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Sökning: WFRF:(Li Lili)

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1.
  • de las Fuentes, Lisa, et al. (författare)
  • Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
  • 2021
  • Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
  • Tidskriftsartikel (refereegranskat)abstract
    • Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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2.
  • Turcot, Valerie, et al. (författare)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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3.
  • Chen, Anqi, et al. (författare)
  • Highly Sensitive Graphene Oxide-based Fabry-Perot Low-frequency Acoustic Sensor With Low-coherence Polarized Demodulation Using Three-step Phase-Shifting Arctan Algorithms
  • 2024
  • Ingår i: Journal of Lightwave Technology. - 0733-8724 .- 1558-2213. ; In Press
  • Tidskriftsartikel (refereegranskat)abstract
    • Developing low-frequency acoustic senor with high sensitivity is crucial for diverse applications, ranging from seismic monitoring, military operations, to pipeline surveillance. Here, we have proposed a high-sensitivity graphene oxide (GO)-based Fabry-Perot low-frequency sensor, in which a 170 nm thick, large-area and uniformly GO film was prepared by a vacuum filtration method. To enhance the accuracy and stability of the sensor, a low-coherence interference system based on birefringent crystal blocks was designed utilizing a three-step phase-shifting arctangent algorithm. Our sensor exhibited a sensitivity of -93.48 dB re 1 rad/μPa at 6-60 Hz with a fluctuation of 0.6 dB. The minimum detectable pressure of the sensor was measured at 0.37 μPa/Hz1/2 @20 Hz with a signal to noise ratio of 135.41 dB. Overall, this sensor offers simplicity in preparation, high sensitivity, low detectable sound pressure, making it a significant asset for low-frequency acoustic applications.
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4.
  • Zhang, Yanying, et al. (författare)
  • Living diatoms integrate polysaccharide-Eu3+ complex for UV downconversion
  • 2022
  • Ingår i: Journal of Materials Research and Technology. - : Elsevier. - 2238-7854. ; 19, s. 2774-2780
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, living diatoms (LDT) were fed Eu3+ -complex-polysaccharide aggregates (EIPA), and the living diatoms integrated-EIPAs (LDT-E) in a completely new UV downconversion biophotonic material. The EIPAs were embedded inside siliceous cell walls of living diatoms. When dried, these diatoms (LDT-Es) are luminescent at 612 nm, due to the Eu3+ - complex. As UV-downconversion material, LDT-E absorbs UV light in the band of 250-400 nm and converts into useful visible light, thus contributing to UV-protection and potentially to photocurrent generation in photovoltaic devices. This downconversion material from living diatom retains the porous characteristics of the diatom siliceous cells, as well as the diatom organic components. Most important is the absence of a chemical process to generate this biomaterial from natural living diatoms, in order to obtain UV protection and downconversion. (C) 2022 The Author(s). Published by Elsevier B.V.
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5.
  • de Vries, Paul S., et al. (författare)
  • Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
  • 2019
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
  • Tidskriftsartikel (refereegranskat)abstract
    • A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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6.
  • Ding, Yunmei, et al. (författare)
  • Factors influencing self-management behavior during the “Blanking Period” in patients with atrial fibrillation : A cross-sectional study based on the information-motivation-behavioral skills model
  • 2023
  • Ingår i: Heart and Lung. - : Elsevier BV. - 0147-9563. ; 58, s. 62-68
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Atrial fibrillation (AF) is becoming increasingly common. Effective self-management during the “Blanking Period” is critical. The Information-Motivation-Behavioral skills (IMB) model can be used to study health behaviors in chronic disease patients, but it has not been studied in AF patients. Objective: The goal of this study was to explore the influencing factors and interaction pathways of self-management behavior in AF patients during the "Blanking Period" using the IMB model. Methods: From June to December 2021, a cross-sectional design was conducted. Patients with AF during the "Blanking Period" (N=220) were recruited. They filled out several quantitative questionnaires, including the Jessa Atrial Fibrillation Knowledge Questionnaire, the Confidence in Atrial Fibrillation Management Scale, the Perceived Social Support Scale, the All Aspects of Health Literacy Scale, and the Self-care Scale for Chronic Atrial Fibrillation Patients. Data were analyzed using correlation analysis, multiple regression analysis, and path analysis. Results: Total score of self-management behavior was (33.83 ± 10.66). AF knowledge (β = 0.252, P < 0.001), self-management confidence (β = 0.219, P < 0.001), social support (β = 0.291, P < 0.001), and health literacy (β = 0.262, P < 0.001) were all positively correlated with patients' self-management behavior, accounting for 66.50 percent of the total variance. Conclusions: During the "Blanking Period", the IMB model can be used to predict the factors that influence self-management behavior in AF patients. By using IMB model, interventions targeting patient-specific influencing factors could improve self-management behavior and quality of life in AF patients.
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7.
  • Evangelou, Evangelos, et al. (författare)
  • Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
  • 2018
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
  • 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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8.
  • Feitosa, Mary F., et al. (författare)
  • Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
  • 2018
  • Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
  • 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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9.
  • Kato, Norihiro, et al. (författare)
  • Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
  • 2015
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
  • 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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10.
  • Lee, James J, et al. (författare)
  • Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.
  • 2018
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 50:8, s. 1112-1121
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1million individuals and identify 1,271independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.
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11.
  • Li, Lili, et al. (författare)
  • Heparanase overexpression reduces carrageenan-induced mechanical and cold hypersensitivity in mice
  • 2012
  • Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 511:1, s. 4-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Heparanase controls the structure and functions of extracellular matrix (ECM) by degrading heparan sulfate proteoglycans. Heparanase is involved in inflammatory process through modulating the functions of inflammatory cytokines. The present study aimed to find out whether overexpression of heparanase in mice affects carrageenan-induced localized inflammation and inflammatory hyperalgesia. Without challenge, the heparanase overexpression did not significantly affect the mice in response to mechanical, cold and heat stimulation. Unilateral subcutaneous administration of carrageenan produced hypersensitivity to mechanical and cold in both wildtype and the heparanase overexpression (Hpa-tg) mice 24h after treatment. In comparison to wildtype animals, the Hpa-tg mice showed significantly reduced mechanical and cold hypersensitivity. This may, at least partially, due to the reduced mast cell infiltration at the site of inflammation in Hpa-tg mice. These data support a role for heparanase that reduces localized inflammation and inflammatory hyperalgesia in mice.
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12.
  • Li, Wanxin, et al. (författare)
  • Exploring the Complex Relationship between Gut Microbiota and Risk of Colorectal Neoplasia Using Bidirectional Mendelian Randomization Analysis
  • 2023
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 32:6, s. 809-817
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Human gut microbiome has complex relation-ships with the host, contributing to metabolism, immunity, and carcinogenesis.Methods: Summary-level data for gut microbiota and metabo-lites were obtained from MiBioGen, FINRISK and human meta-bolome consortia. Summary-level data for colorectal cancer were derived from a genome-wide association study meta-analysis. In forward Mendelian randomization (MR), we employed genetic instrumental variables (IV) for 24 gut microbiota taxa and six bacterial metabolites to examine their causal relationship with colorectal cancer. We also used a lenient threshold for nine apriori gut microbiota taxa as secondary analyses. In reverse MR, we explored association between genetic liability to colorectal neoplasia and abundance of microbiota studied above using 95, 19, and 7 IVs for colorectal cancer, adenoma, and polyps, respectively.Results: Forward MR did not find evidence indicating causal relationship between any of the gut microbiota taxa or six bacterial metabolites tested and colorectal cancer risk. However, reverse MR supported genetic liability to colorectal adenomas was causally related with increased abundance of two taxa: Gammaproteobacteria (b = 0.027, which represents a 0.027 increase in log-transformed relative abundance values of Gam-maproteobacteria for per one-unit increase in log OR of adenoma risk; P = 7.06x10-8), Enterobacteriaceae (b = 0.023, P = 1.29x10-5).Conclusions: We find genetic liability to colorectal neoplasia may be associated with abundance of certain microbiota taxa. It is more likely that subset of colorectal cancer genetic liability variants changes gut biology by influencing both gut microbiota and colo-rectal cancer risk.Impact: This study highlights the need of future complemen-tary studies to explore causal mechanisms linking both host genetic variation with gut microbiome and colorectal cancer susceptibility.
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13.
  • Li, Xinxuan, et al. (författare)
  • Genetically predicted high IGF-1 levels showed protective effects on COVID-19 susceptibility and hospitalization : a Mendelian randomisation study with data from 60 studies across 25 countries
  • 2022
  • Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epidemiological studies observed gender differences in COVID-19 outcomes, however, whether sex hormone plays a causal in COVID-19 risk remains unclear. This study aimed to examine associations of sex hormone, sex hormones-binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), and COVID-19 risk. Methods: Two-sample Mendelian randomization (TSMR) study was performed to explore the causal associations between testosterone, estrogen, SHBG, IGF-1, and the risk of COVID-19 (susceptibility, hospitalization, and severity) using genome-wide association study (GWAS) summary level data from the COVID-19 Host Genetics Initiative (N=1,348,701). Random-effects inverse variance weighted (IVW) MR approach was used as the primary MR method and the weighted median, MR-Egger, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test were conducted as sensitivity analyses. Results: Higher genetically predicted IGF-1 levels have nominally significant association with reduced risk of COVID-19 susceptibility and hospitalization. For one standard deviation increase in genetically predicted IGF-1 levels, the odds ratio was 0.77 (95% confidence interval [CI], 0.61-0.97, p=0.027) for COVID-19 susceptibility, 0.62 (95% CI: 0.25-0.51, p=0.018) for COVID-19 hospitalization, and 0.85 (95% CI: 0.52-1.38, p=0.513) for COVID-19 severity. There was no evidence that testosterone, estrogen, and SHBG are associated with the risk of COVID-19 susceptibility, hospitalization, and severity in either overall or sex-stratified TSMR analysis. Conclusions: Our study indicated that genetically predicted high IGF-1 levels were associated with decrease the risk of COVID-19 susceptibility and hospitalization, but these associations did not survive the Bonferroni correction of multiple testing. Further studies are needed to validate the findings and explore whether IGF-1 could be a potential intervention target to reduce COVID-19 risk.
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14.
  • Sung, Yun Ju, et al. (författare)
  • A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
  • 2019
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
  • 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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15.
  • von Euler, Mia, 1967-, et al. (författare)
  • No protective effect of the NMDA antagonist memantine in experimental spinal cord injuries
  • 1997
  • Ingår i: Journal of Neurotrauma. - New York, USA : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 14:1, s. 53-61
  • Tidskriftsartikel (refereegranskat)abstract
    • We have investigated the effect of memantine, a clinically used NMDA receptor antagonist, in two experimental animals models of spinal cord injury. The lesions were laser-induced photothrombosis to induce focal spinal cord ischemia and clip compression to mimic traumatic spinal cord injury. Pre- or posttreatment of rats with a dose of memantine (20 mg/kg ip) previously shown to be neuroprotective in cerebral ischemia, failed to affect both the neurological and morphological outcome of ischemic spinal cord injury. Likewise, memantine had no effects on neurological and morphological outcome after experimental traumatic injury. In view of the regional heterogeneity of NMDA receptors, the affinity of memantine for spinal cord NMDA receptors was also determined by studying displacement of [3H] (+)-5-methyl-10,11-dihydro-5-H-dibenzo[a,d]cyclohepten-5-10-imine (MK-801) to rat and human spinal cord homogenates. We found that memantine had an affinity for NMDA receptors in the spinal cord (Ki = 0.58 microM) that was significantly lower compared to that of the cerebral cortex (Ki = 0.23 microM) and that the affinity for NMDA receptors in human spinal cord was even lower. We conclude that in view of available data, memantine should not be chosen for clinical studies on neuroprotection in spinal cord injuries and that the lack of protective effect is most likely due to insufficient affinity of memantine for spinal cord NMDA receptors.
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16.
  • Yu, Daniel, et al. (författare)
  • Development of a logic regression-based approach for the discovery of host- and niche-informative biomarkers in Escherichia coli and their application for microbial source tracking
  • 2024
  • Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336.
  • Tidskriftsartikel (refereegranskat)abstract
    • Microbial source tracking leverages a wide range of approaches designed to trace the origins of fecal contamination in aquatic environments. Although source tracking methods are typically employed within the laboratory setting, computational techniques can be leveraged to advance microbial source tracking methodology. Herein, we present a logic regression-based supervised learning approach for the discovery of source-informative genetic markers within intergenic regions across the Escherichia coli genome that can be used for source tracking. With just single intergenic loci, logic regression was able to identify highly source-specific (i.e., exceeding 97.00%) biomarkers for a wide range of host and niche sources, with sensitivities reaching as high as 30.00%–50.00% for certain source categories, including pig, sheep, mouse, and wastewater, depending on the specific intergenic locus analyzed. Restricting the source range to reflect the most prominent zoonotic sources of E. coli transmission (i.e., bovine, chicken, human, and pig) allowed for the generation of informative biomarkers for all host categories, with specificities of at least 90.00% and sensitivities between 12.50% and 70.00%, using the sequence data from key intergenic regions, including emrKY–evgAS, ibsB–(mdtABCD-baeSR), ompC–rcsDB, and yedS–yedR, that appear to be involved in antibiotic resistance. Remarkably, we were able to use this approach to classify 48 out of 113 river water E. coli isolates collected in Northwestern Sweden as either beaver, human, or reindeer in origin with a high degree of consensus—thus highlighting the potential of logic regression modeling as a novel approach for augmenting current source tracking efforts.
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17.
  • Yuan, Shuai, et al. (författare)
  • Health effects of high serum calcium levels : Updated phenome-wide Mendelian randomisation investigation and review of Mendelian randomisation studies
  • 2022
  • Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 76
  • Forskningsöversikt (refereegranskat)abstract
    • BackgroundCalcium plays a role in a wide range of biological functions. Here we conducted a phenome-wide Mendelian randomisation (MR-PheWAS) analysis and a systematic review for MR studies to comprehensively investigate the health effects of serum calcium.MethodsOne-hundred and thirty genetic variants strongly associated with serum calcium levels were used as instrumental variables. A phenome-wide association analysis (PheWAS) was conducted to examine the associations of genetically predicted serum calcium with 1473 distinct phenotypes in the UK Biobank including 339,197 individuals. Observed associations in PheWAS were further tested for replication in two-sample MR replication analysis. A systematic review for MR studies on serum calcium was performed to synthesize the published evidence and compare with the current MR-PheWAS findings.FindingsHigher genetically predicted calcium levels were associated with decreased risk of 5 diseases in dermatologic and musculoskeletal systems and increased risk of 17 diseases in circulatory, digestive, endocrine, genitourinary and immune systems. Eight associations were replicated in two-sample MR analysis. These included decreased risk of osteoarthritis and increased risk of coronary artery disease, myocardial infarction, coronary atherosclerosis, hyperparathyroidism, disorder of parathyroid gland, gout, and calculus of kidney and ureter with increased serum calcium. Systematic review of 25 MR studies provided supporting evidence on five out of the eight disease outcomes, while the increased risk of gout, hyperparathyroidism and disorder of parathyroid gland were novel findings.InterpretationThis study found wide-ranged health effects of high serum calcium, which suggests that the benefits and adversities of strategies promoting calcium intake should be assessed
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18.
  • Berndt, Sonja I., et al. (författare)
  • Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
  • Tidskriftsartikel (refereegranskat)abstract
    • Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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19.
  • Chen, Jie, et al. (författare)
  • Antioxidants, minerals and vitamins in relation to Crohn's disease and ulcerative colitis : A Mendelian randomization study
  • 2023
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 57:4, s. 399-408
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundEvidence for antioxidants, minerals and vitamins in relation to the risk of Crohn's disease (CD) and ulcerative colitis (UC) is limited and inconsistent. This mendelian randomization (MR) study aimed to examine the causal associations of circulating levels of antioxidants, minerals and vitamins with CD and UC.MethodsSingle-nucleotide polymorphisms associated with antioxidants (beta-carotene, lycopene and uric acid), minerals (copper, calcium, iron, magnesium, phosphorus, zinc and selenium), and vitamins (folate, vitamins A, B6, B12, C, D, E and K1) were employed as instrumental variables. Genetic associations with CD and UC were extracted from the UK Biobank, the FinnGen study and the International Inflammatory Bowel Disease Genetics Consortium. The inverse variance weighted method and sensitivity analyses were performed.ResultsGenetically predicted higher lycopene (OR = 0.94, 95% CI: 0.91–0.97), vitamins D (OR = 0.65, 95% CI: 0.54–0.79) and K1 (OR = 0.93, 95% CI: 0.90–0.97) levels were inversely associated with CD risk, whereas genetically predicted higher magnesium (OR = 1.53, 95% CI: 1.23–1.90) levels were positively associated with CD risk. Higher levels of genetically predicted lycopene (OR = 0.91, 95% CI: 0.88–0.95), phosphorus (OR = 0.69, 95% CI: 0.58–0.82), selenium (OR = 0.91, 95% CI: 0.85–0.97), zinc (OR = 0.91, 95% CI: 0.89–0.94), folate (OR = 0.71, 95% CI: 0.56–0.92) and vitamin E (OR = 0.78, 95% CI: 0.69–0.88) were associated with reduced UC risk, whereas genetically predicted high levels of calcium (OR = 1.46, 95% CI: 1.22–1.76) and magnesium (OR = 1.24, 95% CI: 1.03–1.49) were associated with increased risk of UC.ConclusionsOur study provided evidence that circulating levels of antioxidants, minerals and vitamins might be causally linked to the development of IBD.
  •  
20.
  • Chen, Jun, et al. (författare)
  • Genomic data provide new insights on the demographic history and the extent of recent material transfers in Norway spruce
  • 2019
  • Ingår i: Evolutionary Applications. - : WILEY. - 1752-4571. ; 12:8, s. 1539-1551
  • Tidskriftsartikel (refereegranskat)abstract
    • Primeval forests are today exceedingly rare in Europe, and transfer of forest reproductive material for afforestation and improvement has been very common, especially over the last two centuries. This can be a serious impediment when inferring past population movements in response to past climate changes such as the last glacial maximum (LGM), some 18,000 years ago. In the present study, we genotyped 1,672 individuals from three Picea species (P. abies, P. obovata, and P. omorika) at 400K SNPs using exome capture to infer the past demographic history of Norway spruce (P. abies) and estimate the amount of recent introduction used to establish the Norway spruce breeding program in southern Sweden. Most of these trees belong to P. abies and originate from the base populations of the Swedish breeding program. Others originate from populations across the natural ranges of the three species. Of the 1,499 individuals stemming from the breeding program, a large proportion corresponds to recent introductions from mainland Europe. The split of P. omorika occurred 23 million years ago (mya), while the divergence between P. obovata and P. abies began 17.6 mya. Demographic inferences retrieved the same main clusters within P. abies than previous studies, that is, a vast northern domain ranging from Norway to central Russia, where the species is progressively replaced by Siberian spruce (P. obovata) and two smaller domains, an Alpine domain and a Carpathian one, but also revealed further subdivision and gene flow among clusters. The three main domains divergence was ancient (15 mya), and all three went through a bottleneck corresponding to the LGM. Approximately 17% of P. abies Nordic domain migrated from P. obovata ~103K years ago, when both species had much larger effective population sizes. Our analysis of genomewide polymorphism data thus revealed the complex demographic history of Picea genus in Western Europe and highlighted the importance of material transfer in Swedish breeding program.
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21.
  • Chen, Ye, et al. (författare)
  • A global learning with local preservation method for microarray data imputation
  • 2016
  • Ingår i: Computers in Biology and Medicine. - : Elsevier. - 0010-4825 .- 1879-0534. ; 77, s. 76-89
  • Tidskriftsartikel (refereegranskat)abstract
    • Microarray data suffer from missing values for various reasons, including insufficient resolution, image noise, and experimental errors. Because missing values can hinder downstream analysis steps that require complete data as input, it is crucial to be able to estimate the missing values. In this study, we propose a Global Learning with Local Preservation method (GL2P) for imputation of missing values in microarray data. GL2P consists of two components: a local similarity measurement module and a global weighted imputation module. The former uses a local structure preservation scheme to exploit as much information as possible from the observable data, and the latter is responsible for estimating the missing values of a target gene by considering all of its neighbors rather than a subset of them. Furthermore, GL2P imputes the missing values in ascending order according to the rate of missing data for each target gene to fully utilize previously estimated values. To validate the proposed method, we conducted extensive experiments on six benchmarked microarray datasets. We compared GL2P with eight state-of-the-art imputation methods in terms of four performance metrics. The experimental results indicate that GL2P outperforms its competitors in terms of imputation accuracy and better preserves the structure of differentially expressed genes. In addition, GL2P is less sensitive to the number of neighbors than other local learning-based imputation. methods.
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22.
  • Chen, Zhi-Qiang, et al. (författare)
  • Leveraging breeding programs and genomic data in Norway spruce (Picea abies L. Karst) for GWAS analysis
  • 2021
  • Ingår i: Genome Biology. - : BioMed Central (BMC). - 1465-6906 .- 1474-760X. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Genome-wide association studies (GWAS) identify loci underlying the variation of complex traits. One of the main limitations of GWAS is the availability of reliable phenotypic data, particularly for long-lived tree species. Although an extensive amount of phenotypic data already exists in breeding programs, accounting for its high heterogeneity is a great challenge. We combine spatial and factor-analytics analyses to standardize the heterogeneous data from 120 field experiments of 483,424 progenies of Norway spruce to implement the largest reported GWAS for trees using 134 605 SNPs from exome sequencing of 5056 parental trees.Results: We identify 55 novel quantitative trait loci (QTLs) that are associated with phenotypic variation. The largest number of QTLs is associated with the budburst stage, followed by diameter at breast height, wood quality, and frost damage. Two QTLs with the largest effect have a pleiotropic effect for budburst stage, frost damage, and diameter and are associated with MAP3K genes. Genotype data called from exome capture, recently developed SNP array and gene expression data indirectly support this discovery.Conclusion: Several important QTLs associated with growth and frost damage have been verified in several southern and northern progeny plantations, indicating that these loci can be used in QTL-assisted genomic selection. Our study also demonstrates that existing heterogeneous phenotypic data from breeding programs, collected over several decades, is an important source for GWAS and that such integration into GWAS should be a major area of inquiry in the future.
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23.
  • Cheng, Ye, et al. (författare)
  • Genetic variants in the HLA region contribute to the risk of cerebral palsy
  • 2024
  • Ingår i: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE. - 0925-4439 .- 1879-260X. ; 1870:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral palsy (CP) is the most common physical disability in childhood, and genetic factors play an important role in its pathogenesis. However, the genetic contributions remain incompletely elucidated. Here, we conducted a two-stage association study between 1090 CP cases and 1100 healthy controls after whole exome sequencing. The human leukocyte antigen (HLA) allelic predispositions were further analyzed in overall CP and subgroups using multivariate logistic regression. We found a strong signal in the HLA region on chromosome 6, where rs3131787 harbored the most significant association with CP (P = 2.05 x 10-14, OR = 2.22). In comparison to controls, the carrier frequencies of HLA-B*13:02 were significantly higher in children with CP (9.82 % in control vs 19.27 % in CP, P = 1.03 x 10-4, OR = 2.17). Furthermore, the effect of HLA-B*13:02 on increasing the risk of CP mainly existed in cryptogenic CP without exposure to premature birth, low birth weight, birth asphyxia, or periventricular leukomalacia. This study indicated a strong association of HLA variants with CP, which implied that immune dysregulation resulting from immunogenetic variants might underlie the pathogenesis of CP. Our findings provide genetic evidence that an immunomodulator may serve as a promising therapeutic intervention for patients with CP by reinstating the neuroinflammation hemostasis.
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24.
  • Gu, Jian, et al. (författare)
  • TGF-beta-Induced CD4(+) Foxp3(+) T Cells Attenuate Acute Graft-versus-Host Disease by Suppressing Expansion and Killing of Effector CD8(+) Cells
  • 2014
  • Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 193:7, s. 3388-3397
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of TGF-beta-induced CD4(+) Foxp3(+) T cells (induced regulatory T cells [iTregs]) is an important prevention and treatment strategy in autoimmune diseases and other disorders. However, the potential use of iTregs as a treatment modality for acute graft-versus-host disease (aGVHD) has not been realized because they may be unstable and less suppressive in this disease. We restudied the ability of iTregs to prevent and treat aGVHD in two mouse models. Our results showed that, as long as an appropriate iTreg-generation protocol is used, these iTregs consistently displayed a potent ability to control aGVHD development and reduce mortality in the aGVHD animal models. iTreg infusion markedly suppressed the engraftment of donor CD8(+) cells and CD4(+) cells, the expression of granzyme A and B, the cytotoxic effect of donor CD8(+) cells, and the production of T cell cytokines in aGVHD. Therefore, we conclude that as long as the correct methods for generating iTregs are used, they can prevent and even treat aGVHD.
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25.
  • Ji, Zhong-Hai, et al. (författare)
  • High-throughput screening and machine learning for the efficient growth of high-quality single-wall carbon nanotubes
  • 2021
  • Ingår i: Nano Reseach. - : Tsinghua University Press. - 1998-0124 .- 1998-0000. ; 14, s. 4610-4615
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been a great challenge to optimize the growth conditions toward structure-controlled growth of single-wall carbon nanotubes (SWCNTs). Here, a high-throughput method combined with machine learning is reported that efficiently screens the growth conditions for the synthesis of high-quality SWCNTs. Patterned cobalt (Co) nanoparticles were deposited on a numerically marked silicon wafer as catalysts, and parameters of temperature, reduction time and carbon precursor were optimized. The crystallinity of the SWCNTs was characterized by Raman spectroscopy where the featured G/D peak intensity (IG/ID) was extracted automatically and mapped to the growth parameters to build a database. 1,280 data were collected to train machine learning models. Random forest regression (RFR) showed high precision in predicting the growth conditions for high-quality SWCNTs, as validated by further chemical vapor deposition (CVD) growth. This method shows great potential in structure-controlled growth of SWCNTs. [Figure not available: see fulltext.].
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26.
  • Jiang, Fangyuan, et al. (författare)
  • Association between antibiotic use during early life and early-onset colorectal cancer risk overall and according to polygenic risk and FUT2 genotypes
  • 2023
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 153:9, s. 1602-1611
  • Tidskriftsartikel (refereegranskat)abstract
    • Early-onset colorectal cancer (EOCRC) has been increasing worldwide. Potential risk factors may have occurred in childhood or adolescence. We investigated the associations between early-life factors and EOCRC risk, with a particular focus on long-term or recurrent antibiotic use (LRAU) and its interaction with genetic factors. Data on the UK Biobank participants recruited between 2006 and 2010 and followed up to February 2022 were used. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) of the associations between LRAU during early life and EOCRC risk overall and by polygenic risk score (constructed by 127 CRC-related genetic variants) and Fucosyltransferase 2 (FUT2), a gut microbiota regulatory gene. We also assessed the associations for early-onset colorectal adenomas, as precursor lesion of CRC, to examine the effect of LRAU during early-life and genetic factors on colorectal carcinogenesis. A total of 113 256 participants were included in the analysis, with 165 EOCRC cases and 719 EOCRA cases. LRAU was nominally associated with increased risk of early-onset CRC (OR = 1.48, 95% CI = 1.01-2.17, P = .046) and adenomas (OR = 1.40, 95% CI = 1.17-1.68, P < .001). When stratified by genetic polymorphisms of FUT2, LRAU appeared to confer a comparatively greater risk for early-onset adenomas among participants with rs281377 TT genotype (OR = 1.10, 95% CI = 0.79-1.52, P = .587, for CC genotype; OR = 1.75, 95% CI = 1.16-2.64, P = .008, for TT genotype; Pinteraction  = .089). Our study suggested that LRAU during early life is associated with increased risk of early-onset CRC and adenomas, and the association for adenomas is predominant among individuals with rs281377 TT/CT genotype. Further studies investigating how LRAU contributes together with genetic factors to modify EOCRC risk, particularly concerning the microbiome-related pathway underlying colorectal carcinogenesis, are warranted.
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27.
  • Kong, Jing, et al. (författare)
  • A Local Atomic Mechanism for Monoclinic-Tetragonal Phase Boundary Creation in Li-Doped Na0.5K0.5NbO3Ferroelectric Solid Solution
  • 2022
  • Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 61:10, s. 4335-4349
  • Tidskriftsartikel (refereegranskat)abstract
    • ABO3 perovskites display a wide range of phase transitions, which are driven by A/B-site centered polyhedral distortions and/or BO6 octahedral tilting. Since heterogeneous substitutions at the A/B-site can locally alter both polyhedral distortions and/or tilting, they are often used to create phase boundary regions in solid solutions of ABO3, where the functional properties are highly enhanced. However, the relationships between doping-induced atomistic structural changes and the creation of phase boundaries are not always clear. One prominent example of this is the Li-doped K0.5Na0.5NbO3 (KNNL), which is considered a promising alternative to traditional Pb-based ferroelectrics. Although the electromechanical properties of KNNL are enhanced for compositions near the morphotropic phase boundary (MPB), the atomistic mechanism for phase transitions is not well understood. Here, we combined neutron total scattering experiments and density functional theory to investigate the long-range average and short-range (∼10 Å) structural changes in KNNL. We show that the average monoclinic-to-tetragonal (M-T) transition across the MPB in KNNL can be described as an order-disorder-type change, which is driven by competition between a longer-range polarization field of monoclinic structural units and local distortions of the disordered AO12 polyhedra. The current study demonstrates a way to clarify dopant-induced local distortions near phase boundaries in complex solid solution systems, which will be important for the rational design of new environmentally sustainable ferroelectrics.
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28.
  • Li, Lili, et al. (författare)
  • Clinal variation in growth cessation and FTL2 expression in Siberian spruce
  • 2019
  • Ingår i: Tree Genetics & Genomes. - : Springer Science and Business Media LLC. - 1614-2942 .- 1614-2950. ; 15:82
  • Tidskriftsartikel (refereegranskat)abstract
    • Forest trees exhibit strong patterns of local adaptation in phenological traits along latitudinal gradients. Previous studies in spruce have shown that variation at genes from the photoperiodic pathway and the circadian clock are associated to these clines but it has been difficult to find solid evidence of selection for some of these genes. Here, we used growth cessation, gene expression, and single nucleotide polymorphism (SNP) data at two major candidate loci, FLOWERING LOCUS T/TERMINAL FLOWER1-Like2 (FTL2) and GIGANTEA (GI), as well as at background loci from a latitudinal gradient in Siberian spruce (Picea obovata) populations along the Ob River to test for clinal variation in growth cessation and at the two candidate genes. As in previous studies, there was a strong latitudinal cline in growth cessation that was accompanied by a significant cline in the expression of FTL2. Expression of FTL2 was significantly associated with allele frequencies at some of the GI’s SNPs. However, the cline in allele frequency at candidate genes was not as steep as in a Norway spruce cline and in a parallel Siberian spruce cline studied previously and nonsignificant when a correction for population structure was applied. A McDonald-Kreitman test did not detect decisive evidence of selection on GI (p value = 0.07) and could not be applied to FTL2 because of limited polymorphism. Nonetheless, polymorphisms contributed more to the increased neutrality index of PoGI than to that of control loci. Finally, comparing the results of two previously published studies to our new dataset led to the identification of strong candidate SNPs for local adaptation in FTL2 promoter and GI.
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29.
  • Li, Lili (författare)
  • Past demography and local adaptation in forest trees : Insights from natural populations and breeding programs of Norway spruce
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Spatial changes in natural selection patterns can give rise to local adaptation and genetic differentiation between populations. Local adaptation for phenological traits is pronounced in many forest tree species. The Swedish breeding program was established from ‘plus’ trees selected across the country and can therefore be a very good source of information on local adaptation. In the present thesis, we estimated the genetic basis of local adaptation in two Eurasian spruce species Norway spruce (P. abies) and Siberian species (P. obovata) using large-scale whole-exome data and Sanger sequences from samples taken from the Swedish breeding program and from natural populations.To detect signals of local adaptation in Norway spruce (P. abies), we started by studying population genetic clustering and inferring the demographic history of the species. In addition to the already known three main domains in Norway spruce, we also found four genetic clusters created by admixture events between the aforementioned three main clusters. Demographic inferences indicated two recolonizations directions in Scandinavia: east to west (from central Russia and Siberia) and south to north (from Alpine and Carpathian), but also revealed repeated hybridization between P. abies and P. obovata and gene flow among clusters. We next estimated the genetic basis of local adaptation of three phenotypic traits (height, diameter and bud-burst) by multivariate analyses and genome-wide association studies. The results showed that geographical origin is a strong predictor of growth and phenology and trees of southern origins outcompeted local provenances. We further revealed that growth traits were highly polygenic and bud-burst somewhat less.Population genetic structure largely affects the detection of local adaptation. Therefore we further visualized the fine-scale map of population genetic structure through dense sampling of trees from the Swedish breeding program. Trees of Swedish origins were assigned into two main clusters with an admixture zone in central Sweden and the genetic contribution from P. obovata was detected in northern Sweden. A large number of SNPs were found to be associated with environmental variables and exhibited a stronger pattern of isolation-by-distance than random SNPs.Finally we tested for local adaptation in two well-defined candidate genes (FTL2 and GI) of phenology in P. obovata. Clinal variation in FTL2 gene expression, growth cessation, and allele frequency of FLT2 and GI were revealed in populations along Ob River, paralleling the ones in Norway spruce populations in Scandinavia and in Siberian spruce populations along the Yenisei River.
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30.
  • Li, Lili, et al. (författare)
  • Recent introductions, ancient recolonization events and local adaptation: a first fine-scale mapping of the population genetic structure of Norway spruce across Sweden
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Population genetic structure matters for a large range of issues: it is intrinsically related to speciation and local adaptation, it informs us on past demography, it conditions the response of populations to climate change or to the spread of diseases and it severely limits the power of genome wide association studies (GWAS). In the present study we genotyped all individuals from the base population of the Swedish P. abies breeding program using exome capture. In total 4769 individuals were genotyped. This very large and dense sampling along a latitudinal gradient ranging from 55°N to 67°N, together with a large number of polymorphisms (>300,000 SNPs) allowed us to analyze population genetic structure at an unprecedented scale and to test for associations between genetic polymorphisms and environmental variables We used clustering methods (PCA, Admixture) to obtain a first genetic clustering of the data. Moreover, in order to better capture the mixture of discrete and continuous processes that generated the distribution of the genetic variation of Norway spruce across Sweden two recently developed spatialized analyses (conStruct, EEMS) were also performed. The overall data comprises both trees of Swedish origin and a large number of trees recently introduced into Sweden from the rest of the range and is highly structured with a total of six clusters representing the main postglacial refugia and admixed populations originating from the refugia. Focusing on the trees of Swedish origin, the data shows that those can be divided into two main clusters with a contact zone in central Sweden and a third small cluster in northern Sweden. The contact zone is also observed in other species and likely reflects the meeting point of the two main waves of recolonization of Scandinavia after the Last Glacial Maximum. As to the northernmost cluster it was characterized by a high contribution from P. obovata. A large number of SNPs were found to be associated to environmental variables and exhibited a stronger pattern of isolation-by-distance than random SNP. Considering that P. abies has been in Sweden for less than 50 generations, this suggests a strong selection pressure during the expansion of the species through Scandinavia. 
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31.
  • Li, Lili (författare)
  • Sex differences in acute and chronic experimental pain models
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Sex differences in response to noxious stimuli and in the development of chronic pain have been increasingly recognized and studied in humans and laboratory animals. In the clinic, extensive evidence indicates that there are a large number of chronic pain conditions that have higher prevalence in women than in men and some of these conditions, such as migraine and temporomandibular pain disorder, are also affected by the menstrual cycle. The mechanisms for sex differences in pain, particular in chronic pain, are largely unknown. The work presented in this thesis aims to explore mechanisms of sex differences using experimental pain models in rodents. In the first part of the thesis, we explored the role of estrogen receptors and the adenosine A2A receptor in sex differences in pain using genetically modified mice. We observed that in wild-type controls for estrogen receptor α or β knock-outs, females were significantly more sensitive than males to mechanical stimulation under normal condition and after carrageenan-induced inflammation. Such sex differences were eliminated in mice lacking either estrogen receptor α or β. Mechanical hypersensitivity resulting from partial sciatic nerve injury did not however differ between the sexes or between the wild-types and both estrogen receptor knock-outs. These results suggest that estrogen receptors α or β play a role in sex difference in basal mechanical pain threshold and inflammatory hypersensitivity. There was no sex difference in baseline mechanosensitivity in mice lacking the adenosine A2A receptor and wild-type controls. Carrageenan-induced mechanical hypersensitivity was significantly reduced in the A2A receptor knock-outs compared to wild-types. ZM-241,385, a selective A2A receptor antagonist, reduced inflammatory hypersensitivity in wild-type females, but not in males. The selective A2A receptor agonist CGS 21680 produced significantly more hypersensitivity in wild-type female mice than in males. These results suggest that activation of peripheral adenosine A2A receptors contributes to inflammatory hypersensitivity and that this effect is more prominent in females than in males. The second part of the thesis deals with the development of neuropathic pain-like behaviors (allodynia) in rats after spinal cord or infraorbital nerve injury. We observed a significant sex difference (females > males) in the development of mechanical allodynia after spinal cord injury in rats independent of the extent of injury. Increased mechanical hypersensitivity in females was not related to estrous stage at the time of injury. Similarly, after infraorbital nerve injury, female rats developed more persistent local and spread mechanical allodynia which was also not influenced by the estrous stages at the time or after injury. These studies provide further evidence for the presence of sex difference in baseline mechanical pain threshold, inflammatory hypersensitivity and experimental neuropathic pain in rodents. Furthermore, our results showed that estrogen receptors and adenosine A2A receptor may be involved in sex difference in pain sensitivity under normal condition or after inflammation. Finally, although female rats developed more persistent allodynia-like behaviors after spinal cord or infraorbital nerve injury, there appears to be no impact of the estrous cycle on pain development.
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32.
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33.
  • Li, Lili, et al. (författare)
  • UV-protection and fluorescence properties of the exoskeleton obtained from a living diatom modified by an Eu3+-complex
  • 2021
  • Ingår i: Journal of Materials Chemistry C. - : ROYAL SOC CHEMISTRY. - 2050-7526 .- 2050-7534. ; 9:31, s. 10005-10012
  • Tidskriftsartikel (refereegranskat)abstract
    • In this article, a natural biological porous material, from living diatoms, is used to prepare new UV-protection hybrid materials with an Eu3+-complex. By removing the organic protoplasm of living diatoms, the exoskeleton with a regular pore structure arrangement was obtained. The Eu3+-complex was chemically bonded to the exoskeleton modified by the silane coupling agent (3-aminopropyl)trimethoxy silane (APTMS). Compared with pure Eu3+-complexes, the fluorescence intensity of this hybrid material was increased by approximately 10 times. For illustrating its applications in the field of UV-protection, we mixed the USDU with polyacrylonitrile to produce flexible and transparent polymer films. The hybrid composite film (USDU@PAN) achieved partial absorption of ultraviolet light between 200 and 400 nm. At the same time, it also emits visible fluorescence and the intensity of the fluorescence is greatly increased. Therefore, the USDU@PAN film has wide application prospects in areas such as photoelectric sensors and UV-protection devices. More importantly, we transform natural organisms into materials with excellent optical properties. Therefore, it can be used in the field of UV-protection.
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34.
  • Li, Xin, et al. (författare)
  • Nanoparticle-assisted DNA nanosensor
  • 2008
  • Ingår i: AOE 2007. - SHENZHEN : AOE. - 9780978921736 ; , s. 84-86
  • Konferensbidrag (refereegranskat)abstract
    • We report a sensitive nanosensor based on a micro-fluidic chip and nanoparticles to detect low concentrations of DNA. The emission of CdSe/ZnS-QDs linked with single strand DNAs was quenched by gold nanoparticles linked with the complementary sequences after hybridization. Sensitively detected signal of DNA was obtained from a 100 mu m capillary.
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35.
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36.
  • Lin, Lili, et al. (författare)
  • First-principles investigations on the anisotropic charge transport in 4,4 '-bis((E)-2-(naphthalen-2-yl)vinyl)-1,1 '-biphenyl single crystal
  • 2014
  • Ingår i: Theoretical Chemistry accounts. - : Springer Science and Business Media LLC. - 1432-881X .- 1432-2234. ; 133:9, s. 1551-
  • Tidskriftsartikel (refereegranskat)abstract
    • We applied the master equation method to investigate the anisotropic transport property of the 4,4'-bis((E)-2-(naphthalen-2-yl)vinyl)-1,1'-biphenyl molecular crystal based on first-principles calculation. It is found that the hole mobility has the largest value along the [100] direction, while electrons have the best transport property along the [010] direction. The anisotropic transport property was found to have close relationship with the charge transfer integral which is determined by the molecular stacking network in the crystals as well as the intermolecular frontier orbital overlap. In addition, the effect of the charge carrier density and the electronic field on the charge transport was also studied, and little effect was found except that the density is larger than 0.01 and the electronic field is increased to 1.0 x 106 V/cm. The kinetic Monte Carlo simulation method has also been used to study the anisotropic charge transport property, and consistent results were obtained as with the master equation method.
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37.
  • Lou, Xiaolong, et al. (författare)
  • Distance effects on visual search and visually guided freehand interaction on large displays
  • 2022
  • Ingår i: International Journal of Industrial Ergonomics. - : Elsevier BV. - 0169-8141 .- 1872-8219. ; 90
  • Tidskriftsartikel (refereegranskat)abstract
    • Different from mouse-based and touch-based interactions at a static distance, motion-sensing interaction on a large display is typically performed at varying distances ranging from an arm's length to several metres. To investigate the effect of distance on visual search and freehand interaction performance, an empirical experiment was conducted; 30 participants were recruited to complete a series of target search and freehand selection tasks on large displays, which were 1.6 and 2.4 m wide, respectively. The results indicated that (1) the user-preferred viewing distance was positively related to the physical size of the display: a larger display size corresponded to a larger viewing distance. (2) The viewing distance had a two-sided effect on the visual search time efficiency. At a close range, increasing distance improved the search time efficiency; but at a farther range, the efficiency decreased. (3) An optimal field of view at which visual search was most efficient was found; (4) however, increasing the distance lowered freehand interaction efficiency and accuracy. Changing the distance also caused variations in the performance on divided large display areas: (5) the visual search efficiency on the upper area was higher than that on the lower area, increasing the distance reduced the difference; (6) freehand interaction efficiency and accuracy on the lower area outperformed that on the upper area, increasing the distance also reduced the difference. Implications were discussed for building more efficient and user-friendly large display-based user interfaces.
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38.
  • Ma, Tao, et al. (författare)
  • Genomic insights into salt adaptation in a desert poplar
  • 2013
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 2797-
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite the high economic and ecological importance of forests, our knowledge of the genomic evolution of trees under salt stress remains very limited. Here we report the genome sequence of the desert poplar, Populus euphratica, which exhibits high tolerance to salt stress. Its genome is very similar and collinear to that of the closely related mesophytic congener, P. trichocarpa. However, we find that several gene families likely to be involved in tolerance to salt stress contain significantly more gene copies within the P. euphratica lineage. Furthermore, genes showing evidence of positive selection are significantly enriched in functional categories related to salt stress. Some of these genes, and others within the same categories, are significantly upregulated under salt stress relative to their expression in another salt-sensitive poplar. Our results provide an important background for understanding tree adaptation to salt stress and facilitating the genetic improvement of cultivated poplars for saline soils.
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39.
  • Milesi, Pascal, et al. (författare)
  • Assessing the potential for assisted gene flow using past introduction of Norway spruce in southern Sweden : Local adaptation and genetic basis of quantitative traits in trees
  • 2019
  • Ingår i: Evolutionary Applications. - : John Wiley & Sons. - 1752-4571. ; 12:10, s. 1946-1959
  • Tidskriftsartikel (refereegranskat)abstract
    • Norway spruce (Picea abies) is a dominant conifer species of major economic importance in northern Europe. Extensive breeding programs were established to improve phenotypic traits of economic interest. In southern Sweden, seeds used to create progeny tests were collected on about 3,000 trees of outstanding phenotype (‘plus’ trees) across the region. In a companion paper, we showed that some were of local origin but many were recent introductions from the rest of the natural range. The mixed origin of the trees together with partial sequencing of the exome of >1,500 of these trees and phenotypic data retrieved from the Swedish breeding program offered a unique opportunity to dissect the genetic basis of local adaptation of three quantitative traits (height, diameter and bud-burst) and assess the potential of assisted gene flow. Through a combination of multivariate analyses and genome-wide association studies, we showed that there was a very strong effect of geographical origin on growth (height and diameter) and phenology (bud-burst) with trees from southern origins outperforming local provenances. Association studies revealed that growth traits were highly polygenic and bud-burst somewhat less. Hence, our results suggest that assisted gene flow and genomic selection approaches could help to alleviate the effect of climate change on P. abies breeding programs in Sweden.
  •  
40.
  • Parmar, Priyanka, et al. (författare)
  • Association of maternal prenatal smoking GFI1-locus and cardiometabolic phenotypes in 18,212 adults
  • 2018
  • Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 38, s. 206-216
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n= 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP). Findings: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0.012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 x 10(-7) < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 x 10(-8) < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels. Interpretation: Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. Fund: European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH.
  •  
41.
  • Song, Jiali, et al. (författare)
  • Solid additive engineering enables high-efficiency and eco-friendly all-polymer solar cells
  • 2022
  • Ingår i: Matter. - : ELSEVIER. - 2590-2393 .- 2590-2385. ; 5:11, s. 4047-4059
  • Tidskriftsartikel (refereegranskat)abstract
    • Currently, morphology optimization of all-polymer solar cells (all-PSCs) strongly depends on the use of solvent additives, which are usually highly toxic and harmful to the environment and human health. Here, we report a green and volatile solid additive, 2-methoxynaphthalene (2-MN). It was found that the incorporation of 2-MN into a PM6:PY-DT blend can effectively manipulate the aggregations of PM6 and PY-DT during film depositing and thermal annealing processes and results in highly ordered molecular packing and favorable phase-separated morphology. Consequently, a re-cord-high efficiency of 17.32% is achieved for the PM6:PY-DT de-vice. Moreover, 2-MN-processed all-PSCs were fabricated by using non-halogenated solvent. High efficiencies of 17.03% and 16.67% are obtained for all-PSCs fabricated under nitrogen atmosphere and ambient conditions, respectively. Our work shows that the utili-zation of 2-MN as a green and solid additive is a simple and feasible strategy to optimize the morphology and sheds new light on eco-friendly fabrication and application of all-PSCs.
  •  
42.
  • Sun, Yuhao, et al. (författare)
  • The Contribution of Genetic Risk and Lifestyle Factors in the Development of Adult-Onset Inflammatory Bowel Disease : A Prospective Cohort Study
  • 2023
  • Ingår i: American Journal of Gastroenterology. - : Lippincott Williams & Wilkins. - 0002-9270 .- 1572-0241. ; 118:3, s. 511-522
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: The joint associations across genetic risk, modifiable lifestyle factors, and inflammatory bowel disease (IBD) remains unclear.METHODS: Genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) was estimated by polygenic risk scores and further categorized into high, intermediate, and low genetic risk categories. Weighted healthy lifestyle scores were constructed based on 5 common lifestyle factors and categorized into favorable (4 or 5 healthy lifestyle factors), intermediate (3 healthy lifestyle factors), and unfavorable (0-2 healthy lifestyle factors) groups. Cox proportional hazards regression model was used to estimate the hazard ratios (HR) and 95% confidence interval (CI) for their associations.RESULTS: During the 12-year follow-up, 707 cases with CD and 1576 cases with UC were diagnosed in the UK Biobank cohort. Genetic risk and unhealthy lifestyle categories were monotonically associated with CD and UC risk with no multiplicative interaction between them. The HR of CD and UC were 2.24 (95% CI 1.75-2.86) and 2.15 (95% CI 1.82-2.53) for those with a high genetic risk, respectively. The HR of CD and UC for individuals with an unfavorable lifestyle were 1.94 (95% CI 1.61-2.33) and 1.98 (95% CI 1.73-2.27), respectively. The HR of individuals with a high genetic risk but a favorable lifestyle (2.33, 95% CI 1.58-3.44 for CD, and 2.05, 95% CI 1.58-2.66 for UC) were reduced nearly by half, compared with those with a high genetic risk but an unfavorable lifestyle (4.40, 95% CI 2.91-6.66 for CD and 4.44, 95% CI 3.34-5.91 for UC).DISCUSSION: Genetic and lifestyle factors were independently associated with susceptibility to incident CD and UC. Adherence to a favorable lifestyle was associated with a nearly 50% lower risk of CD and UC among participants at a high genetic risk.
  •  
43.
  • Sushko, Iurii, et al. (författare)
  • Applicability Domains for Classification Problems : Benchmarking of Distance to Models for Ames Mutagenicity Set.
  • 2010
  • Ingår i: Journal of chemical information and modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 50:12, s. 2094-2111
  • Tidskriftsartikel (refereegranskat)abstract
    • The estimation of accuracy and applicability of QSAR and QSPR models for biological and physicochemical properties represents a critical problem. The developed parameter of "distance to model" (DM) is defined as a metric of similarity between the training and test set compounds that have been subjected to QSAR/QSPR modeling. In our previous work, we demonstrated the utility and optimal performance of DM metrics that have been based on the standard deviation within an ensemble of QSAR models. The current study applies such analysis to 30 QSAR models for the Ames mutagenicity data set that were previously reported within the 2009 QSAR challenge. We demonstrate that the DMs based on an ensemble (consensus) model provide systematically better performance than other DMs. The presented approach identifies 30-60% of compounds having an accuracy of prediction similar to the interlaboratory accuracy of the Ames test, which is estimated to be 90%. Thus, the in silico predictions can be used to halve the cost of experimental measurements by providing a similar prediction accuracy. The developed model has been made publicly available at http://ochem.eu/models/1 .
  •  
44.
  • Tian, Ruifeng, et al. (författare)
  • Pressure-promoted highly-ordered Fe-doped-Ni2B for effective oxygen evolution reaction and overall water splitting
  • 2021
  • Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 9:10, s. 6469-6475
  • Tidskriftsartikel (refereegranskat)abstract
    • Accurate doping at special atomic sites can achieve effective control of active centers for the oxygen evolution reaction (OER), leading to the synthesis of active intermediates with higher conversion efficiency. Here we report the successful doping of Ni2B with Fe/Co to form highly ordered FeNiB and CoNiB electrocatalysts with a tetragonal Ni2B structure. A highly crystalline FeNiB electrode is found to have a very low polarization overpotential of 257 mV for the OER and a water splitting potential of 1.54 V at a current density of 10 mA cm(-2). XRD refinement, XPS and XAFS characterization found that doping with iron leads to the weakening of the bond strength of TM-B, which facilitates the adsorption of oxygen. During the OER process, the increasing dissolution of boron oxides promotes the effective exposure of metal active centers and boosts the catalytic performance. Theoretical calculations reveal that the substitution of Fe atoms in Ni2B make its DOS near the Fermi level higher by 2.78 times compared to that of the original Ni2B, which helps to increase the electronic conductivity and the catalytic performance.
  •  
45.
  • Wang, Aiguo, et al. (författare)
  • Microarray Missing Value Imputation : A Regularized Local Learning Method
  • 2019
  • Ingår i: IEEE/ACM Transactions on Computational Biology & Bioinformatics. - : IEEE. - 1545-5963 .- 1557-9964. ; 16:3, s. 980-993
  • Tidskriftsartikel (refereegranskat)abstract
    • Microarray experiments on gene expression inevitably generate missing values, which impedes further downstream biological analysis. Therefore, it is key to estimate the missing values accurately. Most of the existing imputation methods tend to suffer from the over-fitting problem. In this study, we propose two regularized local learning methods for microarray missing value imputation. Motivated by the grouping effect of L-2 regularization, after selecting the target gene, we train an L-2 Regularized Local Least Squares imputation model (RLLSimpute_L2) on the target gene and its neighbors to estimate the missing values of the target gene. Furthermore, RLLSimpute_L2 imputes the missing values in an ascending order based on the associated missing rate with each target gene. This contributes to fully utilizing the previously estimated values. Besides L-2, we further explore L-1 regularization and propose an L-1 Regularized Local Least Squares imputation model (RLLSimpute_L1). To evaluate their effectiveness, we conducted extensive experimental studies on six benchmark datasets covering both time series and non-time series cases. Nine state-of-the-art imputation methods are compared with RLLSimpute_L2 and RLLSimpute_L1 in terms of three performance metrics. The comparative experimental results indicate that RLLSimpute_L2 outperforms its competitors by achieving smaller imputation errors and better structure preservation of differentially expressed genes.
  •  
46.
  • Wang, Hui-Xin, et al. (författare)
  • Late Life Leisure Activities and Risk of Cognitive Decline
  • 2013
  • Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 68:2, s. 205-213
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Studies concerning the effect of different types of leisure activities on various cognitive domains are limited. This study tests the hypothesis that mental, physical, and social activities have a domain-specific protection against cognitive decline. Methods. A cohort of a geographically defined population in China was examined in 2003-2005 and followed for an average of 2.4 years. Leisure activities were assessed in 1,463 adults aged 65 years and older without cognitive or physical impairment at baseline, and their cognitive performances were tested at baseline and follow-up examinations. Results. High level of mental activity was related to less decline in global cognition (beta = -.23, p < .01), language (beta = -.11, p < .05), and executive function (beta = -.13, p < .05) in ANCOVA models adjusting for age, gender, education, history of stroke, body mass index, Apolipoprotein E genotype, and baseline cognition. High level of physical activity was related to less decline in episodic memory (beta = -.08, p < .05) and language (beta = -.15, p < .01). High level of social activity was associated with less decline in global cognition (beta = -.11, p < .05). Further, a dose-response pattern was observed: although participants who did not engage in any of the three activities experienced a significant global cognitive decline, those who engaged in any one of the activities maintained their cognition, and those who engaged in two or three activities improved their cognition. The same pattern was observed in men and in women. Conclusions. Leisure activities in old age may protect against cognitive decline for both women and men, and different types of activities seem to benefit different cognitive domains.
  •  
47.
  • Wang, Yangong, et al. (författare)
  • TEP1 is a risk gene for sporadic cerebral palsy
  • 2021
  • Ingår i: Journal of genetics and genomics. - : Elsevier BV. - 1673-8527. ; 48:12, s. 1134-1138
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
48.
  • Xiang, Yusen, et al. (författare)
  • Ginkgolic acids inhibit SARS-CoV-2 and its variants by blocking the spike protein/ACE2 interplay
  • 2023
  • Ingår i: International Journal of Biological Macromolecules. - : Elsevier. - 0141-8130 .- 1879-0003. ; 226, s. 780-792
  • Tidskriftsartikel (refereegranskat)abstract
    • Targeting the interaction between the spike protein receptor binding domain (S-RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2) is a potential therapeutic strategy for treating coronavirus disease 2019 (COVID-19). However, we still lack small-molecule drug candidates for this target due to the missing knowledge in the hot spots for the protein-protein interaction. Here, we used NanoBiT technology to identify three Ginkgolic acids from an in-house traditional Chinese medicine (TCM) library, and they interfere with the S-RBD/ACE2 interplay. Our pseudovirus assay showed that one of the compounds, Ginkgolic acid C17:1 (GA171), significantly inhibits the entry of original SARS-CoV-2 and its variants into the ACE2-overexpressed HEK293T cells. We investigated and proposed the binding sites of GA171 on S-RBD by combining molecular docking and molecular dynamics simulations. Site-directed mutagenesis and surface plasmon resonance revealed that GA171 specifically binds to the pocket near R403 and Y505, critical residues of S-RBD for S-RBD interacting with ACE2. Thus, we provide structural insights into developing new small-molecule inhibitors and vaccines against the proposed S-RBD binding site.
  •  
49.
  • Xiong, Weixi, et al. (författare)
  • Circulatory microRNA 23a and microRNA 23b and polycystic ovary syndrome (PCOS): the effects of body mass index and sex hormones in an Eastern Han Chinese population.
  • 2017
  • Ingår i: Journal of ovarian research. - : Springer Science and Business Media LLC. - 1757-2215. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • MicroRNAs (miRNAs) regulate the expression of genes involved in various cellular functions related to metabolism, inflammation, and reproduction. This study evaluated the effects of sex hormones and obesity on the expression of circulating miR-23a and miR-23b in women with polycystic ovary syndrome (PCOS) and healthy women.Serum sex hormones concentrations and body mass index (BMI) were measured in 18 women with PCOS and in 30 healthy women from the East China area and these measurements were correlated with serum miR-23a/b levels. The effect of miR-23a and miR-23b risk factors on occurrence of PCOS and predisposing factors of PCOS on these miRNA expressions were evaluated.The expressions of miR-23a/b were significantly lower in the women with PCOS than the normal women, and the expression levels of miR-23a/b were positively correlated with each other in the normal women (p=0.001) but not in the women with PCOS (p>0.05). In the women with PCOS, miR-23a was positively correlated with BMI (p=0.03). However, no correlations were found between the levels of miR-23a/b and the sex hormones in the normal and PCOS women. On the other hand, without considering the presence or absence of PCOS, increase in BMI had a positive effect on the levels of circulating miR-23b; while testosterone had negative effects on the levels of circulating miR-23a. Furthermore, the likelihood of women with PCOS decreased by 0.01-fold for every 1 fold increase of miR-23a expression.Both reduced levels and discordance between the expressions of miR-23a/b were observed in the women with PCOS and miR-23a/b were affected from testosterone and BMI, reversely. Therefore, miR-23a alteration in contrast with miR-23b is a better indicator for evaluation of PCOS than the miR-23b.
  •  
50.
  • Yang, Zhen, et al. (författare)
  • PPARG gene Pro12Ala variant contributes to the development of non-alcoholic fatty liver in middle-aged and older Chinese population
  • 2012
  • Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 348:1, s. 255-259
  • Tidskriftsartikel (refereegranskat)abstract
    • Oxidative stress has been suggested to contribute to the development of non-alcoholic fatty liver disease (NAFLD). Peroxisome proliferator-activated receptor gamma (PPAR-gamma) heterozygous mice and Pro12Ala (C/G) polymorphism in PPARG exhibited increased resistance to oxidative stress. Smoking increases the production of reactive oxygen species, which could accelerates oxidative stress under overnutrition. To explore whether the C/G polymorphism, alone or in combination with smoking, may promote the development of non-alcoholic fatty liver, a case-control study was performed in 903 Chinese subjects. Among the study population, 436 patients with B-mode ultrasound-proven NAFLD (318 with steatosis hepatis I degrees, 90 with steatosis hepatis II degrees and 28 with steatosis hepatis III degrees) and 467 controls were genotyped by using TaqMan allelic discrimination assays. After adjusting for confounders, the C/C genotype significantly associated with NAFLD (OR = 1.87, 95%CI 1.13-2.85, p = 0.009); smoking was also an independent risk factor for NAFLD (OR = 1.69, 95%CI 1.18-2.43, p = 0.025). In addition, we found possible synergistic effects, the higher risk group (smokers with the C/C genotype) showed 3.75 times higher risk of NAFLD than the low-risk group (non-smokers with C/G genotype) in a multiple logistic analysis after adjusting for the confounders (p < 0.001), but no departure from additivity was found. Our results indicated that the C/C genotype and smoking were significant independent risk factors for NAFLD. The possible synergistic effects of genotype and smoking may promote the development of NAFLD by aggravating oxidative stress, which supports the hypothesis that oxidative stress contributes to the development of NAFLD. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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