| 1. |
- Mishra, A., et al.
(författare)
-
Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
-
Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Silventoinen, K., et al.
(författare)
-
Differences in genetic and environmental variation in adult BMI by sex, age, time period, and region : An individual-based pooled analysis of 40 twin cohorts
- 2017
-
Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 106:2, s. 457-466
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m2)], but factors modifying these variance components are poorly understood.Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity.Design: We used genetic structural equation modeling to analyze BMI in twins ≥20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs).Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20-29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI.Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population.
|
|
| 5. |
- Joshi, Peter K, et al.
(författare)
-
Directional dominance on stature and cognition in diverse human populations
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
-
Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
|
|
| 6. |
- Chen, Zhishan, et al.
(författare)
-
Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
|
|
| 7. |
- Qi, Qibin, et al.
(författare)
-
FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
-
Tidskriftsartikel (refereegranskat)abstract
- FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
|
|
| 8. |
- Yan, C., et al.
(författare)
-
Size-dependent influence of NOx on the growth rates of organic aerosol particles
- 2020
-
Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:22
-
Tidskriftsartikel (refereegranskat)abstract
- Atmospheric new-particle formation (NPF) affects climate by contributing to a large fraction of the cloud condensation nuclei (CCN). Highly oxygenated organic molecules (HOMs) drive the early particle growth and therefore substantially influence the survival of newly formed particles to CCN. Nitrogen oxide (NOx) is known to suppress the NPF driven by HOMs, but the underlying mechanism remains largely unclear. Here, we examine the response of particle growth to the changes of HOM formation caused by NOx. We show that NOx suppresses particle growth in general, but the suppression is rather nonuniform and size dependent, which can be quantitatively explained by the shifted HOM volatility after adding NOx. By illustrating how NOx affects the early growth of new particles, a critical step of CCN formation, our results help provide a refined assessment of the potential climatic effects caused by the diverse changes of NOx level in forest regions around the globe.
|
|
| 9. |
- Heid, Iris M, et al.
(författare)
-
Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
-
Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
|
|
| 10. |
- Kim, J., et al.
(författare)
-
Hygroscopicity of nanoparticles produced from homogeneous nucleation in the CLOUD experiments
- 2016
-
Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 16:1, s. 293-304
-
Tidskriftsartikel (refereegranskat)abstract
- Sulfuric acid, amines and oxidized organics have been found to be important compounds in the nucleation and initial growth of atmospheric particles. Because of the challenges involved in determining the chemical composition of objects with very small mass, however, the properties of the freshly nucleated particles and the detailed pathways of their formation processes are still not clear. In this study,we focus on a challenging size range, i.e., particles that have grown to diameters of 10 and 15 nm following nucleation, and measure their water uptake. Water uptake is useful information for indirectly obtaining chemical composition of aerosol particles. We use a nanometer-hygroscopicity tandem differential mobility analyzer (nano-HTDMA) at sub-saturated conditions (ca. 90% relative humidity at 293 K) to measure the hygroscopicity of particles during the seventh Cosmics Leaving OUtdoor Droplets (CLOUD7) campaign performed at CERN in 2012. In CLOUD7, the hygroscopicity of nucleated nanoparticles was measured in the presence of sulfuric acid, sulfuric acid-dimethylamine, and sulfuric acid-organics derived from alpha-pinene oxidation. The hygroscopicity parameter kappa decreased with increasing particle size, indicating decreasing acidity of particles. No clear effect of the sulfuric acid concentration on the hygroscopicity of 10 nm particles produced from sulfuric acid and dimethylamine was observed, whereas the hygroscopicity of 15 nm particles sharply decreased with decreasing sulfuric acid concentrations. In particular, when the concentration of sulfuric acid was 5.1 x 10(6) molecules cm(-3) in the gas phase, and the dimethylamine mixing ratio was 11.8 ppt, the measured kappa of 15 nm particles was 0.31 +/- 0.01: close to the value reported for dimethylaminium sulfate (DMAS) (kappa(DMAS) similar to 0.28). Furthermore, the difference in kappa between sulfuric acid and sulfuric acid-dimethylamine experiments increased with increasing particle size. The kappa values of particles in the presence of sulfuric acid and organics were much smaller than those of particles in the presence of sulfuric acid and dimethylamine. This suggests that the organics produced from alpha-pinene ozonolysis play a significant role in particle growth even at 10 nm sizes.
|
|
| 11. |
- Speliotes, Elizabeth K., et al.
(författare)
-
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
|
|
| 12. |
- Albrecht, Eva, et al.
(författare)
-
Telomere length in circulating leukocytes is associated with lung function and disease
- 2014
-
Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 43:4, s. 983-992
-
Tidskriftsartikel (refereegranskat)abstract
- Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in is (FEV1), forced vital capacity (PVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (beta= -0.0452, p= 0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07 x 10(-7)), FVC (p=2.07 x 10(-5)), and FEV1/FVC (p =5.27 x 10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.
|
|
| 13. |
- Gates, J. M., et al.
(författare)
-
Decay Spectroscopy of Element 115 Daughters: 280Rg -> 276Mt and 276Mt -> 272Bh
- 2015
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:2
-
Tidskriftsartikel (refereegranskat)abstract
- Forty-six decay chains, assigned to the decay of 288-115, were produced using the 243Am(48Ca,3n)288-115 reaction at the Lawrence Berkeley National Laboratory 88-in. cyclotron. The resulting series of α decays were studied using α-photon and α-x-ray spectroscopies. Multiple α-photon coincidences were observed in the element 115 decay chain members, particularly in the third- and fourth-generation decays (presumed to be 280Rg and 276Mt, respectively). Upon combining these data with those from 22 288-115 decay chains observed in a similar experiment, updated level schemes in 276Mt and 272Bh (populated by the α decay of 280Rg and 276Mt, respectively) are proposed. Photons were observed in the energy range expected for K x rays coincident with the α decay of both 280Rg and 276Mt. However, Compton scattering of higher-energy γ rays and discrete transitions are present in the K x-ray region preventing a definitive Z identification to be made based on observation of characteristic K x-ray energies.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Kolhinen, V. S., et al.
(författare)
-
Recommissioning of JYFLTRAP at the new IGISOL-4 facility
- 2013
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier BV. - 0168-583X .- 1872-9584. ; 317:Part B, s. 506-509
-
Tidskriftsartikel (refereegranskat)abstract
- The JYFLTRAP double Penning-trap system was moved to a new location along with the Ion Guide Isotope Separator On-line (IGISOL) facility at the Accelerator Laboratory of the University of Jyväskylä. The move made it possible to upgrade various parts of the facility. For example, separate beam lines for JYFLTRAP and the collinear laser spectroscopy station were constructed after the radio-frequency quadrupole cooler and buncher. In this contribution we give an overview of the new JYFLTRAP facility and results from the first stable ion-beam tests.
|
|
| 18. |
- Lango Allen, Hana, et al.
(författare)
-
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
-
Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
|
|
| 19. |
|
|
| 20. |
- Naukkarinen, J., et al.
(författare)
-
Characterising metabolically healthy obesity in weight-discordant monozygotic twins
- 2014
-
Ingår i: Diabetologia. - New York, USA : Springer. - 0012-186X .- 1432-0428. ; 57:1, s. 167-176
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Not all obese individuals display the metabolic disturbances commonly associated with excess fat accumulation. Mechanisms maintaining this ‘metabolically healthy obesity’ (MHO) are as yet unknown. We aimed to study different fat depots and transcriptional pathways in subcutaneous adipose tissue (SAT) as related to the MHO phenomenon.Methods: Sixteen rare young adult obesity-discordant monozygotic (MZ) twin pairs (intra-pair difference (∆) in BMI ≥3 kg/m2), aged 22.8–35.8 years, were examined for detailed characteristics of metabolic health (subcutaneous, intra-abdominal and liver fat [magnetic resonance imaging/spectroscopy]), OGTT, lipids, adipokines and C-reactive protein (CRP). Affymetrix U133 Plus 2.0 chips were used to analyse transcriptomics pathways related to mitochondrial function and inflammation in SAT.Results: Based on liver fat accumulation, two metabolically different subgroups emerged. In half (8/16) of the pairs (∆weight 17.1 ± 2.0 kg), the obese co-twin had significantly higher liver fat (∆718%), 78% increase in AUC insulin during OGTT and CRP, significantly more disturbance in the lipid profile and greater tendency for hypertension compared with the lean co-twin. In these obese co-twins, SAT expression of mitochondrial oxidative phosphorylation, branched-chain amino acid catabolism, fatty acid oxidation and adipocyte differentiation pathways were downregulated and chronic inflammation upregulated. In the other eight pairs (∆weight 17.4 ± 2.8 kg), the obese co-twin did not differ from the non-obese co-twin in liver fat (∆8%), insulin sensitivity, CRP, lipids, blood pressure or SAT transcriptomics.Conclusions/interpretation: Our results suggest that maintenance of high mitochondrial transcription and lack of inflammation in SAT are associated with low liver fat and MHO.
|
|
| 21. |
|
|
| 22. |
- Orava, J., et al.
(författare)
-
Blunted Metabolic Responses to Cold and Insulin Stimulation in Brown Adipose Tissue of Obese Humans
- 2013
-
Ingår i: Obesity. - : Wiley. - 1930-7381. ; 21:11, s. 2279-2287
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Inactive brown adipose tissue (BAT) may predispose to weight gain. This study was designed to measure metabolism in the BAT of obese humans, and to compare it to that in lean subjects. The impact of weight loss on BAT and the association of detectable BAT with various metabolic characteristics were also assessed. Design and Methods: Using positron emission tomography (PET), cold-and insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean humans were quantified. Further, cold-induced glucose uptake was measured in obese subjects before and after a 5-month conventional weight loss. Results: Mean responses in BAT glucose uptake rate to both cold and insulin stimulation were twice as large in lean as in obese subjects. Blood flow in BAT was also lower in obese subjects under cold conditions. The increase in cold-induced BAT glucose uptake rate after weight loss was not statistically significant. Subjects with cold-activated detectable BAT were leaner and had higher whole-body insulin sensitivity than BAT-negative subjects, irrespective of age and gender. Conclusions: The effects of cold and insulin on BAT activity are severely blunted in obesity, and the presence of detectable BAT may contribute to a metabolically healthy status.
|
|
| 23. |
- Rönö, K., et al.
(författare)
-
The neurodevelopmental morbidity of children born after assisted reproductive technology: a Nordic register study from the Committee of Nordic Assisted Reproductive Technology and Safety group
- 2022
-
Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 117:5, s. 1026-1037
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the risk of neurodevelopmental disorders in singletons born after the use of assisted reproductive technology (ART) compared with singletons born without the use of ART. Design: Nordic register-based study. Setting: Cross-linked data from Medical Birth Registers and National ART and Patient Registers; liveborn singletons in 1995–2014 in Denmark and Finland, 2005–2015 in Norway, and 1995–2015 in Sweden with follow-up to 2014 (Denmark and Finland) or 2015 (Norway and Sweden). Patients: A total of 5,076,444 singletons: 116,909 (2.3%) born with and 4,959,535 (97.7%) born without the use of ART (non-ART). Interventions: In vitro fertilization, intracytoplasmic sperm injection, and fresh and frozen embryo transfer. Main Outcome Measures: The primary outcomes (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes) were learning and motor functioning disorders (F80–F83), autism spectrum disorder (F84), attention-deficit/hyperactivity disorder and conduct disorders (F90–F92), and tic disorders (F95). Crude hazard ratios (HRs) and adjusted hazard ratios (aHRs) with 95% confidence intervals were calculated. Results: Singletons in the ART cohort had a higher adjusted risk of learning and motor functioning disorders (HR, 1.01 [0.96–1.07]; aHR, 1.17 [1.11–1.24]) and a tendency toward a higher risk of autism spectrum disorder (HR, 1.12 [1.04–1.21]; aHR, 1.07 [0.98–1.16]) and attention-deficit/hyperactivity disorder and conduct disorders (HR, 0.82 [0.77–0.86]; aHR, 1.17 [0.99–1.12]) but not of tic disorders (HR, 1.21 [1.06–1.38]; aHR, 1.17 [0.96–1.27]). No differences in risk were found between children born after in vitro fertilization and intracytoplasmic sperm injection or after fresh and frozen embryo transfer. Conclusions: Our findings of only small differences in neurodevelopment between ART and non-ART singletons are reassuring and in line with previous studies. © 2022 American Society for Reproductive Medicine
|
|
| 24. |
- Sevastianova, K., et al.
(författare)
-
Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans
- 2012
-
Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 96:4, s. 727-734
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cross-sectional studies have identified a high intake of simple sugars as an important dietary factor predicting nonalcoholic fatty liver disease (NAFLD). Objective: We examined whether overfeeding overweight subjects with simple sugars increases liver fat and de novo lipogenesis (DNL) and whether this is reversible by weight loss. Design: Sixteen subjects [BMI (kg/m(2)): 30.6 +/- 1.2] were placed on a hypercaloric diet (>1000 kcal simple carbohydrates/d) for 3 wk and, thereafter, on a hypocaloric diet for 6 mo. The subjects were genotyped for rs739409 in the PNPLA3 gene. Before and after overfeeding and after hypocaloric diet, metabolic variables and liver fat (measured by proton magnetic resonance spectroscopy) were measured. The ratio of palmitate (16:0) to linoleate (18:2n-6) in serum and VLDL triglycerides was used as an index of DNL. Results: Carbohydrate overfeeding increased weight (+/- SEM) by 2% (1.8 +/- 0.3 kg; P < 0.0001) and liver fat by 27% from 9.2 +/- 1.9% to 11.7 +/- 1.9% (P = 0.005). DNL increased in proportion to the increase in liver fat and serum triglycerides in subjects with PNPLA3-148II but not PNPLA3-148MM. During the hypocaloric diet, the subjects lost 4% of their weight (3.2 +/- 0.6 kg; P < 0.0001) and 25% of their liver fat content (from 11.7 +/- 1.9% to 8.8 +/- 1.8%; P < 0.05). Conclusions: Carbohydrate overfeeding for 3 wk induced a >10-fold greater relative change in liver fat (27%) than in body weight (2%). The increase in liver fat was proportional to that in DNL. Weight loss restores liver fat to normal. These data indicate that the human fatty liver avidly accumulates fat during carbohydrate overfeeding and support a role for DNL in the pathogenesis of NAFLD. This trial was registered at www.hus.fi as 235780. Am J Clin Nutr 2012;96:727-34.
|
|
| 25. |
|
|
| 26. |
- Suviolahti, E, et al.
(författare)
-
The SLC6A14 gene shows evidence of association with obesity
- 2003
-
Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 112:11, s. 1762-1772
-
Tidskriftsartikel (refereegranskat)abstract
- In our previous genome-wide scan of Finnish nuclear families, obesity was linked to chromosome Xq24. Here we analyzed this 15-Mb region by genotyping 9 microsatellite markers and 36 single nucleotide polyp morphisms (SNPs) for 11 positional and functional candidate genes in an extended sample of 218 obese Finnish sibling pairs (sibpairs) (BMI > 30 kg/m(2)). Evidence of linkage emerged mainly from the obese male sibpairs, suggesting a gender-specific effect for the underlying gene. By constructing haplotypes among the obese male sibpairs, we restricted the region from 15 Mb to 4 Mb, between markers DXS8088 and DXS8067. Regional functional candidate genes were tested for association in an initial sample of 117 cases and 182 controls. Significant evidence was observed for association for an SNP in the 3'-untranslated region of the solute carrier family 6 member 14 (SLC6A14) gene (P = 0.0002) and for SNP haplotypes of the SLC6A14 gene (P = 0.0007-0.006). Furthermore, an independent replication study sample of 837 cases and 968 controls from Finland and Sweden also showed significant differences in allele frequencies between obese and non-obese individuals (P = 0.003). The SLC6A14 gene is an interesting novel candidate for obesity because it encodes an amino acid transporter, which potentially regulates tryptophan availability for serotonin synthesis and thus possibly affects appetite control.
|
|
| 27. |
|
|
| 28. |
- Watts, Eleanor L., et al.
(författare)
-
Circulating free testosterone and risk of aggressive prostate cancer : Prospective and Mendelian randomisation analyses in international consortia
- 2022
-
Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 151:7, s. 1033-1046
-
Tidskriftsartikel (refereegranskat)abstract
- Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet =.0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.
|
|
| 29. |
- Abdissa, Negera, et al.
(författare)
-
Naphthalene Derivatives from the Roots of Pentas parvifolia and Pentas bussei
- 2016
-
Ingår i: Journal of natural products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 79:9, s. 2181-2187
-
Tidskriftsartikel (refereegranskat)abstract
- The phytochemical investigation of the CH2Cl2/MeOH (1:1) extract of the roots of Pentas parvifolia led to the isolation of three new naphthalenes, parvinaphthols A (1), B (2), and C (3), two known anthraquinones, and five known naphthalene derivatives. Similar investigation of the roots of Pentas bussei afforded a new polycyclic naphthalene, busseihydroquinone E (4), a new 2,2′-binaphthralenyl-1,1′-dione, busseihydroquinone F (5), and five known naphthalenes. All purified metabolites were characterized by NMR and MS data analyses, whereas the absolute configurations of 3 and 4 were determined by single-crystal X-ray diffraction studies. The E-geometry of compound 5 was supported by DFT-based chemical shift calculations. Compounds 2-4 showed marginal cytotoxicity against the MDA-MB-231 human triple-negative breast cancer cell line with IC50 values ranging from 62.3 to 129.6 μM. © 2016 The American Chemical Society and American Society of Pharmacognosy.
|
|
| 30. |
- Ahlm, Lars, et al.
(författare)
-
Modeling the thermodynamics and kinetics of sulfuric acid-dimethylamine-water nanoparticle growth in the CLOUD chamber
- 2016
-
Ingår i: Aerosol Science and Technology. - : Informa UK Limited. - 0278-6826 .- 1521-7388. ; 50:10, s. 1017-1032
-
Tidskriftsartikel (refereegranskat)abstract
- Dimethylamine (DMA) has a stabilizing effect on sulfuric acid (SA) clusters, and the SA and DMA molecules and clusters likely play important roles in both aerosol particle formation and growth in the atmosphere. We use the monodisperse particle growth model for acid-base chemistry in nanoparticle growth (MABNAG) together with direct and indirect observations from the CLOUD4 and CLOUD7 experiments in the cosmics leaving outdoor droplets (CLOUD) chamber at CERN to investigate the size and composition evolution of freshly formed particles consisting of SA, DMA, and water as they grow to 20nm in dry diameter. Hygroscopic growth factors are measured using a nano-hygroscopicity tandem differential mobility analyzer (nano-HTDMA), which combined with simulations of particle water uptake using the thermodynamic extended-aerosol inorganics model (E-AIM) constrain the chemical composition. MABNAG predicts a particle-phase ratio between DMA and SA molecules of 1.1-1.3 for a 2nm particle and DMA gas-phase mixing ratios between 3.5 and 80 pptv. These ratios agree well with observations by an atmospheric-pressure interface time-of-flight (APi-TOF) mass spectrometer. Simulations with MABNAG, direct observations of the composition of clusters <2nm, and indirect observations of the particle composition indicate that the acidity of the nucleated particles decreases as they grow from approximate to 1 to 20nm. However, MABNAG predicts less acidic particles than suggested by the indirect estimates at 10nm diameter using the nano-HTDMA measurements, and less acidic particles than observed by a thermal desorption chemical ionization mass spectrometer (TDCIMS) at 10-30nm. Possible explanations for these discrepancies are discussed.
|
|
| 31. |
- Almeida, Joao, et al.
(författare)
-
Molecular understanding of sulphuric acid-amine particle nucleation in the atmosphere
- 2013
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 502:7471, s. 359-
-
Tidskriftsartikel (refereegranskat)abstract
- Nucleation of aerosol particles from trace atmospheric vapours is thought to provide up to half of global cloud condensation nuclei(1). Aerosols can cause a net cooling of climate by scattering sunlight and by leading to smaller but more numerous cloud droplets, which makes clouds brighter and extends their lifetimes(2). Atmospheric aerosols derived from human activities are thought to have compensated for a large fraction of the warming caused by greenhouse gases(2). However, despite its importance for climate, atmospheric nucleation is poorly understood. Recently, it has been shown that sulphuric acid and ammonia cannot explain particle formation rates observed in the lower atmosphere(3). It is thought that amines may enhance nucleation(4-16), but until now there has been no direct evidence for amine ternary nucleation under atmospheric conditions. Here we use the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN and find that dimethylamine above three parts per trillion by volume can enhance particle formation rates more than 1,000-fold compared with ammonia, sufficient to account for the particle formation rates observed in the atmosphere. Molecular analysis of the clusters reveals that the faster nucleation is explained by a base-stabilization mechanism involving acid-amine pairs, which strongly decrease evaporation. The ion-induced contribution is generally small, reflecting the high stability of sulphuric acid-dimethylamine clusters and indicating that galactic cosmic rays exert only a small influence on their formation, except at low overall formation rates. Our experimental measurements are well reproduced by a dynamical model based on quantum chemical calculations of binding energies of molecular clusters, without any fitted parameters. These results show that, in regions of the atmosphere near amine sources, both amines and sulphur dioxide should be considered when assessing the impact of anthropogenic activities on particle formation.
|
|
| 32. |
- Atilaw, Yoseph, et al.
(författare)
-
Prenylated Flavonoids from the Roots of Tephrosia rhodesica
- 2020
-
Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 83:8, s. 2390-2398
-
Tidskriftsartikel (refereegranskat)abstract
- Five new compounds-rhodimer (1), rhodiflavan A (2), rhodiflavan B (3), rhodiflavan C (4), and rhodacarpin (5)-along with 16 known secondary metabolites, were isolated from the CH2Cl2-CH3OH (1:1) extract of the roots of Tephrosia rhodesica. They were identified by NMR spectroscopic, mass spectrometric, X-ray crystallographic, and ECD spectroscopic analyses. The crude extract and the isolated compounds 2-5, 9, 15, and 21 showed activity (100% at 10 mu g and IC50 = 5-15 mu M) against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum.
|
|
| 33. |
|
|
| 34. |
- Brönnimann, D., et al.
(författare)
-
The lay of land: Strontium isotope variability in the dietary catchment of the Late Iron Age proto-urban settlement of Basel-Gasfabrik, Switzerland
- 2018
-
Ingår i: Journal of Archaeological Science: Reports. - : Elsevier BV. - 2352-409X. ; 17, s. 279-292
-
Tidskriftsartikel (refereegranskat)abstract
- Basel-Gasfabrik (Switzerland) comprises an extensive La Tène (chiefly Lt D, 150–80 BCE) settlement and two associated cemeteries at which strontium (87Sr/86Sr) isotope analysis of human and animal teeth investigated regional and supra-regional contacts. The interpretation of the analytic data, however, requires information on the isotopic baseline values around the site. Using 102 modern vegetation and 9 water samples from 51 localities, this study characterizes the isotopic ratios of the biologically available strontium of geological units and watercourses around Basel and compares these to 28 human infant, 6 pig, and 5 dog teeth from the site. Furthermore, pedological criteria evaluate the suitability of landforms for crop and pasturelands. The 87Sr/86Sr ratios of the environmental samples from geological units in up to 50 km distance varied between 0.70776 and 0.71794. Human infant teeth exhibited much more homogeneous 87Sr/86Sr ratios (0.70847–0.70950), which coincided largely with those of potential arable soils around Basel and indicate targeted exploitation of landscapes for agriculture. The more variable values of the faunal teeth suggest more widely ranging habitats or imports from the site's hinterlands. Two local isotope ranges were defined based on archaeological enamel samples and modern vegetation data from a confined radius around Basel. The study documents the complexity of distinguishing local and non-local individuals in a geologically heterogeneous region as well as the potential of isotope analyses to explore prehistoric land-use patterns.
|
|
| 35. |
- Deyou, Tsegaye, et al.
(författare)
-
Isoflavones and Rotenoids from the Leaves of Millettia oblata ssp teitensis
- 2017
-
Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 80:7, s. 2060-2066
-
Tidskriftsartikel (refereegranskat)abstract
- A new isoflavone, 8-prenylmilldrone (1), and four new rotenoids, oblarotenoids A-D (2-5), along with nine known compounds (6-14), were isolated from the CH2Cl2/CH3OH (1:1) extract of the leaves of Millettia oblata ssp. teitensis by chromatographic separation. The purified compounds were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of the rotenoids were established on the basis of chiroptical data and in some cases by single-crystal X-ray crystallography. Maximaisoflavone J (11) and oblarotenoid C (4) showed weak activity against the human breast cancer cell line MDA-MB-231 with IC50 values of 33.3 and 93.8 mu M, respectively.
|
|
| 36. |
- Deyou, Tsegaye, et al.
(författare)
-
Rotenoids, Flavonoids, and Chalcones from the Root Bark of Millettia usaramensis
- 2015
-
Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025 .- 0974-5211. ; 78:12, s. 2932-2939
-
Tidskriftsartikel (refereegranskat)abstract
- Five new compounds, 4-O-geranylisoliquiritigenin (1), 12-dihydrousararotenoid B (2), 12-dihydrousararotenoid C (3), 4'-O-geranyl-7-hydroxyflavanone (4), and 4'O-geranyl-7-hydroxydihydroflavanol (5), along with 12 known natural products (6-17) were isolated from the CH2Cl2/MeOH (1:1) extract of the root bark of Millettia usaramensis ssp. usaramensis by chromatographic separation. The purified metabolites were identified by NMR spectroscopic and mass spectrometric analyses, whereas their absolute configurations were established on the basis of chiroptical data and in some cases also by X-ray crystallography. The crude extract was moderately active (IC50 = 11.63 mu g/mL) against the ER-negative MDB-MB-231 human breast cancer cell line, and accordingly compounds 6, 8, 9, 10, 12, and 16 also showed moderate to low cytotoxic activities (IC50 25.7-207.2 mu M). The new natural product 1 exhibited antiplasmodial activity with IC50 values of 3.7 and 5.3 mu M against the chloroquine-sensitive 3D7 and the chloroquine-resistant Dd2 Plasmodium falciparum strains, respectively, and was also cytotoxic to the HEK293 cell line.
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
- Heinonen, S., et al.
(författare)
-
Mitochondria-related transcriptional signature is downregulated in adipocytes in obesity: a study of young healthy MZ twins
- 2017
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 60:1, s. 169-181
-
Tidskriftsartikel (refereegranskat)abstract
- Low mitochondrial activity in adipose tissue is suggested to be an underlying factor in obesity and its metabolic complications. We aimed to find out whether mitochondrial measures are downregulated in obesity also in isolated adipocytes. We studied young adult monozygotic (MZ) twin pairs discordant (n = 14, intrapair difference Delta BMI ae 3 kg/m(2)) and concordant (n = 5, Delta BMI
|
|
| 42. |
|
|
| 43. |
- Johnson, Magnus, et al.
(författare)
-
Neutral Organometallic Halogen Bond Acceptors: Halogen Bonding in Complexes of PCPPdX (X = Cl, Br, I) with Iodine (I(2)), 1,4-Diiodotetrafluorobenzene (F4DIBz), and 1,4-Diiodooctafluorobutane (F8DIBu)
- 2012
-
Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7505 .- 1528-7483. ; 12:1, s. 362-368
-
Tidskriftsartikel (refereegranskat)abstract
- The behavior of a sterically crowded neutral pincer {2,6-bis[(di-t-butylphosphino)methyll-phenyl}palladium (PCPPd) halides, PCPPdX (X = Cl, Br or I), as XB acceptors with strong halogen bond (XB) donors, iodine (I(2)), 1,4-diiodotetrafluorobenzene (F4DIBz), and 1,4-dliodooctafluorobutane (F8DIBu) were studied in the solid state. The co-crystallization experiments afforded high-quality single crystals of XB complexes PCPPdCl-I(2) (1a), PCPPdBr-I(2) (2a), PCPPdI-I(2) (3a), PCPPdCl-F4DD3z (lb), PCPPdBr-F4DIBz (2b), and PCPPdBr-F8DIBu (2c). The 1:1 iodine complexes (la, 2a, and 3a) all showed a strong halogen bonding interaction, the reduction of the sum of the van der Waals radii of halogen to iodine being 24.6 (la), 23.9 (2a), and 19.4% (3a) with X center dot center dot center dot I-I angles of 177, 176, and 179 degrees, respectively. While the pincer palladium chloride 1 and bromide 2 were crystallographically isomorphous and showed similar XB behavior, the palladium iodide complex, 3, exhibited markedly different properties, and unlike 1 and 2 it does not, under similar conditions, result in XB complexes with the weaker XB donors F4DIBz and F8D1Bu. The results indicate that PCPPd1 is not nucleophilic enough to have XB interactions with other donors than iodine. However, the weaker XB donors F4DIBz and F8DIBu form XB complexes with the chloride 1 and especially with the bromide 2. The prevalence of the halogen bonding with 2 is probably not only electronic in origin, and it seems to offer the best balance between electron poorness and steric availability. The X13 interactions with F4DIBz and F8DIBu are much weaker than with iodine, the reduction of the sum of the van der Wash radii of halogen to iodine being 13.5, 12.3, and 14.6% with C-I center dot center dot center dot X angles between 163 and 179 degrees for lb, 2b, and 2c, respectively, and results in polymeric (center dot center dot center dot 1 center dot center dot center dot F4DIBz center dot center dot center dot 1 center dot center dot center dot F4DIBz center dot center dot center dot center dot)(w) (center dot center dot center dot center dot 2 center dot center dot center dot center dot F4DIBz center dot center dot center dot center dot 2 center dot center dot center dot center dot F4DIBz center dot center dot center dot center dot)(w) and (center dot center dot center dot center dot 2 center dot center dot center dot center dot F8DIBu center dot center dot center dot center dot 2 center dot center dot center dot center dot F8DIBu center dot center dot center dot center dot)(N) one-dimensional zigzag chains in the solid state.
|
|
| 44. |
- Kalenga, T. M., et al.
(författare)
-
Modified ent-Abietane Diterpenoids from the Leaves of Suregada zanzibariensis
- 2022
-
Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 85:9, s. 2135-2141
-
Tidskriftsartikel (refereegranskat)abstract
- The leaf extract of Suregada zanzibariensis gave two new modified ent-abietane diterpenoids, zanzibariolides A (1) and B (2), and two known triterpenoids, simiarenol (3) and fi-amyrin (4). The structures of the isolated compounds were elucidated based on NMR and MS data analysis. Single-crystal X-ray diffraction was used to establish the absolute configurations of compounds 1 and 2. The crude leaf extract inhibited the infectivity of herpes simplex virus 2 (HSV-2, IC50 11.5 mu g/mL) and showed toxicity on African green monkey kidney (GMK AH1) cells at CC50 52 mu g/ mL. The isolated compounds 1-3 showed no anti-HSV-2 activity and exhibited insignificant toxicity against GMK AH1 cells at >= 100 mu M.
|
|
| 45. |
|
|
| 46. |
- Karim, A., et al.
(författare)
-
The three-center-four-electron tetrel bond
- 2018
-
Konferensbidrag (refereegranskat)abstract
- We present a thermodynamically stable complex that possesses a three-center-four-electron (3c4e) tetrel bond [1,2], formed by capturing a reactive carbenium ion with a bidentate Lewis base. We report NMR spectroscopic, titration calorimetric and reaction kinetic evidences for the structure of this pentacoordinate species and discuss the properties of its tetrel bond, [N˜˜˜∙∙∙C∙∙∙˜˜˜N]+, in comparison with the analogous halogen, [N˜˜˜∙∙∙X∙∙∙˜˜˜N]+ and hydrogen, [N∙∙∙˜˜˜H∙∙∙˜˜˜N]+, bonds [3]. The necessity of the involvement of a bidentate Lewis base for the formation of a stable 3c4e tetrel bond is demonstrated by providing spectroscopic and crystallographic evidence, that a monodentate Lewis base induces a reaction rather than stabilizing the reactive species. A vastly decreased Lewis basicity of the bidentate ligand or reduced Lewis acidity of the carbenium ion weakens — or even prohibits — the formation of the pentacoordinate species, whereas synthetic modifications facilitating attractive orbital overlaps promote it. As the geometry of the pentacoordinate complex resembles the SN2 transition state, it may provide a model system for the investigation of fundamental reaction mechanisms and chemical bonding theories [4].References1. G.C. Pimentel J. Chem. Phys. 1951, 19, 446-4482. R.H. Crabtree Chem. Soc. Rev. 2017, 46, 1720-1729.3. S.B. Hakkert, M. Erdelyi J. Phys. Org. Chem. 2015, 95, 2572-25784. Karim, N. Schultz, H. Andersson, B. Nekoueishahraki et al, 2018, submitted.
|
|
| 47. |
- Karppi, J., et al.
(författare)
-
Effects of astaxanthin supplementation on lipid peroxidation
- 2007
-
Ingår i: International Journal for Vitamin and Nutrition Research. - : Hogrefe Publishing Group. - 0300-9831 .- 1664-2821. ; 77:1
-
Tidskriftsartikel (refereegranskat)abstract
- Astaxanthin, the main carotenoid pigment in aquatic animals, has greater antioxidant activity in vitro (protecting against lipid peroxidation) and a more polar configuration than other carotenoids. We investigated the effect of three-month astaxanthin supplementation on lipid peroxidation in healthy non-smoking Finnish men, aged 19-33 years by using a randomized double-blind study design. Also absorption of astaxanthin from capsules into bloodstream and its safety were evaluated. The intervention group received two 4-mg astaxanthin (Astaxin®) capsules daily, and the control group two identical-looking placebo capsules. Astaxanthin supplementation elevated plasma astaxanthin levels to 0.032 µmol/L (p < 0.001 for the change compared with the placebo group). We observed that levels of plasma 12- and 15-hydroxy fatty acids were reduced statistically significantly in the astaxanthin group (p = 0.048 and p = 0.047 respectively) during supplementation, but not in the placebo group and the change of 15-hydroxy fatty acid was almost significantly greater (p = 0.056) in the astaxanthin group, as compared with the placebo group. The present study suggests that intestinal absorption of astaxanthin delivered as capsules is adequate, and well tolerated. Supplementation with astaxanthin may decrease in vivo oxidation of fatty acids in healthy men. © Hogrefe & Huber Publishers.
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
- Kirkby, Jasper, et al.
(författare)
-
Ion-induced nucleation of pure biogenic particles
- 2016
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 533:7604, s. 521-526
-
Tidskriftsartikel (refereegranskat)abstract
- Atmospheric aerosols and their effect on clouds are thought to be important for anthropogenic radiative forcing of the climate, yet remain poorly understood(1). Globally, around half of cloud condensation nuclei originate from nucleation of atmospheric vapours(2). It is thought that sulfuric acid is essential to initiate most particle formation in the atmosphere(3,4), and that ions have a relatively minor role(5). Some laboratory studies, however, have reported organic particle formation without the intentional addition of sulfuric acid, although contamination could not be excluded(6,7). Here we present evidence for the formation of aerosol particles from highly oxidized biogenic vapours in the absence of sulfuric acid in a large chamber under atmospheric conditions. The highly oxygenated molecules (HOMs) are produced by ozonolysis of a-pinene. We find that ions from Galactic cosmic rays increase the nucleation rate by one to two orders of magnitude compared with neutral nucleation. Our experimental findings are supported by quantum chemical calculations of the cluster binding energies of representative HOMs. Ion-induced nucleation of pure organic particles constitutes a potentially widespread source of aerosol particles in terrestrial environments with low sulfuric acid pollution.
|
|
