| 1. |
- FitzGerald, L. M., et al.
(författare)
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Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality : an analysis of 12,082 prostate cancer cases
- 2018
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 21:2, s. 228-237
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Tidskriftsartikel (refereegranskat)abstract
- Background Prostate cancer (PCa) is a leading cause of mortality and genetic factors can influence tumour aggressiveness. Several germline variants have been associated with PCa-specific mortality (PCSM), but further replication evidence is needed. Methods Twenty-two previously identified PCSM-associated genetic variants were genotyped in seven PCa cohorts (12,082 patients; 1544 PCa deaths). For each cohort, Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for risk of PCSM associated with each variant. Data were then combined using a meta-analysis approach. Results Fifteen SNPs were associated with PCSM in at least one of the seven cohorts. In the meta-analysis, after adjustment for clinicopathological factors, variants in the MGMT (rs2308327; HR 0.90; p-value = 3.5 x 10(-2)) and IL4 (rs2070874; HR 1.22; p-value = 1.1 x 10(-3)) genes were confirmed to be associated with risk of PCSM. In analyses limited to men diagnosed with local or regional stage disease, a variant in AKT1, rs2494750, was also confirmed to be associated with PCSM risk (HR 0.81; p-value = 3.6 x 10(-2)). Conclusions This meta-analysis confirms the association of three genetic variants with risk of PCSM, providing further evidence that genetic background plays a role in PCa-specific survival. While these variants alone are not sufficient as prognostic biomarkers, these results may provide insights into the biological pathways modulating tumour aggressiveness.
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| 2. |
- Stepanauskas, R, et al.
(författare)
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Summer inputs of riverine nutrients to the Baltic Sea: Bioavailability and eutrophication relevance
- 2002
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Ingår i: Ecological Monographs. - 0012-9615. ; 72:4, s. 579-597
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Tidskriftsartikel (refereegranskat)abstract
- Most nitrogen and phosphorus transported by world rivers to the oceans is associated with dissolved organic matter. However, organic matter as a potential source of N and P has hitherto been largely neglected in studies of coastal microbial food webs. We examined 50 rivers, draining a major part of the Baltic Sea watershed, with respect to summer concentrations, chemical composition, and biological availability of N and P. The broad spectrum of rivers studied enabled us to assess whether the input of terrigenous organic matter can be an important nutrient source, at various levels of anthropogenic loading of inorganic N and P. Concentrations of total N and P ranged from 9 to 220 mumol/L and from 0.14 to 5.56 mumol/L, respectively, with the highest concentrations in the southern part of the Baltic Sea drainage area and in several rivers on the Finnish western coast. Urea and dissolved combined amino acids (DCAA) each constituted 4-20% of dissolved organic nitrogen (DON), while dissolved free amino acids (DFAA) made up <3% of DON. The contribution of urea and amino acids to the DON pool was inversely correlated with DON concentration. Bacterial regrowth bioassays in selected rivers demonstrated that similar to30% of DON and similar to75% of dissolved organic phosphorus (DOP) was potentially available to the indigenous bacterial assemblage of the Baltic Sea, and hence susceptible to mineralization within the pelagic food web. Our study is among the first to demonstrate that bacterioplankton are able to utilize a major part of DON and DOP from a broad spectrum of natural waters. The C:N ratio, absorbance spectra, and fluorescence properties of the organic matter suggest that the observed high bioavailability of DON and DOP was due to a large contribution of organic matter from riverine primary production compared to the humic matter derived from terrestrial vascular plants. In addition, algal and bacterial cells dominated the transport of particulate organic material, further enhancing productivity of coastal waters. No correlations were found between DON bioavailability and the fraction of DON bound in urea and amino acids, indicating a utilization of other N compounds (e.g., amides) by the bacteria. We estimate that the input of summer riverine N to the Baltic Sea consists of 48% dissolved inorganic N, 41 % DON, and 11 % particulate N. Corresponding values for phosphorus are 46%, 18%, and 36% of dissolved inorganic P, DOP, and particulate P, respectively. During the thermal summer stratification, when freshwater inputs are trapped in the surface layer, rivers contribute similar to30% of N and similar to5% of P needed to support the export production (plankton sedimenting out of the photic layer) in the Baltic Sea. The high availability to bacteria suggests that DOP is a major stimulator of pelagic productivity in the P-limited northern part of the Baltic Sea. Based on reported concentrations in other areas, we suggest that the global contribution of riverine organic N and P to the primary production of coastal waters is comparable to the contribution of inorganic nutrients.
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