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- Tabassum, R, et al.
(author)
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Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
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Journal article (peer-reviewed)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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- Naafs, B. D. A., et al.
(author)
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Introducing global peat-specific temperature and pH calibrations based on brGDGT bacterial lipids
- 2017
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In: Geochimica et Cosmochimica Acta. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0016-7037 .- 1872-9533. ; 208, s. 285-301
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Journal article (peer-reviewed)abstract
- Glycerol dialkyl glycerol tetraethers (GDGTs) are membrane-spanning lipids from Bacteria and Archaea that are ubiquitous in a range of natural archives and especially abundant in peat. Previous work demonstrated that the distribution of bacterial branched GDGTs (brGDGTs) in mineral soils is correlated to environmental factors such as mean annual air temperature (MAAT) and soil pH. However, the influence of these parameters on brGDGT distributions in peat is largely unknown. Here we investigate the distribution of brGDGTs in 470 samples from 96 peatlands around the world with a broad mean annual air temperature (-8 to 27 degrees C) and pH (3-8) range and present the first peat-specific brGDGT-based temperature and pH calibrations. Our results demonstrate that the degree of cyclisation of brGDGTs in peat is positively correlated with pH, pH = 2.49 x CBTpeat + 8.07 (n = 51, R-2 = 0.58, RMSE = 0.8) and the degree of methylation of brGDGTs is positively correlated with MAAT, MAAT(peat) (degrees C) = 52.18 x MBT'(5me) - 23.05 (n = 96, R-2 = 0.76, RMSE = 4.7 degrees C). These peat-specific calibrations are distinct from the available mineral soil calibrations. In light of the error in the temperature calibration (similar to 4.7 degrees C), we urge caution in any application to reconstruct late Holocene climate variability, where the climatic signals are relatively small, and the duration of excursions could be brief. Instead, these proxies are well-suited to reconstruct large amplitude, longer-term shifts in climate such as deglacial transitions. Indeed, when applied to a peat deposit spanning the late glacial period (similar to 15.2 kyr), we demonstrate that MAAT(peat) yields absolute temperatures and relative temperature changes that are consistent with those from other proxies. In addition, the application of MAAT(peat) to fossil peat (i.e. lignites) has the potential to reconstruct terrestrial climate during the Cenozoic. We conclude that there is clear potential to use brGDGTs in peats and lignites to reconstruct past terrestrial climate.
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- Pennanen, C, et al.
(author)
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The effect of apolipoprotein polymorphism on brain in mild cognitive impairment: a voxel-based morphometric study
- 2006
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In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 22:1, s. 60-66
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Journal article (peer-reviewed)abstract
- We investigated the effect of apolipoprotein E (ApoE) on the whole brain in 51 individuals with mild cognitive impairment using voxel-based morphometry. Between cases heterozygous for the ApoE Ε4 (n = 15) and those who were ApoE Ε4 noncarriers (n = 28), only the right parahippocampal gyrus, with the entorhinal cortex included, reached the level of statistical significance. In cases homozygous for the Ε4 allele (n = 8) versus noncarriers, the greatest atrophy was located in the right amygdala followed by the right parahippocampal gyrus, the left amygdala and the left medial dorsal thalamic nucleus.
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- Hedenfalk, I, et al.
(author)
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Gene-expression profiles in hereditary breast cancer
- 2001
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In: New England Journal of Medicine. - 0028-4793. ; 344:8, s. 48-539
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Journal article (peer-reviewed)abstract
- BACKGROUND: Many cases of hereditary breast cancer are due to mutations in either the BRCA1 or the BRCA2 gene. The histopathological changes in these cancers are often characteristic of the mutant gene. We hypothesized that the genes expressed by these two types of tumors are also distinctive, perhaps allowing us to identify cases of hereditary breast cancer on the basis of gene-expression profiles.METHODS: RNA from samples of primary tumor from seven carriers of the BRCA1 mutation, seven carriers of the BRCA2 mutation, and seven patients with sporadic cases of breast cancer was compared with a microarray of 6512 complementary DNA clones of 5361 genes. Statistical analyses were used to identify a set of genes that could distinguish the BRCA1 genotype from the BRCA2 genotype.RESULTS: Permutation analysis of multivariate classification functions established that the gene-expression profiles of tumors with BRCA1 mutations, tumors with BRCA2 mutations, and sporadic tumors differed significantly from each other. An analysis of variance between the levels of gene expression and the genotype of the samples identified 176 genes that were differentially expressed in tumors with BRCA1 mutations and tumors with BRCA2 mutations. Given the known properties of some of the genes in this panel, our findings indicate that there are functional differences between breast tumors with BRCA1 mutations and those with BRCA2 mutations.CONCLUSIONS: Significantly different groups of genes are expressed by breast cancers with BRCA1 mutations and breast cancers with BRCA2 mutations. Our results suggest that a heritable mutation influences the gene-expression profile of the cancer.
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- Julkunen, V, et al.
(author)
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Cortical thickness analysis to detect progressive mild cognitive impairment: a reference to Alzheimer's disease
- 2009
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In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:5, s. 404-412
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Journal article (peer-reviewed)abstract
- <i>Background/Aims:</i> Mild cognitive impairment (MCI) is associated with an increased risk of Alzheimer’s disease (AD). It would be advantageous to be able to distinguish the characteristics of those MCI patients with a high probability to progress to AD if one wishes to monitor the disease development and treatment. <i>Methods:</i> We assessed the baseline MRI and maximum of 7 years clinical follow-up data of 60 MCI subjects in order to examine differences in cortical thickness (CTH) between the progressive MCI (P-MCI) and stable MCI (S-MCI) subjects. CTH was measured using an automatic computational surface-based method. During the follow-up, 15 MCI subjects converted to AD on average 1.9 ± 1.3 years after the baseline examination, while 45 MCI subjects remained stable. <i>Results:</i> The P-MCI group displayed significantly reduced CTH bilaterally in the superior and middle frontal, superior, middle and inferior temporal, fusiform and parahippocampal regions as well as the cingulate and retrosplenial cortices and also in the right precuneal and paracentral regions compared to S-MCI subjects. <i>Conclusions:</i> Analysis of CTH could be used in conjunction with neuropsychological testing to identify those subjects with imminent conversion from MCI to AD several years before dementia diagnosis.
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- Liukkonen, J, et al.
(author)
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Salivary biomarkers in association with periodontal parameters and the periodontitis risk haplotype
- 2018
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In: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; 24:7, s. 439-447
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Journal article (peer-reviewed)abstract
- Genetic factors play a role in periodontitis. Here we examined whether the risk haplotype of MHC class III region BAT1-NFKBIL1-LTA and lymphotoxin-α polymorphisms associate with salivary biomarkers of periodontal disease. A total of 455 individuals with detailed clinical and radiographic periodontal health data were included in the study. A 610 K genotyping chip and a Sequenom platform were used in genotyping analyses. Phospholipid transfer protein activity, concentrations of lymphotoxin-α, IL-8 and myeloperoxidase, and a cumulative risk score (combining Porphyromonas gingivalis, IL-1β and matrix metalloproteinase-8) were examined in saliva samples. Elevated IL-8 and myeloperoxidase concentrations and cumulative risk scores associated with advanced tooth loss, deepened periodontal pockets and signs of periodontal inflammation. In multiple logistic regression models adjusted for periodontal parameters and risk factors, myeloperoxidase concentration (odds ratio (OR); 1.37, P = 0.007) associated with increased odds for having the risk haplotype and lymphotoxin-α concentration with its genetic variants rs2857708, rs2009658 and rs2844482. In conclusion, salivary levels of IL-8, myeloperoxidase and cumulative risk scores associate with periodontal inflammation and tissue destruction, while those of myeloperoxidase and lymphotoxin-α associate with genetic factors as well.
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- Liukkonen, J, et al.
(author)
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Immunological and Microbiological Profiling of Cumulative Risk Score for Periodontitis
- 2020
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In: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 10:8
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Journal article (peer-reviewed)abstract
- The cumulative risk score (CRS) is a mathematical salivary diagnostic model to define an individual’s risk of having periodontitis. In order to further validate this salivary biomarker, we investigated how periodontal bacteria, lipopolysaccharide (LPS), and systemic and local host immune responses relate to CRS. Subgingival plaque, saliva, and serum samples collected from 445 individuals were used in the analyses. Plaque levels of 28 microbial species, especially those of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, and Tannerella forsythia, and serum and salivary levels of IgA and IgG against these five species were determined. Additionally, LPS activity was measured. High CRS associated strongly with all IgA/IgG antibody and LPS levels in saliva, whereas in serum the associations were not that obvious. In the final logistic regression model, the best predictors of high CRS were saliva IgA burden against the five species (OR 7.04, 95% CI 2.25–22.0), IgG burden (3.79, 1.78–8.08), LPS (2.19, 1.38–3.47), and the sum of 17 subgingival Gram-negative species (6.19, 2.10–18.3). CRS is strongly associated with microbial biomarker species of periodontitis and salivary humoral immune responses against them.
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- Rautava, J, et al.
(author)
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An Oral Rinse Active Matrix Metalloproteinase-8 Point-of-Care Immunotest May Be Less Accurate in Patients with Crohn's Disease
- 2020
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In: Biomolecules. - : MDPI AG. - 2218-273X. ; 10:3
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Journal article (peer-reviewed)abstract
- The diagnostic accuracy of point-of-care (PoC) applications may be compromised in individuals with additional inflammatory conditions. This cross-sectional study examined the performance of a commercial oral rinse active matrix metalloproteinase-8 (aMMP-8) PoC immunotest in individuals with (n = 47) and without Crohn’s disease (CD) (n = 41). Oral rinse collected from the participants was analyzed by the PoC immunotest. Molecular forms and fragments of salivary MMP-8 were detected by western immunoblotting. The sensitivity of the immunotest for periodontitis was 60.0% in the CD group and 90.0% in the control group. The respective specificity was 75.0% and 80.0%. In both groups, clinical diagnosis of periodontitis exhibited a significant association with the immunotest results, however, the odds ratio (OR) was more than ten-fold in controls (OR 54.3, 95% CI: 3.1–953, p = 0.006) in comparison to CD patients (OR 5.2, 95% CI: 1.3–21.6, p = 0.022). According to Western immunoblot results, the immunotest MMP-8 positivity was not related to elevated levels of molecular forms and fragments of MMP-8 in the CD group, as in the control group. The diagnostic accuracy of the aMMP-8 PoC oral rinse immunotest is reduced in CD patients, which may be related to lower levels or undetectable complexes.
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- Sorsa, T, et al.
(author)
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Host-Modulation Therapy and Chair-Side Diagnostics in the Treatment of Peri-Implantitis
- 2020
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In: Biosensors. - : MDPI AG. - 2079-6374. ; 10:5
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Journal article (peer-reviewed)abstract
- Previous studies report periodontitis and peri-implantitis being able to induce systemic low-grade inflammation, which is known to be associated with increased risk for some systemic medical disease such as cardiovascular disease. In this regard, recent studies have shown that host modulation therapy (HMT) together with traditional mechanical and surgical treatment not only cease the progression of periodontitis but also reduce the systemic collagenolytic biomarkers in both oral fluids and circulation. This suggests that the corresponding adjunctive HMT-medication could be effective in the prevention and treatment of dental peri-implantitis, as well. Furthermore, low-cost, safe, and practical oral fluid active matrix metalloproteinase-8 (aMMP-8) lateral-flow immunotests have been proposed as point-of-care/chair-side diagnostic tools to detect peri-implantitis and periodontitis, and to monitor their effective resolutions, while using various therapeutic strategies, including host modulation. This study reports the potential benefits of HMT-medication in the prevention and treatment of dental peri-implantitis among five patients (four of five were current/ex-smokers). In addition, the aMMP-8 point-of-care test diagnosed 20 peri-implantitis and 20 healthy controls correctly. In conclusion, this study and previous studies support the potential effectiveness of HMT-medication(s) and point-of-care/chair-side technologies in the treatment and diagnostics/monitoring of peri-implantitis. However, more studies are needed to further confirm this.
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- Toivonen, P, et al.
(author)
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Cavum septum pellucidum and psychopathy
- 2013
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In: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 203:2, s. 152-153
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Journal article (peer-reviewed)abstract
- The presence of cavum septum pellucidum (CSP) has been reported to be a neurodevelopmental marker of psychopathy. We scanned 26 violent offenders and 25 controls; 2 offenders and 2 controls had CSP (8% in both groups). Thus, the presence of CSP is not a common or a unique feature of antisocial personality disorder or psychopathy.
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