| 11. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 12. |
- 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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| 13. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 14. |
- Reimers, Jeffrey R., et al.
(författare)
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Challenges facing an understanding of the nature of low-energy excited states in photosynthesis
- 2016
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Ingår i: Biochimica et Biophysica Acta - Bioenergetics. - : Elsevier BV. - 0005-2728 .- 1879-2650. ; 1857:9, s. 1627-1640
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Forskningsöversikt (refereegranskat)abstract
- While the majority of the photochemical states and pathways related to the biological capture of solar energy are now well understood and provide paradigms for artificial device design, additional low-energy states have been discovered in many systems with obscure origins and significance. However, as low-energy states are naively expected to be critical to function, these observations pose important challenges. A review of known properties of low energy states covering eight photochemical systems, and options for their interpretation, are presented. A concerted experimental and theoretical research strategy is suggested and outlined, this being aimed at providing a fully comprehensive understanding.
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| 15. |
- Song, Guohe, et al.
(författare)
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TIMP1 is a prognostic marker for the progression and metastasis of colon cancer through FAK-PI3K/AKT and MAPK pathway
- 2016
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Ingår i: Journal of Experimental & Clinical Cancer Research. - London, United Kingdom : BioMed Central (BMC). - 1756-9966. ; 35:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tissue inhibitor matrix metalloproteinase 1 (TIMP1) plays a vital role in carcinogenesis, yet its precise functional roles and regulation remain unclear. In this study, we aim to investigate its biological function and clinical significance in human colon cancer.Methods: We analyzed the expression of TIMP1 in both public database (Oncomine and TCGA) and 94 cases of primary colon cancer and matched normal colon tissue specimens. The underlying mechanisms of altered TIMP1 expression on cell tumorigenesis, proliferation, and metastasis were explored in vitro and in vivo.Results: TIMP1 was overexpressed in colon tumorous tissues and lymph node metastasis specimens than in normal tissues. The aberrant expression of TIMP1 was significantly associated with the regional lymph node metastasis (p = 0.033), distant metastasis (p = 0.039), vascular invasion (p = 0.024) and the American Joint Committee on Cancer (AJCC) stage (p = 0.026). Cox proportional hazards model showed that TIMP1 was an independent prognostic indicator of disease-free survival (HR = 2.603, 95 % CI: 1.115-6.077, p = 0.027) and overall survival (HR = 2.907, 95 % CI: 1.254-6.737, p = 0.013) for patients with colon cancer. Consistent with this, our findings highlight that suppression of TIMP1 expression decreased proliferation, and metastasis but increased apoptosis by inducing TIMP1 specific regulated FAK-PI3K/AKT and MAPK pathway.Conclusion: TIMP1 might play an important role in promoting tumorigenesis and metastasis of human colon cancer and function as a potential prognostic indicator for colon cancer.
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| 16. |
- Wang, Jin, et al.
(författare)
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Conjugated heat transfer analysis of a film cooling passage with turbulator ribs
- 2016
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Ingår i: Heat Transfer Research. - 1064-2285. ; 47:2, s. 89-103
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the adiabatic film cooling effectiveness and conjugate heat transfer characteristics for a circular hole are investigated numerically. Seven turbulator ribs are located on the internal wall, and a film cooling hole between two adjacent ribs has an inclination angle of 30°. The secondary flow rate is affected by the internal channel flow velocity, and the external film cooling is combined with the internal channel flow conditions. In the conjugate heat transfer research, two different plate materials are considered to analyze the heat conduction characteristics. The results show that the turbulator ribs enhance the downstream heat transfer and provide a more extensive coverage area and effective cooling protection. More blade-wall heat is transferred by heat conduction, which makes the area-average wall temperature for the high thermal conductivity case to decrease along the secondary flow direction. The wall temperature distribution and film cooling effectiveness are affected significantly by heat conduction.
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| 17. |
- Wang, Jinsheng, et al.
(författare)
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Conjugated heat transfer investigation with racetrack-shaped jet hole and double swirling chamber in rotating jet impingement
- 2018
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Ingår i: Numerical Heat Transfer; Part A: Applications. - : Informa UK Limited. - 1040-7782 .- 1521-0634. ; 73:11, s. 768-787
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Tidskriftsartikel (refereegranskat)abstract
- A numerical study is performed to investigate the effects of jet hole shape and channel geometry on impingement cooling for both stationary and rotating condition. Two hole shapes and two channel geometries are introduced to counteract the adverse effects of centrifugal force and Coriolis force which are induced by rotation. Both the fluid and solid part are considered for realizing the conjugate heat transfer simulation. The unsteady k-ω SST turbulence model was employed to obtain the time-averaged Nusselt number distributions, time-averaged temperature and temperature gradient fields and the turbulent flow structure. The results show that the cooling jet from the racetrack-shaped hole can effectively withstand the intensive streamwise crossflow to enhance the heat transfer. The double swirling chamber (DSC) channel significantly improves the heat transfer characteristics on the cambered surface and diminishes the adverse effects of the Coriolis force. The high Nu number region is expanded while the temperature uniformity is improved. The combination of the racetrack-shaped hole and DSC channel provides the highest heat transfer among the four cases. The averaged Nu numbers on both the leading and trailing sides for all tested cases show obvious downtrend as rotation number increases, especially at high Reynolds number.
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| 18. |
- Wang, Jinsheng, et al.
(författare)
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Numerical investigation of heat transfer and fluid flow in a rotating rectangular channel with variously-shaped discrete ribs
- 2018
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Ingår i: Applied Thermal Engineering. - : Elsevier BV. - 1359-4311. ; 129, s. 1369-1381
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Tidskriftsartikel (refereegranskat)abstract
- A numerical study is performed to investigate the effects of various discrete rib configurations on the heat transfer and fluid flow characteristics of a rotating rectangular straight channel (aspect ratio of 2:1) with 45° orientation. Three parameters of the discrete rib configuration - rib streamwise distance, rib widthwise distance, and inner-half-rib angle - are examined based on a continuous inclined rib. The blockage ratio (e/Dh) is 0.1 and the pitch ratio (P/e) is 10. The Reynolds number is fixed at 10,000 in each case, while the rotation number is varied from 0 to 0.7. Details of the turbulent flow structure, turbulence kinetic energies, temperature fields, normalized Nusselt numbers, friction penalties and thermal performance factors were obtained by Computation of Fluid Dynamics (CFD) with the k-ω SST turbulence model. The results show that a small streamwise rib gap can effectively enhance the leading wall heat transfer. The heat transfer decreases gradually as the streamwise rib gap is enlarged. The inner-half-rib angle β provides the most conspicuous effects on heat transfer and friction loss, and the best heat transfer appears at β = 60° or 75° for different rotating conditions. The case with a rib streamwise gap normalized distance of 0.2 and inner-half-rib angle of 45° provides best thermal performance. A widthwise rib gap is favorable in reducing pressure drop, but its heat transfer augmentation is limited.
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| 19. |
- Xu, Chao-Qun, et al.
(författare)
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Genome sequence of Malania oleifera, a tree with great value for nervonic acid production
- 2019
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Ingår i: GigaScience. - : Oxford University Press. - 2047-217X. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Malania oleifera, a member of the Olacaceae family, is an IUCN red listed tree, endemic and restricted to the Karst region of southwest China. This tree's seed is valued for its high content of precious fatty acids (especially nervonic acid). However, studies on its genetic makeup and fatty acid biogenesis are severely hampered by a lack of molecular and genetic tools. Findings We generated 51 Gb and 135Gb of raw DNA sequences, using Pacific Biosciences (PacBio) single-molecule real-time and 10x Genomics sequencing, respectively. A final genome assembly, with a scaffold N50 size of 4.65 Mb and a total length of 1.51Gb, was obtained by primary assembly based on PacBio long reads plus scaffolding with 10x Genomics reads. Identified repeats constituted approximate to 82% of the genome, and 24,064 protein-coding genes were predicted with high support. The genome has low heterozygosity and shows no evidence for recent whole genome duplication. Metabolic pathway genes relating to the accumulation of long-chain fatty acid were identified and studied in detail. Conclusions Here, we provide the first genome assembly and gene annotation for M. oleifera. The availability of these resources will be of great importance for conservation biology and for the functional genomics of nervonic acid biosynthesis.
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| 20. |
- Yu, Shujun, et al.
(författare)
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Macroscopic, Spectroscopic, and Theoretical Investigation for the Interaction of Phenol and Naphthol on Reduced Graphene Oxide
- 2017
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 51:6, s. 3278-3286
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Tidskriftsartikel (refereegranskat)abstract
- Interaction of phenol and naphthol with reduced graphene oxide (rGO), and their competitive behavior on rGO were examined by batch experiments, spectroscopic analysis and theoretical calculations. The batch sorption showed that the removal percentage of phenol or naphthol on rGO in bisolute systems was significantly lower than those of phenol or naphthol in single-solute systems. However, the overall sorption capacity of rGO in bisolute system was higher than single-solute system, indicating that the rGO was a very suitable material for the simultaneous elimination of organic pollutants from aqueous solutions. The interaction mechanism was mainly pi-pi interactions and hydrogen bonds, which was evidenced by FTIR, Raman and theoretical calculation. FTIR and Raman showed that a blue shift of C=C and -OH stretching modes and the enhanced intensity ratios of I-D/I-G after phenols sorption. The theoretical calculation indicated that the total hydrogen bond numbers, diffusion constant and solvent accessible surface area of naphthol were higher than those of phenol, indicating higher sorption affinity of rGO for naphthol as compared to phenol. These findings were valuable for elucidating the interaction mechanisms between phenols and graphene-based materials, and provided an essential start in simultaneous removal of organics from wastewater.
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