| 1. |
- Alneberg, Johannes, et al.
(författare)
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BARM and BalticMicrobeDB, a reference metagenome and interface to meta-omic data for the Baltic Sea
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The Baltic Sea is one of the world’s largest brackish water bodies and is characterised by pronounced physicochemical gradients where microbes are the main biogeochemical catalysts. Meta-omic methods provide rich information on the composition of, and activities within microbial ecosystems, but are computationally heavy to perform. We here present the BAltic Sea Reference Metagenome (BARM), complete with annotated genes to facilitate further studies with much less computational effort. The assembly is constructed using 2.6 billion metagenomic reads from 81 water samples, spanning both spatial and temporal dimensions, and contains 6.8 million genes that have been annotated for function and taxonomy. The assembly is useful as a reference, facilitating taxonomic and functional annotation of additional samples by simply mapping their reads against the assembly. This capability is demonstrated by the successful mapping and annotation of 24 external samples. In addition, we present a public web interface, BalticMicrobeDB, for interactive exploratory analysis of the dataset.
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| 2. |
- Alneberg, Johannes, et al.
(författare)
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BARM and BalticMicrobeDB, a reference metagenome and interface to meta-omic data for the Baltic Sea
- 2018
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Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The Baltic Sea is one of the world's largest brackish water bodies and is characterised by pronounced physicochemical gradients where microbes are the main biogeochemical catalysts. Meta-omic methods provide rich information on the composition of, and activities within, microbial ecosystems, but are computationally heavy to perform. We here present the Baltic Sea Reference Metagenome (BARM), complete with annotated genes to facilitate further studies with much less computational effort. The assembly is constructed using 2.6 billion metagenomic reads from 81 water samples, spanning both spatial and temporal dimensions, and contains 6.8 million genes that have been annotated for function and taxonomy. The assembly is useful as a reference, facilitating taxonomic and functional annotation of additional samples by simply mapping their reads against the assembly. This capability is demonstrated by the successful mapping and annotation of 24 external samples. In addition, we present a public web interface, BalticMicrobeDB, for interactive exploratory analysis of the dataset. [GRAPHICS] .
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| 3. |
- Carlquist, Magnus, et al.
(författare)
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Physiological heterogeneities in microbial populations and implications for physical stress tolerance
- 2012
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Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Traditionally average values of the whole population are considered when analysing microbial cell cultivations. However, a typical microbial population in a bioreactor is heterogeneous in most phenotypes measurable at a single-cell level. There are indications that such heterogeneity may be unfavourable on the one hand (reduces yields and productivities), but also beneficial on the other hand (facilitates quick adaptation to new conditions - i.e. increases the robustness of the fermentation process). Understanding and control of microbial population heterogeneity is thus of major importance for improving microbial cell factory processes. Results: In this work, a dual reporter system was developed and applied to map growth and cell fitness heterogeneities within budding yeast populations during aerobic cultivation in well-mixed bioreactors. The reporter strain, which was based on the expression of green fluorescent protein (GFP) under the control of the ribosomal protein RPL22a promoter, made it possible to distinguish cell growth phases by the level of fluorescence intensity. Furthermore, by exploiting the strong correlation of intracellular GFP level and cell membrane integrity it was possible to distinguish subpopulations with high and low cell membrane robustness and hence ability to withstand freeze-thaw stress. A strong inverse correlation between growth and cell membrane robustness was observed, which further supports the hypothesis that cellular resources are limited and need to be distributed as a trade-off between two functions: growth and robustness. In addition, the trade-off was shown to vary within the population, and the occurrence of two distinct subpopulations shifting between these two antagonistic modes of cell operation could be distinguished. Conclusions: The reporter strain enabled mapping of population heterogeneities in growth and cell membrane robustness towards freeze-thaw stress at different phases of cell cultivation. The described reporter system is a valuable tool for understanding the effect of environmental conditions on population heterogeneity of microbial cells and thereby to understand cell responses during industrial process-like conditions. It may be applied to identify more robust subpopulations, and for developing novel strategies for strain improvement and process design for more effective bioprocessing.
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| 4. |
- Dossus, Laure, et al.
(författare)
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Hormonal, metabolic, and inflammatory profiles and endometrial cancer risk within the EPIC cohort--a factor analysis.
- 2013
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 177:8, s. 787-799
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Tidskriftsartikel (refereegranskat)abstract
- A "Western" lifestyle characterized by physical inactivity and excess weight is associated with a number of metabolic and hormonal dysregulations, including increased circulating estrogen levels, hyperinsulinemia, hyperglycemia, and chronic inflammation. The same hormonal and metabolic axes might mediate the association between this lifestyle and the development of endometrial cancer. Using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study carried out in 10 European countries during 1992-2000, we conducted a factor analysis to delineate important components that summarize the variation explained by a set of biomarkers and to examine their association with endometrial cancer risk. Prediagnostic levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, estrone, estradiol, C-peptide, insulin-like growth factor-binding proteins 1 and 2, adiponectin, high- and low-density lipoprotein cholesterol, glucose, triglycerides, tumor necrosis factor (TNF) α, soluble TNF receptors 1 and 2, C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist were measured in 233 incident endometrial cancer cases and 446 matched controls. Factor analysis identified 3 components associated with postmenopausal endometrial cancer risk that could be labeled "insulin resistance/metabolic syndrome," "steroids," and "inflammation" factors. A fourth component, "lipids," was not significantly associated with endometrial cancer. In conclusion, besides the well-known associations of risk with sex hormones and insulin-regulated physiological axes, our data further support the hypothesis that inflammation factors play a role in endometrial carcinogenesis.
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| 5. |
- Dossus, Laure, et al.
(författare)
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Obesity, inflammatory markers, and endometrial cancer risk : a prospective case-control study
- 2010
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 17:4, s. 1007-1019
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Tidskriftsartikel (refereegranskat)abstract
- Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case-control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values <0.05 were considered statistically significant. We observed a significant increase in risk of endometrial cancer with elevated levels of CRP (odds ratio (OR) for top versus bottom quartile: 1.58, 95% confidence interval (CI): 1.03-2.41, P(trend)=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08-2.54, P(trend)=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22-2.73, P(trend)=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10-20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu.
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| 6. |
- Dossus, Laure, et al.
(författare)
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Reproductive risk factors and endometrial cancer : the European prospective investigation into cancer and nutrition
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 127:2, s. 442-451
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Tidskriftsartikel (refereegranskat)abstract
- Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full-term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7-8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis.
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| 7. |
- Dossus, Laure, et al.
(författare)
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Tumor necrosis factor (TNF)-α, soluble TNF receptors and endometrial cancer risk : the EPIC study
- 2011
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Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 129:8, s. 2032-2037
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-α (TNF-α), one of the major pro-inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case-control study nested within the European prospective investigation into cancer and nutrition (EPIC) to examine the association of TNF-α and its two soluble receptors (sTNFR1 and sTNFR2) with endometrial cancer risk. Two-hundred-seventy cases and 518 matched controls were analyzed using conditional logistic regression. All statistical tests were two-sided. We observed an increased risk of endometrial cancer among women in the highest versus lowest quartile of TNF-α (odds ratio [OR]: 1.73, 95% CI: 1.09-2.73, Ptrend = 0.01), sTNFR1 (OR: 1.68, 95% CI: 0.99-2.86, Ptrend = 0.07) and sTNFR2 (OR: 1.53, 95%CI: 0.92-2.55, Ptrend = 0.03) after adjustment for body-mass-index, parity, age at menopause and previous postmenopausal hormone therapy use. Further adjustments for estrogens and C-peptide had minor effect on risk estimates. Our data show that elevated prediagnostic concentrations of TNF-α and its soluble receptors are related to a higher risk of endometrial cancer, particularly strong in women diagnosed within 2 years of blood donation. This is the first study of its kind and therefore deserves replication in further prospective studies.
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| 8. |
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| 9. |
- Fernandes, Rita Lencastre, et al.
(författare)
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Cell mass and cell cycle dynamics of an asynchronous budding yeast population: Experimental observations, flow cytometry data analysis, and multi-scale modeling
- 2013
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Ingår i: Biotechnology and Bioengineering. - : Wiley. - 1097-0290 .- 0006-3592. ; 110:3, s. 812-826
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Tidskriftsartikel (refereegranskat)abstract
- Despite traditionally regarded as identical, cells in a microbial cultivation present a distribution of phenotypic traits, forming a heterogeneous cell population. Moreover, the degree of heterogeneity is notably enhanced by changes in micro-environmental conditions. A major development in experimental single-cell studies has taken place in the last decades. It has however not been fully accompanied by similar contributions within data analysis and mathematical modeling. Indeed, literature reporting, for example, quantitative analyses of experimental single-cell observations and validation of model predictions for cell property distributions against experimental data is scarce. This study focuses on the experimental and mathematical description of the dynamics of cell size and cell cycle position distributions, of a population of Saccharomyces cerevisiae, in response to the substrate consumption observed during batch cultivation. The good agreement between the proposed multi-scale model (a population balance model [PBM] coupled to an unstructured model) and experimental data (both the overall physiology and cell size and cell cycle distributions) indicates that a mechanistic model is a suitable tool for describing the microbial population dynamics in a bioreactor. This study therefore contributes towards the understanding of the development of heterogeneous populations during microbial cultivations. More generally, it consists of a step towards a paradigm change in the study and description of cell cultivations, where average cell behaviors observed experimentally now are interpreted as a potential joint result of various co-existing single-cell behaviors, rather than a unique response common to all cells in the cultivation. Biotechnol. Bioeng. 2013; 110: 812826. (c) 2012 Wiley Periodicals, Inc.
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| 10. |
- Heins, Anna Lena, et al.
(författare)
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Quantitative flow cytometry to understand population heterogeneity in response to changes in substrate availability in escherichia coli and saccharomyces cerevisiae chemostats
- 2019
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 7:AUG
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Tidskriftsartikel (refereegranskat)abstract
- Microbial cells in bioprocesses are usually described with averaged parameters. But in fact, single cells within populations vary greatly in characteristics such as stress resistance, especially in response to carbon source gradients. Our aim was to introduce tools to quantify population heterogeneity in bioprocesses using a combination of reporter strains, flow cytometry, and easily comprehensible parameters. We calculated mean, mode, peak width, and coefficient of variance to describe distribution characteristics and temporal shifts in fluorescence intensity. The skewness and the slope of cumulative distribution function plots illustrated differences in distribution shape. These parameters are person-independent and precise. We demonstrated this by quantifying growth-related population heterogeneity of Saccharomyces cerevisiae and Escherichia coli reporter strains in steady-state of aerobic glucose-limited chemostat cultures at different dilution rates and in response to glucose pulses. Generally, slow-growing cells showed stronger responses to glucose excess than fast-growing cells. Cell robustness, measured as membrane integrity after exposure to freeze-thaw treatment, of fast-growing cells was strongly affected in subpopulations of low membrane robustness. Glucose pulses protected subpopulations of fast-growing but not slower-growing yeast cells against membrane damage. Our parameters could successfully describe population heterogeneity, thereby revealing physiological characteristics that might have been overlooked during traditional averaged analysis.
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| 11. |
- Hugerth, Luisa W., et al.
(författare)
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DegePrime, a Program for Degenerate Primer Design for Broad-Taxonomic-Range PCR in Microbial Ecology Studies
- 2014
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Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 80:16, s. 5116-5123
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Tidskriftsartikel (refereegranskat)abstract
- The taxonomic composition of a microbial community can be deduced by analyzing its rRNA gene content by, e. g., high-throughput DNA sequencing or DNA chips. Such methods typically are based on PCR amplification of rRNA gene sequences using broad-taxonomic-range PCR primers. In these analyses, the use of optimal primers is crucial for achieving an unbiased representation of community composition. Here, we present the computer program DegePrime that, for each position of a multiple sequence alignment, finds a degenerate oligomer of as high coverage as possible and outputs its coverage among taxonomic divisions. We show that our novel heuristic, which we call weighted randomized combination, performs better than previously described algorithms for solving the maximum coverage degenerate primer design problem. We previously used DegePrime to design a broad-taxonomic-range primer pair that targets the bacterial V3-V4 region (341F-805R) (D. P. Herlemann, M. Labrenz, K. Jurgens, S. Bertilsson, J. J. Waniek, and A. F. Andersson, ISME J. 5:1571-1579, 2011, http://dx.doi.org/10.1038/ismej.2011.41), and here we use the program to significantly increase the coverage of a primer pair (515F-806R) widely used for Illumina-based surveys of bacterial and archaeal diversity. By comparison with shotgun metagenomics, we show that the primers give an accurate representation of microbial diversity in natural samples.
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| 12. |
- Hugerth, Luisa W., et al.
(författare)
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Systematic Design of 18S rRNA Gene Primers for Determining Eukaryotic Diversity in Microbial Consortia
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4, s. 095567-
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Tidskriftsartikel (refereegranskat)abstract
- High-throughput sequencing of ribosomal RNA gene (rDNA) amplicons has opened up the door to large-scale comparative studies of microbial community structures. The short reads currently produced by massively parallel sequencing technologies make the choice of sequencing region crucial for accurate phylogenetic assignments. While for 16S rDNA, relevant regions have been well described, no truly systematic design of 18S rDNA primers aimed at resolving eukaryotic diversity has yet been reported. Here we used 31,862 18S rDNA sequences to design a set of broad-taxonomic range degenerate PCR primers. We simulated the phylogenetic information that each candidate primer pair would retrieve using paired-or single-end reads of various lengths, representing different sequencing technologies. Primer pairs targeting the V4 region performed best, allowing discrimination with paired-end reads as short as 150 bp (with 75% accuracy at genus level). The conditions for PCR amplification were optimised for one of these primer pairs and this was used to amplify 18S rDNA sequences from isolates as well as from a range of environmental samples which were then Illumina sequenced and analysed, revealing good concordance between expected and observed results. In summary, the reported primer sets will allow minimally biased assessment of eukaryotic diversity in different microbial ecosystems.
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| 13. |
- Jonsson, Hans, et al.
(författare)
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Genome sequence of segmented filamentous bacteria present in the human intestine
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Segmented filamentous bacteria (SFB) are unique immune modulatory bacteria colonizing the small intestine of a variety of animals in a host-specific manner. SFB exhibit filamentous growth and attach to the host's intestinal epithelium, offering a physical route of interaction. SFB affect functions of the host immune system, among them IgA production and T-cell maturation. Until now, no human-specific SFB genome has been reported. Here, we report the metagenomic reconstruction of an SFB genome from a human ileostomy sample. Phylogenomic analysis clusters the genome with SFB genomes from mouse, rat and turkey, but the genome is genetically distinct, displaying 65-71% average amino acid identity to the others. By screening human faecal metagenomic datasets, we identified individuals carrying sequences identical to the new SFB genome. We thus conclude that a unique SFB variant exists in humans and foresee a renewed interest in the elucidation of SFB functionality in this environment.
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| 14. |
- Lahmann, Petra H., et al.
(författare)
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Anthropometric measures and epithelial ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 126:10, s. 2404-2415
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Tidskriftsartikel (refereegranskat)abstract
- We examined the associations of measured anthropometric factors, including general and central adiposity and height, with ovarian cancer risk. We also investigated these associations by menopausal status and for specific histological subtypes. Among 226,798 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, there were 611 incident cases of primary, malignant, epithelial ovarian cancer diagnosed during a mean 8.9 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (as), adjusted for potential confounders. Compared to women with body mass index (BMI) < 25 kg/m(2), obesity (BMI >= 30 kg/m(2)) was associated with excess ovarian cancer risk for all women combined (HR = 1.33, 95% Cl = 1.05-1.68; p(trend) = 0.02) and postmenopausal women (HR = 1.59, 95% Cl = 1.20-2.10; p(trend) = 0.001), but the association was weaker for premenopausal women (HR = 1.16, 95% Cl = 0.65-2.06; p(trend) = 0.65). Neither height or weight gain, nor BMI-adjusted measures of fat distribution assessed by waist circumference, waist-hip ratio (WHR) or hip circumference were associated with overall risk. WHR was related to increased risk of mucinous tumors (BMI-adjusted HR per 0.05 unit increment = 1.17, 95% Cl = 1.00-1.38). For all women combined, no other significant associations with risk were observed for specific histological subtypes. This large, prospective study provides evidence that obesity is an important modifiable risk factor for epithelial ovarian cancer, particularly among postmenopausal women.
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| 15. |
- Lindh, Markus V., et al.
(författare)
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Disentangling seasonal bacterioplankton population dynamics by high-frequency sampling
- 2015
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Ingår i: Environmental Microbiology. - : Society for Applied Microbiology and John Wiley & Sons Ltd. - 1462-2912 .- 1462-2920. ; 17:7, s. 2459-2476
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Tidskriftsartikel (refereegranskat)abstract
- Multiyear comparisons of bacterioplankton succession reveal that environmental conditions drive community shifts with repeatable patterns between years. However, corresponding insight into bacterioplankton dynamics at a temporal resolution relevant for detailed examination of variation and characteristics of specific populations within years is essentially lacking. During 1 year, we collected 46 samples in the Baltic Sea for assessing bacterial community composition by 16S rRNA gene pyrosequencing (nearly twice weekly during productive season). Beta-diversity analysis showed distinct clustering of samples, attributable to seemingly synchronous temporal transitions among populations (populations defined by 97% 16S rRNA gene sequence identity). A wide spectrum of bacterioplankton dynamics was evident, where divergent temporal patterns resulted both from pronounced differences in relative abundance and presence/absence of populations. Rates of change in relative abundance calculated for individual populations ranged from 0.23 to 1.79 day(-1). Populations that were persistently dominant, transiently abundant or generally rare were found in several major bacterial groups, implying evolution has favoured a similar variety of life strategies within these groups. These findings suggest that high temporal resolution sampling allows constraining the timescales and frequencies at which distinct populations transition between being abundant or rare, thus potentially providing clues about physical, chemical or biological forcing on bacterioplankton community structure.
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| 16. |
- Lindh, Markus V., et al.
(författare)
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Metapopulation theory identifies biogeographical patterns among core and satellite marine bacteria scaling from tens to thousands of kilometers
- 2017
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Ingår i: Environmental Microbiology. - : Wiley-Blackwell. - 1462-2912 .- 1462-2920. ; 19:3, s. 1222-1236
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Tidskriftsartikel (refereegranskat)abstract
- Metapopulation theory developed in terrestrial ecology provides applicable frameworks for interpreting the role of local and regional processes in shaping species distribution patterns. Yet, empirical testing of metapopulation models on microbial communities is essentially lacking. We determined regional bacterioplankton dynamics from monthly transect sampling in the Baltic Sea Proper using 16S rRNA gene sequencing. A strong positive trend was found between local relative abundance and occupancy of populations. Notably, the occupancy-frequency distributions were significantly bimodal with a satellite mode of rare endemic populations and a core mode of abundant cosmopolitan populations (e.g. Synechococcus, SAR11 and SAR86 clade members). Temporal changes in population distributions supported several theoretical frameworks. Still, bimodality was found among bacterioplankton communities across the entire Baltic Sea, and was also frequent in globally distributed datasets. Datasets spanning waters with widely different physicochemical characteristics or environmental gradients typically lacked significant bimodal patterns. When such datasets were divided into subsets with coherent environmental conditions, bimodal patterns emerged, highlighting the importance of positive feedbacks between local abundance and occupancy within specific biomes. Thus, metapopulation theory applied to microbial biogeography can provide novel insights into the mechanisms governing shifts in biodiversity resulting from natural or anthropogenically induced changes in the environment.
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