| 31. |
- Demerath, Ellen W., et al.
(författare)
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Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:15, s. 4464-4479
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is an important component of the pathophysiology of chronic diseases. Identifying epigenetic modifications associated with elevated adiposity, including DNA methylation variation, may point to genomic pathways that are dysregulated in numerous conditions. The Illumina 450K Bead Chip array was used to assay DNA methylation in leukocyte DNA obtained from 2097 African American adults in the Atherosclerosis Risk in Communities (ARIC) study. Mixed-effects regression models were used to test the association of methylation beta value with concurrent body mass index (BMI) and waist circumference (WC), and BMI change, adjusting for batch effects and potential confounders. Replication using whole-blood DNA from 2377 White adults in the Framingham Heart Study and CD4+ T cell DNA from 991 Whites in the Genetics of Lipid Lowering Drugs and Diet Network Study was followed by testing using adipose tissue DNA from 648 women in the Multiple Tissue Human Expression Resource cohort. Seventy-six BMI-related probes, 164 WC-related probes and 8 BMI change-related probes passed the threshold for significance in ARIC (P < 1 x 10(-7); Bonferroni), including probes in the recently reported HIF3A, CPT1A and ABCG1 regions. Replication using blood DNA was achieved for 37 BMI probes and 1 additional WC probe. Sixteen of these also replicated in adipose tissue, including 15 novel methylation findings near genes involved in lipid metabolism, immune response/cytokine signaling and other diverse pathways, including LGALS3BP, KDM2B, PBX1 and BBS2, among others. Adiposity traits are associated with DNA methylation at numerous CpG sites that replicate across studies despite variation in tissue type, ethnicity and analytic approaches.
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| 32. |
- Gong, Pi Xian, et al.
(författare)
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Comprehensive analysis of different types of ginsenosides in the different parts of American ginseng by targeted and nontargeted MS/MS scanning
- 2023
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Ingår i: Journal of Food Science. - : Wiley. - 0022-1147 .- 1750-3841. ; 88:12, s. 5063-5077
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: To comprehensively study the ginsenosides distribution in the various tissues of American ginseng, the qualitative and quantitative-targeted and nontargeted mass spectroscopic methods were established using the high-performance liquid chromatography coupled with Qtrap triple quadrupole mass spectrometry (HPLC-QtrapQQQ-MS). The total ginsenosides of the root, stem, and leaf of American ginseng were determined by a colorimetric method, and the contents showed the order from high to low root, stem, and leaf. Eighty-two kinds of ginsenosides were detected in the different parts of American ginseng by enhanced mass scan–information-dependent data acquisition (IDA)–enhanced product ion (EPI) scan mode, including 69 from the root, 62 from the stem, and 48 from the leaf. An HPLC–multiple reaction monitoring (MRM) method was established, and 28 representative ginsenosides were further quantified in the three parts. Nearly all ginsenosides had the highest contents in the root and the lowest content in the leaf. Three types of ginsenosides (protopanaxadiol [PPD]-, protopanaxatiol [PPT]-, and oleanolic acid [OA]-types) were analyzed by precursor ion-IDA-EPI and MRM-IDA-EPI scan modes. Root had the most abundant ginsenosides in PPD- and PPT-type ginsenosides. Meanwhile, the OA-type ginsenosides are significantly enriched in the stem and leaf of American ginseng. The results provided a supplement to the quality assessment of American ginseng. Practical Application: The distribution profile of ginsenosides in the parts of American ginseng is different. Except for the root, the stem, and leaf of American ginseng have the most abundant ginsenosides in oleanolic acid type. The results reported herein can help the manufacturers choose appropriate materials to extract the ginsenosides.
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| 33. |
- Gorski, Mathias, et al.
(författare)
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Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- 2021
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939
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Tidskriftsartikel (refereegranskat)abstract
- Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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| 34. |
- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 35. |
- Li, Dongling, et al.
(författare)
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A diatom record of mid- to late Holocene palaeoenvironmental changes in the southern Okinawa Trough
- 2015
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Ingår i: Journal of Quaternary Science. - : Wiley. - 1099-1417 .- 0267-8179. ; 30:1, s. 32-43
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Tidskriftsartikel (refereegranskat)abstract
- Palaeoceanographic changes over the last 6800 years are documented in a diatom record from core MD05-2908 from the southern Okinawa Trough. Changes in diatom components are used to reflect variations in the strength of the Kuroshio Current and the influence of coastal waters, and these changes are compared with records of the East Asian summer monsoon, which exerts an important influence on regional climate and oceanography. A decreasing trend in the contribution of coastal diatoms during the last 6800 years is related to the weakening of the East Asian summer monsoon during the Holocene in response to diminishing insolation and a southward shift in the intertropical convergence zone. Relatively high abundances of the Kuroshio Current indicator species during the intervals 2600-2200 and 4800-3600 cal a BP, and lower abundances during the intervals 3200-2800 and 2200-1300 cal a BP, imply that there is no consistent weakening of the Kuroshio Current during the interval 4500-3000 cal a BP-the Pulleniatina Minimum Event, which is a widespread feature in the East China Sea and the South China Sea. A major reduction in coastal diatoms at 3200cal a BP and a slight decrease in the Kuroshio Current indicator species during the interval 3200-2800 cal a BP indicate that a palaeoceanographic shift occurred in the southern Okinawa Trough, which coincided with a Northern Hemisphere climatic cooling, denoted the Neoglaciation in Europe. In addition, changes in the freshwater species component of the record are suggested mainly to result from variations in flood frequency in north-eastern Taiwan caused by typhoons. A dramatic increase in the frequency of flood events during the last millennium may have been caused by relatively strong El Nino-Southern Oscillation activity, compared with the more stable period between 6800 and 1000 cal a BP, which experienced a low frequency of flood events.
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| 36. |
- Li, Shenpan, et al.
(författare)
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Hepatic injury and ileitis associated with gut microbiota dysbiosis in mice upon F–53B exposure
- 2024
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 248
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Tidskriftsartikel (refereegranskat)abstract
- Chlorinated polyfluorinated ether sulfonate (F–53B), a substitute of perfluorooctane sulfonic acid (PFOS), has attracted significant attention for its link to hepatotoxicity and enterotoxicity. Nevertheless, the underlying mechanisms of F–53B-induced enterohepatic toxicity remain incompletely understood. This study aimed to explore the role of F–53B exposure on enterohepatic injury based on the gut microbiota, pathological and molecular analysis in mice. Here, we exposed C57BL/6 mice to F–53B (0, 4, 40, and 400 μg/L) for 28 days. Our findings revealed a significant accumulation of F–53B in the liver, followed by small intestines, and feces. In addition, F–53B induced pathological collagen fiber deposition and lipoid degeneration, up-regulated the expression of fatty acid β-oxidation-related genes (PPARα and PPARγ, etc), while simultaneously down-regulating pro-inflammatory genes (Nlrp3, IL-1β, and Mcp1) in the liver. Meanwhile, F–53B induced ileal mucosal barrier damage, and an up-regulation of pro-inflammatory genes and mucosal barrier-related genes (Muc1, Muc2, Claudin1, Occludin, Mct1, and ZO-1) in the ileum. Importantly, F–53B distinctly altered gut microbiota compositions by increasing the abundance of Akkermansia and decreasing the abundance of Prevotellaceae_NK3B31_group in the feces. F–53B-altered microbiota compositions were significantly associated with genes related to fatty acid β-oxidation, inflammation, and mucosal barrier. In summary, our results demonstrate that F–53B is capable of inducing hepatic injury, ileitis, and gut microbiota dysbiosis in mice, and the gut microbiota dysbiosis may play an important role in the F–53B-induced enterohepatic toxicity.
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| 37. |
- Liu, Zhiying, et al.
(författare)
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Hysteresis-free thin-film transistors achieved by novel solution-processing of nanotubes/polymer composites
- 2012
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Ingår i: Materials Research Society Spring Meeting 2012, San Francisco, April 9-13, 2012..
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Konferensbidrag (refereegranskat)abstract
- Thin-film transistors (TFTs) based on single-walled carbon nanotubes (SWCNTs) have gained enormous attention in the community of flexible/stretchable electronics. At present, such TFTs often suffer from severe problems including giant hysteresis in their transfer characteristics. With SiO2 as the gate dielectric, extensive investigations have led to generally accepted understanding of the hysteresis as being caused by charge transfer between the SWCNTs and their surroundings including both water molecules bound on the SiO2 surface (Si≡OH) and the water/oxygen molecules in the ambient atmosphere. In order to combat the hysteresis issue, significant efforts have been made by annealing the TFTs in vacuum and separating SWCNTs from SiO2 by deposition of a self-assembled monolayer (SAM) on the SiO2 or passivating the SWCNTs with an organic or inorganic dielectric film. These methods, however, require either processing in inert environment or developing elaborated processes. In the present work, we demonstrate hysteresis-free TFTs based on SWCNT/polymer composite without any complex treatment. The composite consists of SWCNTs and poly-9,9_dioctyl-fluorene-co-bithiophene (F8T2). With the aid of polymer F8T2, SWCNTs can be efficiently dissolved in commonly used solvents thereby forming a uniform composite solution. By soaking a chip with predefined TFT structures on an oxidized Si substrate in the composite solution, direct assembly of the composite on the SiO2 occurs, leading to the formation of a composite thin film in the channel region of the TFTs. Although fabricated using a very simple process, our TFTs exhibit hysteresis-free operation under ambient conditions. It is plausible to suggest that SWCNTs are embedded in the F8T2 matrix with the latter providing an effective shield for the former against the trap sites on the SiO2 and the H2O/O2 molecules in the atmosphere. In comparison to the other reported means aiming at hysteresis reduction, the present method is simple, robust, solution processable, effective, and operable under ambient conditions. In addition, we have found F8T2 to preferentially disperse semiconducting SWCNTs rendering a selective removal of the metallic species in the solution. This selectivity is of paramount importance as it results in high-performance TFTs with both high on-state current (0.1 µA/µm @ channel length = 50 µm) and large on/off current ratio (103-105). The TFTs have also shown significantly improved uniformity and dimensional scalability with a mobility value of 10-20 cm2V-1s-1, which have allowed us to investigate the TFTs using the resultant logic circuits.
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| 38. |
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| 39. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 40. |
- Proletov, Ian, et al.
(författare)
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Primary and secondary glomerulonephritides 1.
- 2014
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200
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Tidskriftsartikel (refereegranskat)
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