| 11. |
- Gram, Inger T, et al.
(author)
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Cigarette smoking and risk of histological subtypes of epithelial ovarian cancer in the EPIC cohort study
- 2012
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 130:9, s. 2204-2210
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Journal article (peer-reviewed)abstract
- New data regarding a positive association between smoking and risk of epithelial ovarian cancer (EOC), especially the mucinous tumor type, has started to emerge. The purpose of this study was to examine the association between different measures of smoking exposures and subtypes of EOC in a large cohort of women from 10 European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort is a multicenter prospective study initiated in 1992. The questionnaires included data about dietary, lifestyle, and health factors. Information about cigarette smoking was collected from individuals in all participating countries. We used Cox proportional hazard regression models to estimate hazard ratio (HR) of EOC overall and serous, mucinous, and endometroid histological subtypes, with 95% confidence intervals (CIs) associated with different measures of smoking exposures adjusting for confounding variables. Altogether 836 incident EOC cases were identified among 326,831 women. The tumors were classified as 400 serous, 83 mucinous, 80 endometroid, 35 clear cell, and 238 unspecified. Compared with never smokers, current smokers had a significantly increased risk for mucinous tumors [HR = 1.85 (95% CI 1.08-3.16)] and those smoking more than 10 cigarettes per day had a doubling in risk [HR = 2.25(95% CI 1.26-4.03)] as did those who had smoked less than 15 pack-years of cigarettes [HR = 2.18 (95% CI 1.07-4.43)]. The results from the EPIC study add further evidence that smoking increases risk of mucinous ovarian cancer and support the notion that the effect of smoking varies according to histological subtype.
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| 12. |
- Grote, Verena A., et al.
(author)
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The association of circulating adiponectin levels with pancreatic cancer risk: A study within the prospective EPIC cohort
- 2012
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 130, s. 2428-2437
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Journal article (peer-reviewed)abstract
- Excess body weight and type 2 diabetes mellitus, risk factors of pancreatic cancer, are characterized by decreased levels of adiponectin. In addition to anti-inflammatory and anti-proliferative actions, adiponectin has an important role in regulating glucose metabolism, i.e., decreasing circulating blood glucose levels. Prospectively, hyperglycemia has been associated with risk of pancreatic cancer. The aim of this study was to investigate the association of pre-diagnostic adiponectin levels with pancreatic cancer risk. We conducted a case-control study nested within European Prospective Investigation into Cancer and Nutrition. Blood samples of 452 pancreatic cancer cases and 452 individually matched controls were analyzed by immunoassays. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, adiponectin showed no association with pancreas cancer risk; however, among never smokers, higher circulating levels of adiponectin were associated with a reduction in pancreatic cancer risk (OR = 0.44 [95% CI 0.23-0.82] for highest vs. lowest quartile), whereas among current smokers there was no significant association (OR = 1.59 [95% CI 0.67-3.76] for highest vs. lowest quartile; p-trend = 0.530; p-interaction = 0.309). In our study, lower adiponectin concentrations may be associated with the development of pancreatic cancer among never smokers, whereas the only other prospective study being conducted so far showed a decrease in risk among male smokers. Therefore, further studies are needed to clarify the role of adiponectin in pancreatic cancer development. © 2011 UICC.
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| 13. |
- Konyukh, Marina, et al.
(author)
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Variations of the candidate SEZ6L2 gene on Chromosome 16p11.2 in patients with autism spectrum disorders and in human populations.
- 2011
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In: PLoS One. - : Public Library of Science (PLoS). - 1932-6203. ; 6:3
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Journal article (peer-reviewed)abstract
- Background Autism spectrum disorders (ASD) are a group of severe childhood neurodevelopmental disorders with still unknown etiology. One of the most frequently reported associations is the presence of recurrent de novo or inherited microdeletions and microduplications on chromosome 16p11.2. The analysis of rare variations of 8 candidate genes among the 27 genes located in this region suggested SEZ6L2 as a compelling candidate. Methodology/Principal Findings We further explored the role of SEZ6L2 variations by screening its coding part in a group of 452 individuals, including 170 patients with ASD and 282 individuals from different ethnic backgrounds of the Human Genome Diversity Panel (HGDP), complementing the previously reported screening. We detected 7 previously unidentified non-synonymous variations of SEZ6L2 in ASD patients. We also identified 6 non-synonymous variations present only in HGDP. When we merged our results with the previously published, no enrichment of non-synonymous variation in SEZ6L2 was observed in the ASD group compared with controls. Conclusions/Significance Our results provide an extensive ascertainment of the genetic variability of SEZ6L2 in human populations and do not support a major role for SEZ6L2 sequence variations in the susceptibility to ASD.
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| 14. |
- Leblond, Claire S, et al.
(author)
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Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.
- 2012
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In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:2
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Journal article (peer-reviewed)abstract
- Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n=396 patients and n=659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P=0.004, OR=2.37, 95% CI=1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P=0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.
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| 15. |
- Oumata, Nassima, et al.
(author)
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The Toll-Like Receptor Agonist Imiquimod Is Active against Prions
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8, s. e72112-
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Journal article (peer-reviewed)abstract
- Using a yeast-based assay, a previously unsuspected antiprion activity was found for imiquimod (IQ), a potent Toll-like receptor 7 (TLR7) agonist already used for clinical applications. The antiprion activity of IQ was first detected against yeast prions [PSI+] and [URE3], and then against mammalian prion both ex vivo in a cell-based assay and in vivo in a transgenic mouse model for prion diseases. In order to facilitate structure-activity relationship studies, we conducted a new synthetic pathway which provides a more efficient means of producing new IQ chemical derivatives, the activity of which was tested against both yeast and mammalian prions. The comparable antiprion activity of IQ and its chemical derivatives in the above life forms further emphasizes the conservation of prion controlling mechanisms throughout evolution. Interestingly, this study also demonstrated that the antiprion activity of IQ and IQ-derived compounds is independent from their ability to stimulate TLRs. Furthermore, we found that IQ and its active chemical derivatives inhibit the protein folding activity of the ribosome (PFAR) in vitro.
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| 16. |
- Pluchon, Nathalie, et al.
(author)
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Stimulation of boreal tree seedling growth by wood-derived charcoal: effects of charcoal properties, seedling species and soil fertility
- 2014
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In: Functional Ecology. - : Wiley. - 0269-8463 .- 1365-2435. ; 28, s. 766-775
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Journal article (peer-reviewed)abstract
- Fire is a major disturbance in many ecosystems world-wide including the boreal forest, and significant quantities of charcoal can be input to the soil from fire. Some recent studies have provided evidence that wood-derived charcoal produced by fire can significantly stimulate plant growth. However, the mechanisms by which charcoal affects plant growth are poorly understood, and little is known about how charcoal effects on plant growth are influenced by charcoal type, soil type and plant species.Seedlings from four common boreal tree species, two evergreen gymnosperms and two deciduous angiosperms, were grown in each of two soils of contrasting nutrient availability amended with charcoal with each of nine charcoal types (each produced from wood from a different plant species) in a greenhouse experiment. We also measured several functional traits for each of the charcoal types, as well as of the wood used to prepare the charcoal.Charcoal addition had either positive or neutral effects on seedling growth, with great variability among charcoal types. The charcoal types that had the strongest positive effect were those that had the greatest concentrations of phosphate and total phosphorus and, in some cases, were derived from woods that had the highest total phosphorus concentration. Addition of charcoal on average had a stronger positive effect on plant growth on soil with the lowest levels of phosphate and total phosphorus.Generally, charcoal derived from angiosperms stimulated seedling growth more than charcoal from gymnosperms. Further, angiosperm seedlings were on average stimulated more by charcoal addition than were gymnosperm seedlings. These results indicate that charcoal produced by fire could contribute to the initial dominance of angiosperm trees in post-fire succession and suggest a possible feedback whereby charcoal from angiosperm tree species favours growth of angiosperm seedlings.This study highlights a new means by which functional trait variation among tree species could potentially exert 'after-life' effects in forested ecosystems through influencing traits (and notably phosphate concentrations) of the charcoal that they produce following wildfire, with potentially important consequences for plant growth and community and ecosystem properties during post-fire succession.
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| 17. |
- Roe, Amanda D., et al.
(author)
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Fitness dynamics within a poplar hybrid zone : II. Impact of exotic sex on native poplars in an urban jungle
- 2014
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In: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:10, s. 1876-1889
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Journal article (peer-reviewed)abstract
- Trees bearing novel or exotic gene components are poised to contribute to the bioeconomy for a variety of purposes such as bioenergy production, phytoremediation, and carbon sequestration within the forestry sector, but sustainable release of trees with novel traits in large-scale plantations requires the quantification of risks posed to native tree populations. Over the last century, exotic hybrid poplars produced through artificial crosses were planted throughout eastern Canada as ornamentals or windbreaks and these exotics provide a proxy by which to examine the fitness of exotic poplar traits within the natural environment to assess risk of exotic gene escape, establishment, and spread into native gene pools. We assessed postzygotic fitness traits of native and exotic poplars within a naturally regenerated stand in eastern Canada (Quebec City, QC). Pure natives (P.balsamifera and P.deltoides spp. deltoides), native hybrids (P.deltoidesxP.balsamifera), and exotic hybrids (trees bearing Populus nigra and P.maximowiczii genetic components) were screened for reproductive biomass, yield, seed germination, and fungal disease susceptibility. Exotic hybrids expressed fitness traits intermediate to pure species and were not significantly different from native hybrids. They formed fully viable seed and backcrossed predominantly with P.balsamifera. These data show that exotic hybrids were not unfit and were capable of establishing and competing within the native stand. Future research will seek to examine the impact of exotic gene regions on associated biotic communities to fully quantify the risk exotic poplars pose to native poplar forests.
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| 18. |
- Roe, Amanda D., et al.
(author)
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Fitness dynamics within a poplar hybrid zone : I. Prezygotic and postzygotic barriers impacting a native poplar hybrid stand
- 2014
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In: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:9, s. 1629-1647
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Journal article (peer-reviewed)abstract
- Hybridization and introgression are pervasive evolutionary phenomena that provide insight into the selective forces that maintain species boundaries, permit gene flow, and control the direction of evolutionary change. Poplar trees (Populus L.) are well known for their ability to form viable hybrids and maintain their distinct species boundaries despite this interspecific gene flow. We sought to quantify the hybridization dynamics and postzygotic fitness within a hybrid stand of balsam poplar (Populus balsamifera L.), eastern cottonwood (P.deltoides Marsh.), and their natural hybrids to gain insight into the barriers maintaining this stable hybrid zone. We observed asymmetrical hybrid formation with P.deltoides acting as the seed parent, but with subsequent introgression biased toward P.balsamifera. Native hybrids expressed fitness traits intermediate to the parental species and were not universally unfit. That said, native hybrid seedlings were absent from the seedling population, which may indicate additional selective pressures controlling their recruitment. It is imperative that we understand the selective forces maintaining this native hybrid zone in order to quantify the impact of exotic poplar hybrids on this native system.
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| 19. |
- Sanches, Pedro, et al.
(author)
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Mind the body! : designing a mobile stress management application encouraging personal reflection
- 2010
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In: Proceedings of the 8th ACM conference on designing interactive systems. - New York, NY, USA : Association for Computing Machinery (ACM). ; , s. 47-56
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Conference paper (peer-reviewed)abstract
- We have designed a stress management biofeedback mobile service for everyday use, aiding users to reflect on both positive and negative patterns in their behavior. To do so, we embarked on a complex multidisciplinary design journey, learning that: detrimental stress results from complex processes related to e.g. the subjective experience of being able to cope (or not) and can therefore not be measured and diagnosed solely as a bodily state. We learnt that it is difficult, sometimes impossible, to make a robust analysis of stress symptoms based on biosensors worn outside the laboratory environment they were designed for. We learnt that rather than trying to diagnose stress, it is better to mirror short-term stress reactions back to them, inviting their own interpretations and reflections. Finally, we identified several experiential qualities that such an interface should entail: ambiguity and openness to interpretation, interactive history of prior states, fluency and aliveness.
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| 20. |
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