo to variations in the stomach microenvironment and at different stages of disease progression.
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