| 1. |
- Smith, Jennifer A, et al.
(author)
-
Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
-
In: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
-
Journal article (peer-reviewed)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
|
|
| 2. |
- Bradley, E. L., et al.
(author)
-
The BIOSAFEPAPER project for in vitro toxicity assessments : Preparation, detailed chemical characterisation and testing of extracts from paper and board samples
- 2008
-
In: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 46:7, s. 2498-2509
-
Journal article (peer-reviewed)abstract
- Nineteen food contact papers and boards and one non-food contact board were extracted following test protocols developed within European Union funded project BIOSAFEPAPER. The extraction media were either hot or cold water, 95% ethanol or Tenax, according to the end use of the sample. The extractable dry matter content of the samples varied from 1200 to 11,800 mg/kg (0.8-35.5 mg/dm2). According to GC-MS the main substances extracted into water were pulp-derived natural products such as fatty acids, resin acids, natural wood sterols and alkanols. Substances extracted into ethanol particularly, were diisopropylnaphthalenes, alkanes and phthalic acid esters. The non-food contact board showed the greatest number and highest concentrations of GC-MS detectable compounds. The extracts were subjected to a battery of in vitro toxicity tests measuring both acute and sublethal cytotoxicity and genotoxic effects. None of the water or Tenax extracts was positive in cytotoxicity or genotoxicity assays. The ethanol extract of the non-food contact board gave a positive response in the genotoxicity assays, and all four ethanol extracts gave positive response(s) in the cytotoxicity assays to some extent. These responses could not be pinpointed to any specific compound, although there appeared a correlation between the total amount of extractables and toxicity.
|
|
| 3. |
- Honkalampi-Hämäläinen, U., et al.
(author)
-
Safety evaluation of food contact paper and board using chemical tests and in vitro bioassays : Role of known and unknown substances
- 2010
-
In: Food Additives and Contaminants. - : Informa UK Limited. - 0265-203X .- 1464-5122. ; 27:3, s. 406-115
-
Journal article (peer-reviewed)abstract
- In vitro toxicological tests have been proposed as an approach to complement the chemical safety assessment of food contact materials, particularly those with a complex or unknown chemical composition such as paper and board. Among the concerns raised regarding the applicability of in vitro tests are the effects of interference of the extractables on the outcome of the cytotoxicity and genotoxicity tests applied and the role of known compounds present in chemically complex materials, such as paper and board, either as constituents or contaminants. To answer these questions, a series of experiments were performed to assess the role of natural substances (wood extracts, resin acids), some additives (diisopropylnaphthalene, phthalates, acrylamide, fluorescent whitening agents) and contaminants (2,4-diaminotoluene, benzo[a]pyrene) in the toxicological profile of paper and board. These substances were individually tested or used to spike actual paper and board extracts. The toxic concentrations of diisopropylnaphthalenes and phthalates were compared with those actually detected in paper and board extracts showing conspicuous toxicity. According to the results of the spiking experiments, the extracts did not affect the toxicity of tested chemicals nor was there any significant metabolic interference in the cases where two compounds were used in tests involving xenobiotic metabolism by the target cells. While the identified substances apparently have a role in the cytotoxicity of some of the project samples, their presence does not explain the total toxicological profile of the extracts. In conclusion, in vitro toxicological testing can have a role in the safety assessment of chemically complex materials in detecting potentially harmful activities not predictable by chemical analysis alone.
|
|
| 4. |
- Kirilin, A, et al.
(author)
-
Mechanistic investigations of the reaction network in chemobiocatalyzed synthesis of R1Phenylethyl Acetate
- 2010
-
In: Kinetics and catalysis. - : Springer. - 0023-1584 .- 1608-3210. ; 51:6, s. 809-815
-
Journal article (peer-reviewed)abstract
- The kinetics and reaction network of the onepot synthesis of R1phenylethyl acetate was investigated at 70°C in toluene over a combination of three different catalysts: PdZn/Al2O3 as a catalyst for acetophenone hydrogenation, lipase as an enzymatic catalyst for R1phenylethanol acylation with ethyl acetate and Ru/Al2O3 as a racemization catalyst for S1phenylethanol. In addition to the desired reactions, other reactions, namely hydrogenolysis and dehydration of (R, S)1phenylethanol and debenzylation of (R, S)1phenylethyl acetate also occurred. The kinetic results revealed that ethylbenzene formation was enhancedwith higher amounts of PdZn/Al2O3, whereas lipase did not catalyze ethylbenzene formation. Furthermore, ethylbenzene was formed in the hydrogenolysis of (R, S)phenylethanol and in the debenzylation of (R, S)1phenylethylacetate over Pd/Al2O3 catalyst. The presence of Ru/Al2O3 catalyst, in which Ru was in the oxidation state of 3+, enhanced the formation of R1phenylethyl acetate, although no clear racemization of S1phenylethanol during the onepot synthesis of R1phenylethyl acetate was observed. Dynamic kinetic resolution of (R, S)1phenylethanol in toluene, was, however, demonstrated over Ru/Al2O3 and lipase.
|
|
| 5. |
- Leyton, A., et al.
(author)
-
Identification and efficient extraction method of phlorotannins from the brown seaweed Macrocystis pyrifera using an orthogonal experimental design
- 2016
-
In: Algal Research. - : Elsevier. - 2211-9264. ; 16, s. 201-208
-
Journal article (peer-reviewed)abstract
- Abstract The brown seaweed contains a type polyphenol compound characteristic of its species, the phlorotannins, which are produced from the polymerization of phloroglucinol units. They have been extensively studied due to their pharmacological and nutraceutical properties, but there is still a need for an optimized extraction protocol. In this study, the brown seaweed Macrocystis pyrifera was employed to determine the best conditions for extraction of phlorotannins. A set of different variables were evaluated such as the use of pre-treatment, type of solvent, drying temperature, particle size, temperature and extraction time as well as the solid/liquid ratio upon extraction. The optimal conditions for the extraction of phlorotannins were: pre-treatment with hexane, extraction with water, drying temperature 40 °C, particle size below 1.4 mm, at 55 °C for 4 h and a solid-to-liquid ratio of 1:15. Under these conditions, the concentration of phlorotannins achieved in the extract was 200.5 ± 5.6 mg gallic acid equivalent (GAE)/100 g dry seaweed (DS) and total antioxidant activity of the extract of 38.4 ± 2.9 mg trolox equivalent (TE)/100 g DS. Further, it was possible to identify two phlorotannins through HPLC-ESI-MS analyses: phloroeckol and a tetrameric phloroglucinol. These phlorotannins have been reported in the literature to have an antidiabetic effect and prevention of Alzheimer's disease for phloroeckol, and free radical scavenging ability and antiallergic effect for tetrameric phloroglucinol. Therefore, the extract of phlorotannins has potential as medicinal foods or therapeutics for human health applications.
|
|
| 6. |
|
|
| 7. |
- Kirilin, A, et al.
(author)
-
Chemo-Bio Catalyzed Synthesis of R-1-Phenylethyl Acetate over Bimetallic PdZn Catalysts, Lipase, and Ru/Al2O3 : part II
- 2011
-
In: Kinetics and catalysis. - : Maik Nauka/Interperiodica. - 0023-1584 .- 1608-3210. ; 52:1, s. 77-81
-
Journal article (peer-reviewed)abstract
- One-pot synthesis of R-1-phenyethylacetate at 70 degrees C was investigated using three different catalysts simultaneously, namely a bimetallic PdZn/Al2O3 as a hydrogenation catalyst, an immobilized lipase as an acylation catalyst and Ru/Al2O3 as a racemization catalyst. The most active bimetallic catalyst was PdZn/Al2O3 calcined at 300 degrees C and reduced at 400 degrees C, whereas the most selective although less active catalyst was the one being calcined and reduced at 500 degrees C. The highest selectivity to R-1-phenylethyl acetate over this catalyst was 32 at 48% conversion. Ru/Al2O3 was confirmed to have a positive effect on the formation of the desired product, although it was not very active in the racemization during one-pot synthesis.
|
|
| 8. |
- Kirilin, A, et al.
(author)
-
Chemo-bio catalyzed synthesis of R-1-phenylethyl acetateover bimetallic PdZn catalysts, lipase and Ru/Al2o3. Part I
- 2011
-
In: Kinetics and catalysis. - Moskva : Nauka. - 0023-1584 .- 1608-3210. ; 52:1, s. 78-82
-
Journal article (peer-reviewed)abstract
- The effect of calcination and reduction temperature on the physical properties of PdZn/Al2O3 catalysts, prepared by coprecipitation deposition technique and characterized by XPS, XRD and TEM methods are reported. The temperatures were varied in a range of 300–500°C. The catalyst calcined at 300°C and reducedat 400°C exhibited the metal particle size of 2–6 nm and contained the highest surface concentrations of Pd and Zn according to XPS measurements. The size and the fraction of large particles (above 10 nm) increased with increasing the calcinations and reduction temperatures.
|
|
| 9. |
- Hendrickx, Jan-Jaap, et al.
(author)
-
Familial aggregation of tinnitus : a European multicentre study
- 2007
-
In: B-ENT. - Louvain, Belgium : Societe Royale Belge d'Oto - Rhino - Laryngologie et de Chirurgie Cervico - Faciale. - 0001-6497. ; 3:Suppl 7, s. 51-60
-
Journal article (other academic/artistic)abstract
- INTRODUCTION AND AIM:Tinnitus is a common condition affecting approximately 20% of the older population. There is increasing evidence that changes in the central auditory system following cochlear malfunctioning are responsible for tinnitus. To date, few investigators have studied the influence of genetic factors on tinnitus. The present report investigates the presence of a familial effect in tinnitus subjects.METHODS:In a European multicentre study, 198 families were recruited in seven European countries. Each family had at least 3 siblings. Subjects were screened for causes of hearing loss other than presbyacusis by clinical examination and a questionnaire. The presence of tinnitus was evaluated with the question "Nowadays, do you ever get noises in your head or ear (tinnitus) which usually last longer than five minutes". Familial aggregation was tested using three methods: a mixed model approach, calculating familial correlations, and estimating the risk of a subject having tinnitus if the disorder is present in another family member.RESULTS:All methods demonstrated a significant familial effect for tinnitus. The effect persisted after correction for the effect of other risk factors such as hearing loss, gender and age. The size of the familial effect is smaller than that for age-related hearing impairment, with a familial correlation of 0.15.CONCLUSION:The presence of a familial effect for tinnitus opens the door to specific studies that can determine whether this effect is due to a shared familial environment or the involvement of genetic factors. Subsequent association studies may result in the identification of the factors responsible. In addition, more emphasis should be placed on the effect of role models in the treatment of tinnitus.
|
|
| 10. |
- Huyghe, Jeroen R., et al.
(author)
-
Genome-wide SNP analysis reveals no gain in power for association studies of common variants in the Finnish Saami
- 2010
-
In: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 18:5, s. 569-574
-
Journal article (peer-reviewed)abstract
- The Saami from Fennoscandia are believed to represent an ancient, genetically isolated population with no evidence of population expansion. Theoretical work has indicated that under this demographic scenario, extensive linkage disequilibrium (LD) is generated by genetic drift. Therefore, it has been suggested that the Saami would be particularly suited for genetic association studies, offering a substantial power advantage and allowing more economic study designs. However, no study has yet assessed this claim. As part of a GWAS for a complex trait, we evaluated the relative power for association studies of common variants in the Finnish Saami. LD patterns in the Saami were very similar to those in the non-African HapMap reference panels. Haplotype diversity was reduced and, on average, levels of LD were higher in the Saami as compared with those in the HapMap panels. However, using a 'hidden' SNP approach we show that this does not translate into a power gain in association studies. Contrary to earlier claims, we show that for a given set of common SNPs, genomic coverage attained in the Saami is similar to that in the non-African HapMap panels. Nevertheless, the reduced haplotype diversity could potentially facilitate gene identification, especially if multiple rare variants play a role in disease etiology. Our results further indicate that the HapMap is a useful resource for genetic studies in the Saami.
|
|
