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  • 1
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    Estimating gas saturation and recharge temperature for the abyssal ocean (2015)
    In:  EPIC326th IUGG General Assembly, Prague, Czech republic, 2015-06-22-2015-07-02
    Details
    Publication Date: 2015-07-03
    Repository Name: EPIC Alfred Wegener Institut
    Type: Conference , notRev
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  • 2
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    Epigenetic regulation of lncRNA connects ubiquitin-proteasome system with infection-inflammation in preterm births and preterm premature rupture of membranes (2015)
    BioMed Central
    Details
    Publication Date: 2015-02-16
    Description: Background: Preterm premature rupture of membranes (PPROM) is responsible for one third of all preterm births (PTBs). We have recently demonstrated that long noncoding RNAs (lncRNAs) are differentially expressed in human placentas derived from PPROM, PTB, premature rupture of the membranes (PROM), and full-term birth (FTB), and determined the major biological pathways involved in PPROM. Methods: Here, we further investigated the relationship of lncRNAs, which are differentially expressed in spontaneous PTB (sPTB) and PPROM placentas and are found to overlap a coding locus, with the differential expression of transcribed mRNAs at the same locus. Ten lncRNAs (five up-regulated and five down-regulated) and the lncRNA-associated 10 mRNAs (six up- and four down-regulated), which were identified by microarray in comparing PPROM vs. sPTB, were then validated by real-time quantitative PCR. Results: A total of 62 (38 up- and 24 down-regulated) and 1,923 (790 up- and 1,133 down-regulated) lncRNAs were identified from placentas of premature labor (sPTB?+?PPROM), as compared to those from full-term labor (FTB?+?PROM) and from premature rupture of membranes (PPROM?+?PROM), as compared to those from non-rupture of membranes (sPTB?+?FTB), respectively. We found that a correlation existed between differentially expressed lncRNAs and their associated mRNAs, which could be grouped into four categories based on the gene strand (sense or antisense) of lncRNA and its paired transcript. These findings suggest that lncRNA regulates mRNA transcription through differential mechanisms. Differential expression of the transcripts PPP2R5C, STAM, TACC2, EML4, PAM, PDE4B, STAM, PPP2R5C, PDE4B, and EGFR indicated a co-expression among these mRNAs, which are involved in the ubiquitine-proteasome system (UPS), in addition to signaling transduction and beta adrenergic signaling, suggesting that imbalanced regulation of UPS may present an additional mechanism underlying the premature rupture of membrane in PPROM. Conclusion: Differentially expressed lncRNAs that were identified from the human placentas of sPTB and PPROM may regulate their associated mRNAs through differential mechanisms and connect the ubiquitin-proteasome system with infection-inflammation pathways. Although the detailed mechanisms by which lncRNAs regulate their associated mRNAs in sPTB and PPROM are yet to be clarified, our findings open a new approach to explore the pathogenesis of sPTB and PPROM.
    Electronic ISSN: 1471-2393
    Topics: Medicine
    Published by BioMed Central
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  • 3
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    Systemic Atherosclerotic Inflammation Following Acute Myocardial Infarction: Myocardial Infarction Begets Myocardial Infarction [Imaging] (2015)
    American Heart Association (AHA)
    Details
    Publication Date: 2015-09-23
    Description: Background Preclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans. Methods and Results Overall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (≤30 days) and late (〉30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P 〈0.0001) and plasma C-reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P =0.0005) despite having similar aortic ( P =0.12) and less coronary ( P =0.006) atherosclerotic burden and similar paraspinal muscular 18F-fluorodeoxyglucose uptake ( P =0.52). Patients with ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to 〉50 000] versus 3800 [1000 to 9200] ng/L, P 〈0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P =0.03) than those with non–ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake ( r =0.43, P =0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P =0.001), but not late, recurrent MI. Conclusions The presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01749254.
    Electronic ISSN: 2047-9980
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 4
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    18F-Fluoride and 18F-Fluorodeoxyglucose Positron Emission Tomography After Transient Ischemic Attack or Minor Ischemic Stroke: Case-Control Study [Molecular Imaging] (2017)
    American Heart Association (AHA)
    Details
    Publication Date: 2017-03-22
    Description: Background— Combined positron emission tomography (PET) and computed tomography (CT) can assess both anatomy and biology of carotid atherosclerosis. We sought to assess whether 18 F-fluoride or 18 F-fluorodeoxyglucose can identify culprit and high-risk carotid plaque. Methods and Results— We performed 18 F-fluoride and 18 F-fluorodeoxyglucose PET/CT in 26 patients after recent transient ischemic attack or minor ischemic stroke: 18 patients with culprit carotid stenosis awaiting carotid endarterectomy and 8 controls without culprit carotid atheroma. We compared standardized uptake values in the clinically adjudicated culprit to the contralateral asymptomatic artery, and assessed the relationship between radiotracer uptake and plaque phenotype or predicted cardiovascular risk (ASSIGN score [Assessing Cardiovascular Risk Using SIGN Guidelines to Assign Preventive Treatment]). We also performed micro PET/CT and histological analysis of excised plaque. On histological and micro PET/CT analysis, 18 F-fluoride selectively highlighted microcalcification. Carotid 18 F-fluoride uptake was increased in clinically adjudicated culprit plaques compared with asymptomatic contralateral plaques (log 10 standardized uptake value mean 0.29±0.10 versus 0.23±0.11, P =0.001) and compared with control patients (log 10 standardized uptake value mean 0.29±0.10 versus 0.12±0.11, P =0.001). 18 F-Fluoride uptake correlated with high-risk plaque features (remodeling index [ r =0.53, P =0.003], plaque burden [ r =0.51, P =0.004]), and predicted cardiovascular risk [ r =0.65, P =0.002]). Carotid 18 F-fluorodeoxyglucose uptake appeared to be increased in 7 of 16 culprit plaques, but no overall differences in uptake were observed in culprit versus contralateral plaques or control patients. However, 18 F-fluorodeoxyglucose did correlate with predicted cardiovascular risk ( r =0.53, P =0.019), but not with plaque phenotype. Conclusions— 18 F-Fluoride PET/CT highlights culprit and phenotypically high-risk carotid plaque. This has the potential to improve risk stratification and selection of patients who may benefit from intervention.
    Keywords: Translational Studies, Imaging, Nuclear Cardiology and PET, Cerebrovascular Disease/Stroke, Atherosclerosis
    Print ISSN: 1941-9651
    Electronic ISSN: 1942-0080
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 5
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    Computed Tomography Aortic Valve Calcium Scoring in Patients With Aortic Stenosis [Valvular Heart Disease] (2018)
    American Heart Association (AHA)
    Details
    Publication Date: 2018-03-21
    Description: Background— Computed tomography aortic valve calcium scoring (CT-AVC) holds promise for the assessment of patients with aortic stenosis (AS). We sought to establish the clinical utility of CT-AVC in an international multicenter cohort of patients. Methods and Results— Patients with AS who underwent ECG-gated CT-AVC within 3 months of echocardiography were entered into an international, multicenter, observational registry. Optimal CT-AVC thresholds for diagnosing severe AS were determined in patients with concordant echocardiographic assessments, before being used to arbitrate disease severity in those with discordant measurements. In patients with long-term follow-up, we assessed whether CT-AVC thresholds predicted aortic valve replacement and death. In 918 patients from 8 centers (age, 77±10 years; 60% men; peak velocity, 3.88±0.90 m/s), 708 (77%) patients had concordant echocardiographic assessments, in whom CT-AVC provided excellent discrimination for severe AS (C statistic: women 0.92, men 0.89). Our optimal sex-specific CT-AVC thresholds (women 1377 Agatston unit and men 2062 Agatston unit) were nearly identical to those previously reported (women 1274 Agatston unit and men 2065 Agatston unit). Clinical outcomes were available in 215 patients (follow-up 1029 [126–2251] days). Sex-specific CT-AVC thresholds independently predicted aortic valve replacement and death (hazard ratio, 3.90 [95% confidence interval, 2.19–6.78]; P 〈0.001) after adjustment for age, sex, peak velocity, and aortic valve area. Among 210 (23%) patients with discordant echocardiographic assessments, there was considerable heterogeneity in CT-AVC scores, which again were an independent predictor of clinical outcomes (hazard ratio, 3.67 [95% confidence interval, 1.39–9.73]; P =0.010). Conclusions— Sex-specific CT-AVC thresholds accurately identify severe AS and provide powerful prognostic information. These findings support their integration into routine clinical practice. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT01358513, NCT02132026, NCT00338676, NCT00647088, NCT01679431.
    Keywords: Valvular Heart Disease, Computerized Tomography (CT), Echocardiography
    Print ISSN: 1941-9651
    Electronic ISSN: 1942-0080
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 6
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    Mobile genes in the human microbiome are structured from global to individual scales (2016)
    Nature Publishing Group (NPG)
    In: Nature
    Details
    Publication Date: 2016-07-21
    Description: Mobile genes in the human microbiome are structured from global to individual scales Nature 535, 7612 (2016). doi:10.1038/nature18927 Authors: I. L. Brito, S. Yilmaz, K. Huang, L. Xu, S. D. Jupiter, A. P. Jenkins, W. Naisilisili, M. Tamminen, C. S. Smillie, J. R. Wortman, B. W. Birren, R. J. Xavier, P. C. Blainey, A. K. Singh, D. Gevers & E. J. Alm Recent work has underscored the importance of the microbiome in human health, and has largely attributed differences in phenotype to differences in the species present among individuals. However, mobile genes can confer profoundly different phenotypes on different strains of the same species. Little is known about the function and distribution of mobile genes in the human microbiome, and in particular whether the gene pool is globally homogenous or constrained by human population structure. Here, we investigate this question by comparing the mobile genes found in the microbiomes of 81 metropolitan North Americans with those of 172 agrarian Fiji islanders using a combination of single-cell genomics and metagenomics. We find large differences in mobile gene content between the Fijian and North American microbiomes, with functional variation that mirrors known dietary differences such as the excess of plant-based starch degradation genes found in Fijian individuals. Notably, we also observed differences between the mobile gene pools of neighbouring Fijian villages, even though microbiome composition across villages is similar. Finally, we observe high rates of recombination leading to individual-specific mobile elements, suggesting that the abundance of some genes may reflect environmental selection rather than dispersal limitation. Together, these data support the hypothesis that human activities and behaviours provide selective pressures that shape mobile gene pools, and that acquisition of mobile genes is important for colonizing specific human populations.
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 7
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    Optimization and Reproducibility of Aortic Valve 18F-Fluoride Positron Emission Tomography in Patients With Aortic Stenosis [Molecular Imaging] (2016)
    American Heart Association (AHA)
    Details
    Publication Date: 2016-10-19
    Description: Background— 18F-Fluoride positron emission tomography (PET) and computed tomography (CT) can measure disease activity and progression in aortic stenosis. Our objectives were to optimize the methodology, analysis, and scan–rescan reproducibility of aortic valve 18F-fluoride PET-CT imaging. Methods and Results— Fifteen patients with aortic stenosis underwent repeated 18F-fluoride PET-CT. We compared nongated PET and noncontrast CT, with a modified approach that incorporated contrast CT and ECG-gated PET. We explored a range of image analysis techniques, including estimation of blood-pool activity at differing vascular sites and a most diseased segment approach. Contrast-enhanced ECG-gated PET-CT permitted localization of 18F-fluoride uptake to individual valve leaflets. Uptake was most commonly observed at sites of maximal mechanical stress: the leaflet tips and the commissures. Scan–rescan reproducibility was markedly improved using enhanced analysis techniques leading to a reduction in percentage error from ±63% to ±10% (tissue to background ratio MDS mean of 1.55, bias –0.05, limits of agreement –0·20 to +0·11). Conclusions— Optimized 18F-fluoride PET-CT allows reproducible localization of calcification activity to different regions of the aortic valve leaflet and commonly to areas of increased mechanical stress. This technique holds major promise in improving our understanding of the pathophysiology of aortic stenosis and as a biomarker end point in clinical trials of novel therapies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02132026.
    Print ISSN: 1941-9651
    Electronic ISSN: 1942-0080
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 8
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    Corrigendum: Mobile genes in the human microbiome are structured from global to individual scales (2017)
    Nature Publishing Group (NPG)
    In: Nature
    Details
    Publication Date: 2017-04-06
    Description: Corrigendum: Mobile genes in the human microbiome are structured from global to individual scales Nature 544, 7648 (2017). doi:10.1038/nature20774 Author: I. L. Brito, S. Yilmaz, K. Huang, L. Xu, S. D. Jupiter, A. P. Jenkins, W. Naisilisili, M. Tamminen, C. S. Smillie, J. R. Wortman, B. W. Birren, R. J. Xavier, P. C. Blainey, A. K. Singh, D. Gevers & E. J. Alm Nature535, 435–439 (2016); doi:10.1038/nature18927In this Letter, there were many errors in the reference citations. The original ref. 6 (Parks et al., 2015) should have been cited as ref. 32 in the Methods. There were also
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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