| 21. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 22. |
- Feitosa, Mary F., et al.
(författare)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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| 23. |
- Gao, Yumeng, et al.
(författare)
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Tailoring Self-Assembly of Alternating Copolymers for Ordered and Crystalline 2D Nanostructures via Diverse Strategies
- 2024
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Ingår i: Macromolecules. - 0024-9297 .- 1520-5835. ; 57:12, s. 5656-5665
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Tidskriftsartikel (refereegranskat)abstract
- The pursuit of ordered two-dimensional (2D) materials with customized properties has fueled extensive research. While many established fabrication methods rely on substrates, solution-based polymer self-assembly processes remain much unexplored. Here, by manipulating the delicate balance between dominating and competing forces, we demonstrate how polymer chains fold, self-adjust, and self-assemble into diverse ordered 2D nanostructures in solution guided by an energy landscape, especially highly ordered crystalline structures, which are of great challenge to realize by polymers. An alternating copolymer initially self-assembled into 2D planar flakes via a kinetic pathway, lacking crystallinity. Through thermal annealing, they overcame a local kinetic barrier, in situ transforming into 2D circular crystalline clusters. Furthermore, by facilely replacing alkenyl linkers with triazoles in the alternating copolymers, additional tunable competing interactions were introduced, enabling the system to take thermodynamically favored pathways from the beginning and form 2D crystalline spindles directly. Besides, both the systems exhibited reversible self-assembly behavior and remote-controllable merit under light irradiation, forming 2D crystalline structures including flowers and spindles, respectively, highlighting the systems’ responsiveness and versatility. This study offers diverse and facile strategies for constructing and fine-tuning tailorable nanostructures, suggesting promising applications in precision engineering and biomedical technologies.
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| 24. |
- Gustafsson, Mikaela, et al.
(författare)
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A Family of Flexible Lanthanide Bipyridinedicarboxylate Metal-Organic Frameworks Showing Reversible Single-Crystal to Single-Crystal Transformations
- 2012
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 12:6, s. 3243-3249
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Tidskriftsartikel (refereegranskat)abstract
- A family of flexible lanthanide metal-organic frameworks, [Ln(2)(bpydc)(3)(H2O)(3)]center dot nDMF (denoted as SUMOF-6-Ln; Ln = Nd, Sm, Eu, Gd, Tb, Dy, Ho, and Er, H(2)bpydc =2,2'-bipyridine-5,5'-dicarboxylic acid), was synthesized and characterized. SUMOF-6-Ln has a monoclinic space group P2(1)/c. The three-dimensional framework contains chains of LnO(n) (n = 7-8) polyhedra connected through the bpydc linkers forming 1D rhombic channels along the c-axis. SUMOF-6-Ln showed reversible breathing phenomenon upon desorption/adsorption of the solvent, with up to 27% changes of the unit cell dimensions and 23% changes of the unit cell volume. Single crystal X-ray diffraction (XRD) revealed that the desolvation and resolvation of SUMOF-6-Ln occurred via single-crystal to single-crystal transformations. The thermal behavior of SUMOF-6-Sm was also examined. SUMOF-6-Eu and SUMOF-6-Tb showed solid-state luminescent properties.
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| 25. |
- Han, Shengyi, et al.
(författare)
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Probiotic Gastrointestinal Transit and Colonization After Oral Administration : A Long Journey
- 2021
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Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 11
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Forskningsöversikt (refereegranskat)abstract
- Orally administered probiotics encounter various challenges on their journey through the mouth, stomach, intestine and colon. The health benefits of probiotics are diminished mainly due to the substantial reduction of viable probiotic bacteria under the harsh conditions in the gastrointestinal tract and the colonization resistance caused by commensal bacteria. In this review, we illustrate the factors affecting probiotic viability and their mucoadhesive properties through their journey in the gastrointestinal tract, including a discussion on various mucosadhesion-related proteins on the probiotic cell surface which facilitate colonization.
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| 26. |
- Hu, Liangbing, et al.
(författare)
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Transparent and conductive paper from nanocellulose fibers
- 2013
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Ingår i: Energy & Environmental Science. - 1754-5692 .- 1754-5706. ; 6:2, s. 513-518
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Tidskriftsartikel (refereegranskat)abstract
- Here we report on a novel substrate, nanopaper, made of cellulose nanofibrils, an earth abundant material. Compared with regular paper substrates, nanopaper shows superior optical properties. We have carried out the first study on the optical properties of nanopaper substrates. Since the size of the nanofibrils is much less than the wavelength of visible light, nanopaper is highly transparent with large light scattering in the forward direction. Successful depositions of transparent and conductive materials including tin-doped indium oxide, carbon nanotubes and silver nanowires have been achieved on nanopaper substrates, opening up a wide range of applications in optoelectronics such as displays, touch screens and interactive paper. We have also successfully demonstrated an organic solar cell on the novel substrate.
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| 27. |
- Huang, Shan, et al.
(författare)
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Dipyridamole enhances the anti-cancer ability of aspirin against colorectal cancer by inducing apoptosis in an unfolded protein response-dependent manner
- 2023
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Ingår i: Cellular Oncology. - : Springer Science and Business Media LLC. - 2211-3428 .- 2211-3436. ; 46:4, s. 953-967
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Available evidence indicates that dipyridamole enhances the anti-thrombotic effects of aspirin for the prevention of secondary strokes. Aspirin is a well-known non-steroid anti-inflammatory drug. This anti-inflammatory property has turned aspirin into a potential drug for inflammation-related cancers such as colorectal cancer (CRC). Here, we aimed to explore whether the anti-cancer effect of aspirin against CRC could be improved by combined administration with dipyridamole.METHODS: Population-based clinical data analysis was conducted to assess a possible therapeutic effect of combined dipyridamole and aspirin treatment in inhibiting CRC compared with either monotherapy. This therapeutic effect was further verified in different CRC mouse models, i.e. an orthotopic xenograft mouse model, an AOM/DSS mouse model, an Apc min/+ mouse model and a patient derived xenograft (PDX) mouse model. The in vitro effects of the drugs on CRC cells were tested using CCK8 and flow cytometry assays. RNA-Seq, Western blotting, qRT-PCR and flow cytometry were used to identify the underlying molecular mechanisms. RESULTS: We found that dipyridamole combined with aspirin had a better inhibitory effect on CRC than either monotherapy alone. The enhanced anti-cancer effect of the combined use of dipyridamole with aspirin was found to rely on the induction of an overwhelmed endoplasmic reticulum (ER) stress and subsequent pro-apoptotic unfolded protein response (UPR), which was different from the anti-platelet effect.CONCLUSIONS: Our data indicate that the anti-cancer effect of aspirin against CRC may be enhanced by combined administration with dipyridamole. In case further clinical studies confirm our findings, these may be repurposed as adjuvant agents.
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| 28. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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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.
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| 29. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 30. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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