| 1. |
- Alneberg, Johannes, et al.
(författare)
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Ecosystem-wide metagenomic binning enables prediction of ecological niches from genomes
- 2020
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Ingår i: Communications Biology. - : Nature Publishing Group. - 2399-3642. ; 3:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Alneberg et al. conduct metagenomics binning of water samples collected over major environmental gradients in the Baltic Sea. They use machine-learning to predict the placement of genome clusters along niche gradients based on the content of functional genes. The genome encodes the metabolic and functional capabilities of an organism and should be a major determinant of its ecological niche. Yet, it is unknown if the niche can be predicted directly from the genome. Here, we conduct metagenomic binning on 123 water samples spanning major environmental gradients of the Baltic Sea. The resulting 1961 metagenome-assembled genomes represent 352 species-level clusters that correspond to 1/3 of the metagenome sequences of the prokaryotic size-fraction. By using machine-learning, the placement of a genome cluster along various niche gradients (salinity level, depth, size-fraction) could be predicted based solely on its functional genes. The same approach predicted the genomes' placement in a virtual niche-space that captures the highest variation in distribution patterns. The predictions generally outperformed those inferred from phylogenetic information. Our study demonstrates a strong link between genome and ecological niche and provides a conceptual framework for predictive ecology based on genomic data.
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| 2. |
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| 3. |
- Andersson, Gerhard, et al.
(författare)
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Chronic Pain in Older Adults: A Controlled Pilot Trial of a Brief Cognitive-Behavioural Group Treatment
- 2012
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Ingår i: Behavioural and Cognitive Psychotherapy. - : Cambridge University Press (CUP). - 1352-4658 .- 1469-1833. ; 40:2, s. 239-244
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic pain is a common condition among older adults. While cognitive behaviour therapy (CBT) has been tested in numerous studies on adults and children there are fewer studies on older persons. The objective of this study was to investigate the effects of a six-session CBT group treatment for older persons with chronic pain. As a secondary aim we investigated whether treatment credibility was associated with outcome. Method: We included 21 persons (mean age = 72.0 years) who were randomly allocated to either a waitlist condition or treatment consisting of applied relaxation, with the addition of problem solving, assertiveness, communication strategies, sleep management, and relapse prevention. Results: Few statistically significant effects were found on measures of pain, mood, anxiety, and quality of life; however, a significant treatment effect with a between group effect size of d = 1.0 was observed with respect to perceived ability to function despite the discomfort of pain. Conclusion: The study provides some preliminary support for the use of group-based CBT with a focus on applied relaxation for older adults with chronic pain.
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| 4. |
- Andersson, Karin, 1972, et al.
(författare)
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Survivin controls biogenesis of microRNA in smokers: A link to pathogenesis of rheumatoid arthritis.
- 2017
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Ingår i: Biochimica et biophysica acta. - : Elsevier BV. - 0006-3002. ; 1863:3, s. 663-673
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRs) represent a part of epigenetic control of autoimmunity gaining increasing attention in rheumatoid arthritis (RA). Since cigarette smoking plays important role in RA pathogenesis and reprograms transcriptional profile of miRNAs, we ask if the onco-protein survivin, a novel biomarker of RA, may provide a link between smoking and miRNA. Studying survivin expression in leukocytes of 144 female RA patients we observed that smoking patients had higher survivin transcription and a remarkable spreading of survivin isoforms. This was associated with restricted pattern and low production of miRs. Additionally, miRNA processing enzymes Dicer and DGRC8 were decreased in the patients with survivin isoform spreading. The direct contribution of survivin in miRs biogenesis was confirmed by a massive increase of miRs production following inhibition of survivin in leukocyte cultures. Dicer is shown to mediate these effects of survivin. Chromatin immunoprecipitation analysis demonstrated binding of survivin to the Dicer promoter region. Dicer expression increased 5-folds following survivin inhibition. Taken together, this study presents experimental evidence of a novel cellular function of survivin, control of miRs biogenesis. Up-regulation of survivin in smokers suggests its role as effector of the adverse epigenetic control in RA.
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| 5. |
- Barnes, Brian R, et al.
(författare)
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The 5'-AMP-activated protein kinase gamma3 isoform has a key role in carbohydrate and lipid metabolism in glycolytic skeletal muscle
- 2004
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 279:37, s. 38441-38447
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Tidskriftsartikel (refereegranskat)abstract
- 5'-AMP-activated protein kinase (AMPK) is a metabolic stress sensor present in all eukaryotes. A dominant missense mutation (R225Q) in pig PRKAG3, encoding the muscle-specific gamma3 isoform, causes a marked increase in glycogen content. To determine the functional role of the AMPK gamma3 isoform, we generated transgenic mice with skeletal muscle-specific expression of wild type or mutant (225Q) mouse gamma3 as well as Prkag3 knockout mice. Glycogen resynthesis after exercise was impaired in AMPK gamma3 knock-out mice and markedly enhanced in transgenic mutant mice. An AMPK activator failed to increase skeletal muscle glucose uptake in AMPK gamma3 knock-out mice, whereas contraction effects were preserved. When placed on a high fat diet, transgenic mutant mice but not knock-out mice were protected against excessive triglyceride accumulation and insulin resistance in skeletal muscle. Transfection experiments reveal the R225Q mutation is associated with higher basal AMPK activity and diminished AMP dependence. Our results validate the muscle-specific AMPK gamma3 isoform as a therapeutic target for prevention and treatment of insulin resistance.
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| 6. |
- Dahlström, Lisen Arnheim, et al.
(författare)
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Prospective seroepidemiologic study of human papillomavirus and other risk factors in cervical cancer
- 2011
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 20:12, s. 2541-2550
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several sexually transmitted infections (STI) have been reported to interact with human papillomavirus (HPV) in the etiology of cervical cancer. A large cohort study is required to obtain a both unbiased and stable estimate of their effects. Methods: Four major biobanks in the Nordic Countries containing samples from about 1,000,000 subjects were linked with nation-wide cancer registries. Serum samples from 604 women with invasive cervical cancer (ICC) diagnosed on average 10 years after sampling and 2,980 matched control women were retrieved and analyzed with serology for key STI. Results: Exposure to HPV16 was the strongest risk factor for cervical cancer [ OR = 2.4; 95% confidence interval (CI), 2.0-3.0], particularly for squamous cell carcinoma (OR = 2.9; 95% CI, 2.2-3.7). HPV18 was strongly associated with increased risk for adenocarcinoma (OR = 2.3; 95% CI, 1.3-4.1). Baseline seropositivity for HPV16 did not confer any increased risk for HPV18 DNA-positive cancer and conversely HPV18 seropositivity had no association with HPV16 DNA-positive cancers. HPV6 had no effect on its own (OR = 1.1; 95% CI, 0.9-1.3), but had an antagonistic effect on the risk conferred by HPV16 (P < 0.01). Herpes simplex virus 2 had little or no association (OR = 1.1; 95% CI, 0.8-1.4). Previous exposure to Chlamydia trachomatis, as indicated by serum antibodies, had a strongly increased risk for cervical cancer (OR = 1.9; 95% CI, 1.5-2.3). Conclusions: A large prospective study has assessed the role of different STIs in cervical cancer. Impact: Prospective evidence supports cofactor role of some STI in cervical cancer. Cancer Epidemiol Biomarkers Prev; 20(12); 2541-50. (C) 2011 AACR.
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| 7. |
- Dillner, Joakim, et al.
(författare)
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Antibodies to SARS-CoV-2 and risk of past or future sick leave
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The extent that antibodies to SARS-CoV-2 may protect against future virus-associated disease is unknown. We invited all employees (n=15,300) at work at the Karolinska University Hospital, Stockholm, Sweden to participate in a study examining SARS-Cov-2 antibodies in relation to registered sick leave. For consenting 12,928 healthy hospital employees antibodies to SARS-CoV-2 could be determined and compared to participant sick leave records. Subjects with viral serum antibodies were not at excess risk for future sick leave (adjusted odds ratio (OR) controlling for age and sex: 0.85 [95% confidence interval (CI) (0.85 (0.43-1.68)]. By contrast, subjects with antibodies had an excess risk for sick leave in the weeks prior to testing [adjusted OR in multivariate analysis: 3.34 (2.98-3.74)]. Thus, presence of viral antibodies marks past disease and protection against excess risk of future disease. Knowledge of whether exposed subjects have had disease in the past or are at risk for future disease is essential for planning of control measures.Trial registration: First registered on 02/06/20, ClinicalTrials.gov NCT04411576.
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| 8. |
- Eriksson, Kaja, et al.
(författare)
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Salivary Microbiota and Host-Inflammatory Responses in Periodontitis Affected Individuals With and Without Rheumatoid Arthritis
- 2022
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Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesPeriodontitis and rheumatoid arthritis (RA) are two widespread chronic inflammatory diseases with a previously suggested association. The objective of the current study was to compare the oral microbial composition and host ' s inflammatory mediator profile of saliva samples obtained from subjects with periodontitis, with and without RA, as well as to predict biomarkers, of bacterial pathogens and/or inflammatory mediators, for classification of samples associated with periodontitis and RA. MethodsSalivary samples were obtained from 53 patients with periodontitis and RA and 48 non-RA with chronic periodontitis. The microbial composition was identified using 16S rRNA gene sequencing and compared across periodontitis patients with and without RA. Levels of inflammatory mediators were determined using a multiplex bead assay, compared between the groups and correlated to the microbial profile. The achieved data was analysed using PCoA, DESeq2 and two machine learning algorithms, OPLS-DA and sPLS-DA. ResultsDifferential abundance DESeq2 analyses showed that the four most highly enriched (log2 FC >20) amplicon sequence variants (ASVs) in the non-RA periodontitis group included Alloprevotella sp., Prevotella sp., Haemophilus sp., and Actinomyces sp. whereas Granulicatella sp., Veillonella sp., Megasphaera sp., and Fusobacterium nucleatum were the most highly enriched ASVs (log2 FC >20) in the RA group. OPLS-DA with log2 FC analyses demonstrated that the top ASVs with the highest importance included Vampirovibrio sp. having a positive correlation with non-RA group, and seven ASVs belonging to Sphingomonas insulae, Sphingobium sp., Novosphingobium aromaticivorans, Delftia acidovorans, Aquabacterium spp. and Sphingomonas echinoides with a positive correlation with RA group. Among the detected inflammatory mediators in saliva samples, TWEAK/TNFSF12, IL-35, IFN-alpha 2, pentraxin-3, gp130/sIL6Rb, sIL-6Ra, IL-19 and sTNF-R1 were found to be significantly increased in patients with periodontitis and RA compared to non-RA group with periodontitis. Moreover, correlations between ASVs and inflammatory mediators using sPLS-DA analysis revealed that TWEAK/TNFSF12, pentraxin-3 and IL-19 were positively correlated with the ASVs Sphingobium sp., Acidovorax delafieldii, Novosphingobium sp., and Aquabacterium sp. ConclusionOur results suggest that the combination of microbes and host inflammatory mediators could be more efficient to be used as a predictable biomarker associated with periodontitis and RA, as compared to microbes and inflammatory mediators alone.
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| 9. |
- Gustafsson, Nina M. S., et al.
(författare)
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Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The glycolytic PFKFB3 enzyme is widely overexpressed in cancer cells and an emerging anticancer target. Here, we identify PFKFB3 as a critical factor in homologous recombination (HR) repair of DNA double-strand breaks. PFKFB3 rapidly relocates into ionizing radiation (IR)-induced nuclear foci in an MRN-ATM-gamma H2AX-MDC1-dependent manner and co-localizes with DNA damage and HR repair proteins. PFKFB3 relocalization is critical for recruitment of HR proteins, HR activity, and cell survival upon IR. We develop KAN0438757, a small molecule inhibitor that potently targets PFKFB3. Pharmacological PFKFB3 inhibition impairs recruitment of ribonucleotide reductase M2 and deoxynucleotide incorporation upon DNA repair, and reduces dNTP levels. Importantly, KAN0438757 induces radiosensitization in transformed cells while leaving non-transformed cells unaffected. In summary, we identify a key role for PFKFB3 enzymatic activity in HR repair and present KAN0438757, a selective PFKFB3 inhibitor that could potentially be used as a strategy for the treatment of cancer.
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| 10. |
- Hedman, Erik, et al.
(författare)
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Internet-delivered exposure-based cognitive-behavioural therapy and behavioural stress management for severe health anxiety : randomised controlled trial
- 2014
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 205:4, s. 307-314
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Tidskriftsartikel (refereegranskat)abstract
- Background Exposure-based cognitive-behavioural therapy (CBT) delivered via the internet has been shown to be effective for severe health anxiety (hypochondriasis) but has not been compared with an active, effective and credible psychological treatment, such as behavioural stress management (BSM). Aims To investigate two internet-delivered treatments - exposure-based CBT v. BSM - for severe health anxiety in a randomised controlled trial (trial registration: NCT01673035). Method Participants (n = 158) with a principal diagnosis of severe health anxiety were allocated to 12 weeks of exposure-based CBT (n = 79) or BSM (n = 79) delivered via the internet. The Health Anxiety Inventory (HAI) was the primary outcome. Results Internet-delivered exposure-based CBT led to a significantly greater improvement on the HAI compared with BSM. However, both treatment groups made large improvements on the HAI (pre-to-post-treatment Cohen's d: exposure-based CBT, 1.78; BSM, 1.22). Conclusions Exposure-based CBT delivered via the internet is an efficacious treatment for severe health anxiety.
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