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| 2. |
- Manuguerra, M., et al.
(författare)
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Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions
- 2007
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 28:2, s. 414-422
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Tidskriftsartikel (refereegranskat)abstract
- It is becoming increasingly evident that single-locus effects cannot explain complex multifactorial human diseases like cancer. We applied the multi-factor dimensionality reduction (MDR) method to a large cohort study on gene-environment and gene-gene interactions. The study (case-control nested in the EPIC cohort) was established to investigate molecular changes and genetic susceptibility in relation to air pollution and environmental tobacco smoke (ETS) in non-smokers. We have analyzed 757 controls and 409 cases with bladder cancer (n = 124), lung cancer (n = 116) and myeloid leukemia (n = 169). Thirty-six gene variants (DNA repair and metabolic genes) and three environmental exposure variables (measures of air pollution and ETS at home and at work) were analyzed. Interactions were assessed by prediction error percentage and cross-validation consistency (CVC) frequency. For lung cancer, the best model was given by a significant gene-environment association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism, the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the exposure variable 'distance from heavy traffic road', an indirect and robust indicator of air pollution (mean prediction error of 26%, P < 0.001, mean CVC of 6.60, P = 0.02). For bladder cancer, we found a significant 4-loci association between the BER APE1-Asp148Glu polymorphism, the DSBR RAD52-3'-untranslated region (3'-UTR) polymorphism and the metabolic gene polymorphisms COMT-Val158Met and MTHFR-677C > T (mean prediction error of 22%, P < 0.001, mean CVC consistency of 7.40, P < 0.037). For leukemia, a 3-loci model including RAD52-2259C > T, MnSOD-Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P < 0.001) and a maximum CVC of 4.40 (P = 0.086). The MDR method seems promising, because it provides a limited number of statistically stable interactions; however, the biological interpretation remains to be understood.
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| 4. |
- Moschella, P. S., et al.
(författare)
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Low-crested coastal defence structures as artificial habitats for marine life: Using ecological criteria in design
- 2005
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Ingår i: Coastal Engineering. - : Elsevier BV. - 0378-3839. ; 52:10-11, s. 1053-1071
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Tidskriftsartikel (refereegranskat)abstract
- Coastal defence structures to protect sedimentary coastlines from erosion and flooding are increasingly common throughout Europe. They will become more widespread over the next 10-30 years in response to rising and stormier seas and accelerating economic development of the coastal zone. Building coastal defences results in the loss and fragmentation of sedimentary habitats and their replacement by artificial rocky habitats that become colonised by algae and marine animals. The engineering design and construction of these structures have received considerable attention. However, the ecological consequences of coastal defences have been less extensively investigated. Furthermore, due to their rapid proliferation, there is a growing need to understand the role of these man-made habitats in the coastal ecosystems in order to implement impact minimisation and/or mitigation measures. As part of the DELOS project, targeted studies were carried out throughout Europe to assess the ecological similarity of low-crested coastal defence structures (LCS) to natural rocky shores and to investigate the influence of LCS design features on the colonising marine epibiota. LCSs can be considered as a relatively poor surrogate of natural rocky shores. Epibiotic communities were qualitatively similar to those on natural rocky shores as both habitats are regulated by the same physical and biological factors. However, there were quantitative differences in the diversity and abundance of epibiota on artificial structures. Typically, epibiotic assemblages were less diverse than rocky shore communities. Also, LCSs offered less structurally complex habitats for colonisation and in some locations experienced higher disturbance than natural shores. We propose several criteria that can be integrated into the design and construction of LCSs to minimise ecological impacts and allow targeted management of diversity and natural living resources. (c) 2005 Elsevier B.V. All rights reserved.
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| 6. |
- Vineis, P., et al.
(författare)
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Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers
- 2007
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 18:7, s. 1230-1242
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Tidskriftsartikel (refereegranskat)abstract
- Background: We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene-environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia). Patients and methods: The study has been conducted as a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase 11 metabolizing genes and methylenetetrahydrofolate reductase (MTHFR). Results: The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55.
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| 7. |
- Hopper, I., et al.
(författare)
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Sympathetic Response and Outcomes Following Renal Denervation in Patients With Chronic Heart Failure: 12-Month Outcomes From the Symplicity HF Feasibility Study
- 2017
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Ingår i: Journal of Cardiac Failure. - : Elsevier BV. - 1071-9164. ; 23:9, s. 702-707
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heart failure (HF) is associated with chronic sympathetic activation. Renal denervation (RDN) aims to reduce sympathetic activity by ablating the renal sympathetic nerves. We investigated the effect of RDN in patients with chronic HF and concurrent renal dysfunction in a prospective, multicenter, single-arm feasibility study. Methods and Results: Thirty-nine patients with chronic systolic HF (left ventricular ejection fraction [LVEF] <40%, New York Heart Association class II-III,) and renal impairment (estimated glomerular filtration rate [eGFR; assessed with the use of the Modification of Diet in Renal Disease equation] < 75 mL . min(-1) . 1.73 m(-2)) on stable medical therapy were enrolled. Mean age was 65 +/- 11 years; 62% had ischemic HF. The average number of ablations per patient was 13 +/- 3. No protocol-defined safety events were associated with the procedure. One subject experienced a renal artery occlusion that was possibly related to the denervation procedure. Statistically significant reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP; 1530 +/- 1228 vs 1428 +/- 1844 ng/mL; P = .006) and 120-minute glucose tolerance test (11.2 +/- 5.1 vs 9.9 +/- 3.6; P = .026) were seen at 12 months, but there was no significant change in LVEF (28 +/- 9% vs 29 +/- 11%; P = .536), 6-minute walk test (384 +/- 96 vs 391 +/- 97 m; P = .584), or eGFR (52.6 +/- 15.3 vs 52.3 +/- 18.5 mL . min(-1) . 1.73 m(-2); P = .700). Conclusions: RDN was associated with reductions in NT-proBNP and 120-minute glucose tolerance test in HF patients 12 months after RDN treatment. There was no deterioration in other indices of cardiac and renal function in this small feasibility study.
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| 8. |
- Morandi, F, et al.
(författare)
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CD38, a Receptor with Multifunctional Activities: From Modulatory Functions on Regulatory Cell Subsets and Extracellular Vesicles, to a Target for Therapeutic Strategies
- 2019
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- CD38 is a multifunctional cell surface protein endowed with receptor/enzymatic functions. The protein is generally expressed at low/intermediate levels on hematological tissues and some solid tumors, scoring the highest levels on plasma cells (PC) and PC-derived neoplasia. CD38 was originally described as a receptor expressed by activated cells, mainly T lymphocytes, wherein it also regulates cell adhesion and cooperates in signal transduction mediated by major receptor complexes. Furthermore, CD38 metabolizes extracellular NAD+, generating ADPR and cyclic ADPR. This ecto-enzyme controls extra-cellular nucleotide homeostasis and intra-cellular calcium fluxes, stressing its relevance in multiple physiopathological conditions (infection, tumorigenesis and aging). In clinics, CD38 was adopted as a cell activation marker and in the diagnostic/staging of leukemias. Quantitative surface CD38 expression by multiple myeloma (MM) cells was the basic criterion used for therapeutic application of anti-CD38 monoclonal antibodies (mAbs). Anti-CD38 mAbs-mediated PC depletion in autoimmunity and organ transplants is currently under investigation. This review analyzes different aspects of CD38’s role in regulatory cell populations and how these effects are obtained. Characterizing CD38 functional properties may widen the extension of therapeutic applications for anti-CD38 mAbs. The availability of therapeutic mAbs with different effects on CD38 enzymatic functions may be rapidly translated to immunotherapeutic strategies of cell immune defense.
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| 9. |
- Moyroud, Edwige, et al.
(författare)
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Cuticle chemistry drives the development of diffraction gratings on the surface of Hibiscus trionum petals
- 2022
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:24, s. 5323-5334, 5323-5334.e1-e6
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Tidskriftsartikel (refereegranskat)abstract
- Plants combine both chemical and structural means to appear colorful. We now have an extensive understanding of the metabolic pathways used by flowering plants to synthesize pigments, but the mechanisms remain obscure whereby cells produce microscopic structures sufficiently regular to interfere with light and create an optical effect. Here, we combine transgenic approaches in a novel model system, Hibiscus trionum, with chemical analyses of the cuticle, both in transgenic lines and in different species of Hibiscus, to investigate the formation of a semi-ordered diffraction grating on the petal surface. We show that regulating both cuticle production and epidermal cell growth is insufficient to determine the type of cuticular pattern produced. Instead, the chemical composition of the cuticle plays a crucial role in restricting the formation of diffraction gratings to the pigmented region of the petal. This suggests that buckling, driven by spatiotemporal regulation of cuticle chemistry, could pattern the petal surface at the nanoscale.
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| 10. |
- Stuart-Smith, Rick D., et al.
(författare)
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Integrating abundance and functional traits reveals new global hotspots of fish diversity
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 501:7468, s. 539-
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Tidskriftsartikel (refereegranskat)abstract
- Species richness has dominated our view of global biodiversity patterns for centuries(1,2). The dominance of this paradigm is reflected in the focus by ecologists and conservation managers on richness and associated occurrence-based measures for understanding drivers of broad-scale diversity patterns and as a biological basis for management(3,4). However, this is changing rapidly, as it is now recognized that not only the number of species but the species present, their phenotypes and the number of individuals of each species are critical in determining the nature and strength of the relationships between species diversity and a range of ecological functions (such as biomass production and nutrient cycling)(5). Integrating these measures should provide a more relevant representation of global biodiversity patterns in terms of ecological functions than that provided by simple species counts. Here we provide comparisons of a traditional global biodiversity distribution measure based on richness with metrics that incorporate species abundances and functional traits. We use data from standardized quantitative surveys of 2,473 marine reef fish species at 1,844 sites, spanning 133 degrees of latitude from all ocean basins, to identify new diversity hotspots in some temperate regions and the tropical eastern Pacific Ocean. These relate to high diversity of functional traits amongst individuals in the community (calculated using Rao's Q(6)), and differ from previously reported patterns in functional diversity and richness for terrestrial animals, which emphasize species-rich tropical regions only(7,8). There is a global trend for greater evenness in the number of individuals of each species, across the reef fish species observed at sites ('community evenness'), at higher latitudes. This contributes to the distribution of functional diversity hotspots and contrasts with well-known latitudinal gradients in richness(2,4). Our findings suggest that the contribution of species diversity to a range of ecosystem functions varies over large scales, and imply that in tropical regions, which have higher numbers of species, each species contributes proportionally less to community-level ecological processes on average than species in temperate regions. Metrics of ecological function usefully complement metrics of species diversity in conservation management, including when identifying planning priorities and when tracking changes to biodiversity values.
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| 11. |
- Stuart-Smith, Rick D., et al.
(författare)
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The potential of trait-based approaches to contribute to marine conservation
- 2015
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Ingår i: Marine Policy. - : Elsevier BV. - 0308-597X .- 1872-9460. ; 51, s. 148-150
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Tidskriftsartikel (refereegranskat)abstract
- The value of diversity metrics to represent ecological communities and inform broad-scale conservation objectives and policy has often been subject to debate and uncertainty [1,2]. In practice, diversity metrics are important in setting management and conservation priorities, just as economic indices contribute to global monetary and financial policies. Thus, key challenges for ecologists are to identify new ways to view and summarise patterns in biodiversity and improve on the metrics available for management purposes. In a recent paper on functional diversity patterns in reef fishes [3], we highlighted the potential of new insights gained from functional trait-based approaches to inform marine management, stressing the need to develop and refine biodiversity measures that are linked to ecology (rather than taxonomy). We used a unique, fisheries-independent reef fish identity and abundance dataset, collected using standardised methods from equatorial to high latitude regions all over the world, to provide the first global view of the distribution of individuals amongst species (including a measure of evenness) and functional traits amongst marine communities. A recent paper by Robinson et al. [4] published in Marine Policy criticised the use of our evenness index as a measure of biodiversity, and questioned the use of functional trait-based metrics derived from surveys of standardised areas for decisions relating to broad-scale management of marine systems. In this paper we respond to Robinson et al. and rebut their claims related to sampling bias and broad-scale applicability of trait-based approaches.
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| 12. |
- Vaissière, Thomas, et al.
(författare)
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Quantitative analysis of DNA methylation after whole bisulfitome amplification of a minute amount of DNA from body fluids.
- 2009
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Ingår i: Epigenetics : official journal of the DNA Methylation Society. - 1559-2308. ; 4:4, s. 221-30
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Tidskriftsartikel (refereegranskat)abstract
- Cell-free circulating DNA isolated from the plasma of individuals with cancer has been shown to harbor cancer-associated changes in DNA methylation, and thus it represents an attractive target for biomarker discovery. However, the reliable detection of DNA methylation changes in body fluids has proven to be technically challenging. Here we describe a novel combination of methods that allows quantitative and sensitive detection of DNA methylation in minute amounts of DNA present in body fluids (quantitative Methylation Analysis of Minute DNA amounts after whole Bisulfitome Amplification, qMAMBA). This method involves genome-wide amplification of bisulphite-modified DNA template followed by quantitative methylation detection using pyrosequencing and allows analysis of multiple genes from a small amount of starting DNA. To validate our method we used qMAMBA assays for four genes and LINE1 repetitive sequences combined with plasma DNA samples as a model system. qMAMBA offered high efficacy in the analysis of methylation levels and patterns in plasma samples with extremely small amounts of DNA and low concentrations of methylated alleles. Therefore, qMAMBA will facilitate methylation studies aiming to discover epigenetic biomarkers, and should prove particularly valuable in profiling a large sample series of body fluids from molecular epidemiology studies as well as in tracking disease in early diagnostics.
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