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  • 1
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    Wall shear stress and flow patterns in the ascending aorta in patients with bicuspid aortic valves differ significantly from tricuspid aortic valves: a prospective study (2013)
    Oxford University Press
    Details
    Publication Date: 2013-07-12
    Description: Aims We compared flow and wall shear stress (WSS) patterns in the ascending aorta of individuals with either bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) using four-dimensional cardiovascular magnetic resonance (4D-CMR). BAV are known to be associated with dilation and dissection of the ascending aorta. However, the cause of vessel disease in patients with BAVs is unknown. Inborn connective tissue disease and also dilation secondary to increased WSS because of altered blood flow patterns in the ascending aorta are discussed as causes for dilation of the aorta. WSS can be estimated non-invasively by 4D-CMR. Methods and results Eighteen, otherwise, healthy individuals with functionally normal BAVs were compared prospectively with an age- and sex-matched control group of healthy individuals with TAV. Blood flow data were obtained by 4D-CMR visualization and WSS was calculated with specific software tools. Eighty-five per cent of the individuals with BAVs showed a high-grade helical flow pattern in the ascending aorta compared with 6% of the individuals with TAV. WSS in the ascending aorta was significantly altered in individuals with BAVs compared with TAV. Conclusion WSS and flow patterns in the ascending aorta in patients with BAVs without concomitant valve or vessel disease are significantly different compared with TAV. The significantly higher shear forces may have an impact on the development of aortic dilation in patients with BAVs.
    Print ISSN: 1525-2167
    Electronic ISSN: 1532-2114
    Topics: Medicine
    Published by Oxford University Press
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  • 2
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    Acute and long-term outcome after catheter ablation of supraventricular tachycardia in patients after the Mustard or Senning operation for D-transposition of the great arteries (2013)
    Oxford University Press
    In: Europace
    Details
    Publication Date: 2013-05-25
    Description: Aims Data about the acute and long-term outcome of catheter ablation in patients with D-transposition of the great arteries (d-TGA) post-Mustard/Senning operation are scarce. Methods and results This single-centre retrospective analysis includes 26 patients (mean age 28.7 ± 6.7 years, 8 females) after Mustard ( n = 15) or Senning ( n = 11) operation who underwent catheter ablation for intra-atrial re-entrant tachycardia (IART) or atrioventricular nodal re-entrant tachycardia (AVNRT) from January 2004 to May 2011. The electrophysiological studies were performed using a three-dimensional mapping system (CARTO ® ). Remote magnetic navigation (RMN) was available since 2008. Follow-up on an outpatient basis was conducted 3, 6, and 12 months after ablation and yearly thereafter. In the 26 patients, 34 procedures were performed (one procedure n = 19, two n = 6, and three n = 1). Overall, 34 tachycardia forms (IART n = 30; AVNRT n = 4) were ablated manually ( n = 25) or by RMN ( n = 9). Acute success reached in 29/34 forms (85.3%). Mean fluoroscopy time (FT) was 28.2 ± 20.7 min and mean procedure duration (PD) was 290.9 ± 107.6 min. After a mean follow-up of 34.1 ± 24.5 months, 25/26 (96.2%) patients were free from IART or AVNRT. In the nine RMN ablations (mean follow-up 14.2 ± 5.8 months) acute and long-term success was 100%. Fluoroscopy time and PD were significantly reduced using RMN compared with manual ablation (11.9 ± 6.2 vs. 34.6 ± 20.6 min, 225.7 ± 24.1 vs. 312 ± 118.2 min, P = 0.02). Conclusion Catheter ablation of IART or AVNRT in patients post-Mustard/Senning operation for d-TGA has a high acute success rate. The recurrence rate for IART is about 30%; however, after a second ablation, long-term results are excellent. Remote magnetic navigation seems to improve single-procedure acute and long-term success and significantly reduces FT and PD.
    Print ISSN: 1099-5129
    Electronic ISSN: 1532-2092
    Topics: Medicine
    Published by Oxford University Press
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  • 3
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    Dose-dependent expression of CLIP2 in post-Chernobyl papillary thyroid carcinomas (2015)
    Oxford University Press
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    Publication Date: 2015-07-10
    Description: A previous study on papillary thyroid carcinomas (PTC) in young patients who were exposed to 131 iodine from the Chernobyl fallout revealed an exclusive gain of chromosomal band 7q11.23 in exposed cases compared to an age-matched control cohort. CLIP2, a gene located within band 7q11.23 was shown to be differentially expressed between exposed and non-exposed cases at messenger RNA and protein level. Therefore, a standardized procedure for CLIP2 typing of PTCs has been developed in a follow-up study. Here we used CLIP2 typing data on 117 post-Chernobyl PTCs from two cohorts of exposed patients with individual dose estimates and 24 non-exposed controls to investigate a possible quantitative dose-response relationship of the CLIP2 marker. The ‘Genrisk-T’ cohort consisted of 45 PTCs and the ‘UkrAm’ cohort of 72 PTCs. Both cohorts differed in mean dose (0.59 Gy Genrisk-T, 1.2 Gy UkrAm) and mean age at exposure (AaE) (2 years Genrisk-T, 8 years UkrAm), whilst the median latency (16 years Genrisk-T, 18 years UkrAm) was comparable. We analyzed the association between the binary CLIP2 typing and continuous thyroid dose with logistic regression. A clear positive dose-response relationship was found for young PTC cases [age at operation (AaO) 〈 20 years, AaE 〈 5 years]. In the elder age group a higher proportion of sporadic tumors is assumed due to a negligible dose response, suggesting different molecular mechanisms in sporadic and radiation-induced cases. This is further supported by the association of elder patients (AaO 〉 20 years) with positivity for BRAF V600E mutation.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
    Published by Oxford University Press
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  • 4
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    Expression of podoplanin in human astrocytic brain tumors is controlled by the PI3K-AKT-AP-1 signaling pathway and promoter methylation (2012)
    Oxford University Press
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    Publication Date: 2012-04-16
    Description: Recently, we found strong overexpression of the mucin-type glycoprotein podoplanin (PDPN) in human astrocytic brain tumors, specifically in primary glioblastoma multiforme (GB). In the current study, we show an inverse correlation between PDPN expression and PTEN levels in primary human GB and glioma cell lines, and we report elevated PDPN protein levels in the subventricular zone of brain tissue sections of PTEN-deficient mice. In human glioma cells lacking functional PTEN, reintroduction of wild-type PTEN, inhibition of the PTEN downstream target protein kinase B/AKT, or interference with transcription factor AP-1 function resulted in efficient downregulation of PDPN expression. In addition, we observed hypoxia-dependent PDPN transcriptional control and demonstrated that PDPN expression is subject to negative transcriptional regulation by promoter methylation in human GB and in glioma cell lines. Treatment of PTEN-negative glioma cells with demethylating agents induced expression of PDPN. Together, our findings show that increased PDPN expression in human GB is caused by loss of PTEN function and activation of the PI3K-AKT-AP-1 signaling pathway, accompanied by epigenetic regulation of PDPN promoter activity. Silencing of PDPN expression leads to reduced proliferation and migration of glioma cells, suggesting a functional role of PDPN in glioma progression and malignancy. Thus, specific targeting of PDPN expression and/or function could be a promising strategy for the treatment of patients with primary GB.
    Print ISSN: 1522-8517
    Electronic ISSN: 1523-5866
    Topics: Medicine
    Published by Oxford University Press on behalf of The Society for Neuro-Oncology (SNO).
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  • 5
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    Transposable Element Dynamics among Asymbiotic and Ectomycorrhizal Amanita Fungi (2014)
    Oxford University Press
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    Publication Date: 2014-07-04
    Description: Transposable elements (TEs) are ubiquitous inhabitants of eukaryotic genomes and their proliferation and dispersal shape genome architectures and diversity. Nevertheless, TE dynamics are often explored for one species at a time and are rarely considered in ecological contexts. Recent work with plant pathogens suggests a link between symbiosis and TE abundance. The genomes of pathogenic fungi appear to house an increased abundance of TEs, and TEs are frequently associated with the genes involved in symbiosis. To investigate whether this pattern is general, and relevant to mutualistic plant-fungal symbioses, we sequenced the genomes of related asymbiotic (AS) and ectomycorrhizal (ECM) Amanita fungi. Using methods developed to interrogate both assembled and unassembled sequences, we characterized and quantified TEs across three AS and three ECM species, including the AS outgroup Volvariella volvacea . The ECM genomes are characterized by abundant numbers of TEs, an especially prominent feature of unassembled sequencing libraries. Increased TE activity in ECM species is also supported by phylogenetic analysis of the three most abundant TE superfamilies; phylogenies revealed many radiations within contemporary ECM species. However, the AS species Amanita thiersii also houses extensive amplifications of elements, highlighting the influence of additional evolutionary parameters on TE abundance. Our analyses provide further evidence for a link between symbiotic associations among plants and fungi, and increased TE activity, while highlighting the importance individual species’ natural histories may have in shaping genome architecture.
    Electronic ISSN: 1759-6653
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    Early subcellular Ca2+ remodelling and increased propensity for Ca2+ alternans in left atrial myocytes from hypertensive rats (2015)
    Oxford University Press
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    Publication Date: 2015-03-18
    Description: Aims Hypertension is a major risk factor for atrial fibrillation. We hypothesized that arterial hypertension would alter atrial myocyte calcium (Ca 2+ ) handling and that these alterations would serve to trigger atrial tachyarrhythmias. Methods and results Left atria or left atrial (LA) myocytes were isolated from spontaneously hypertensive rats (SHR) or normotensive Wistar-Kyoto (WKY) controls. Early after the onset of hypertension, at 3 months of age, there were no differences in Ca 2+ transients (CaTs) or expression and phosphorylation of Ca 2+ handling proteins between SHR and WKY. At 7 months of age, when left ventricular (LV) hypertrophy had progressed and markers of fibrosis were increased in left atrium, CaTs (at 1 Hz stimulation) were still unchanged. Subcellular alterations in Ca 2+ handling were observed, however, in SHR atrial myocytes including (i) reduced expression of the α1C subunit of and reduced Ca 2+ influx through L-type Ca 2+ channels, (ii) reduced expression of ryanodine receptors with increased phosphorylation at Ser2808, (iii) decreased activity of the Na + /Ca 2+ exchanger (at unaltered intracellular Na + concentration), and (iv) increased SR Ca 2+ load with reduced fractional release. These changes were associated with an increased propensity of SHR atrial myocytes to develop frequency-dependent, arrhythmogenic Ca 2+ alternans. Conclusions In SHR, hypertension induces early subcellular LA myocyte Ca 2+ remodelling during compensated LV hypertrophy. In basal conditions, atrial myocyte CaTs are not changed. At increased stimulation frequency, however, SHR atrial myocytes become more prone to arrhythmogenic Ca 2+ alternans, suggesting a link between hypertension, atrial Ca 2+ homeostasis, and development of atrial tachyarrhythmias.
    Print ISSN: 0008-6363
    Electronic ISSN: 1755-3245
    Topics: Medicine
    Published by Oxford University Press
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  • 7
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    Genomic copy number analysis of Chernobyl papillary thyroid carcinoma in the Ukrainian-American Cohort (2015)
    Oxford University Press
    Details
    Publication Date: 2015-10-30
    Description: One of the major consequences of the 1986 Chernobyl reactor accident was a dramatic increase in papillary thyroid carcinoma (PTC) incidence, predominantly in patients exposed to the radioiodine fallout at young age. The present study is the first on genomic copy number alterations (CNAs) of PTCs of the Ukrainian–American cohort (UkrAm) generated by array comparative genomic hybridization (aCGH). Unsupervised hierarchical clustering of CNA profiles revealed a significant enrichment of a subgroup of patients with female gender, long latency (〉17 years) and negative lymph node status. Further, we identified single CNAs that were significantly associated with latency, gender, radiation dose and BRAF V600E mutation status. Multivariate analysis revealed no interactions but additive effects of parameters gender, latency and dose on CNAs. The previously identified radiation-associated gain of the chromosomal bands 7q11.22-11.23 was present in 29% of cases. Moreover, comparison of our radiation-associated PTC data set with the TCGA data set on sporadic PTCs revealed altered copy numbers of the tumor driver genes NF2 and CHEK2. Further, we integrated the CNA data with transcriptomic data that were available on a subset of the herein analyzed cohort and did not find statistically significant associations between the two molecular layers. However, applying hierarchical clustering on a ‘BRAF-like/RAS-like’ transcriptome signature split the cases into four groups, one of which containing all BRAF-positive cases validating the signature in an independent data set.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
    Published by Oxford University Press
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  • 8
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    Engineering large Stark shifts for control of individual clock state qubits (2016)
    American Physical Society (APS)
    Details
    Publication Date: 2016-10-11
    Description: Author(s): A. C. Lee, J. Smith, P. Richerme, B. Neyenhuis, P. W. Hess, J. Zhang, and C. Monroe In quantum information science, the external control of qubits must be balanced with the extreme isolation of the qubits from the environment. Atomic qubit systems typically mitigate this balance through the use of gated laser fields that can create superpositions and entanglement between qubits. He… [Phys. Rev. A 94, 042308] Published Fri Oct 07, 2016
    Keywords: Quantum information
    Print ISSN: 1050-2947
    Electronic ISSN: 1094-1622
    Topics: Physics
    Published by American Physical Society (APS)
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  • 9
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    Differential adult migration-timing and stock-specific abundance of steelhead in mixed stock assemblages (2016)
    Oxford University Press
    Details
    Publication Date: 2016-12-10
    Description: Stock-specific migration-timing and relative abundance of exploited fish species are critical parameters to estimate for management of mixed stock fisheries. Here, we used parentage-based tagging (PBT) together with mixed stock analyses (MSA) to estimate stock-specific abundance and migration-timing in anadromous adult steelhead ( Oncorhynchus mykiss ) sampled at Bonneville Dam in the lower Columbia River. Results indicate that natural-origin steelhead was represented by 11 of 13 possible stocks found throughout the Columbia-Snake river basins, while hatchery-origin steelhead was primarily composed of five stocks from the Snake River drainage. Further, migration-timing differentiated stocks and allowed categorization of early, intermediate, and late migrating stocks. Analyses of age and length data for these stocks also showed that late-arriving fish were larger due to older age and originated primarily from the Clearwater River, South Fork Salmon River, and Dworshak Hatchery, all from the Snake River drainage. Sex ratios tended to be skewed towards females and ranged from 51.5 to 68.9% for hatchery stocks and 60.5–71.8% for natural-origin stocks. This suggests that anadromous migration is favored by females while males are more likely to residualize in freshwater. Overall, this study demonstrates how the use of PBT in MSA can reveal important stock-specific differences in migration-timing and relative abundance and provides critical information for management of mixed stock fisheries.
    Print ISSN: 1054-3139
    Electronic ISSN: 1095-9289
    Topics: Biology , Geosciences , Physics
    Published by Oxford University Press
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  • 10
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    Migrating adult steelhead utilize a thermal refuge during summer periods with high water temperatures (2016)
    Oxford University Press
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    Publication Date: 2016-12-10
    Description: Anadromous fishes often use various survival tactics while migrating through main stem rivers to successfully reach spawning grounds and reproduce. Mixed-stock assemblages of anadromous adult summer steelhead Oncorhynchus mykiss re-enter the Columbia River from late spring through fall including the period of peak summer water temperatures, and previous studies suggest that stocks alter migratory behaviour in response to warm temperatures by seeking cool water refuges. We combined parentage-based tagging with mixed stock analyses to test whether steelhead use a non-natal tributary (Deschutes River, OR, USA) as a thermal refuge and if this migratory behaviour is associated with stock-specific run-timing. Results collected over two migration years indicated that out-of-basin fish in the Deschutes River were disproportionately from specific stocks in the Snake River (Salmon and Grande Ronde) that had migrated through the main stem Columbia River when water temperatures exceeded 21 °C. Stocks migrating through the main stem river during cooler temperature periods were either less frequent (Clearwater River), or not encountered (lower Snake River) in the Deschutes River. This study facilitates an improved understanding of stock-specific migratory characteristics associated with environmental conditions in this system. Results potentially affect fisheries management, hatchery protocols, cool-water refuge maintenance, and conservation of wild Deschutes River populations.
    Print ISSN: 1054-3139
    Electronic ISSN: 1095-9289
    Topics: Biology , Geosciences , Physics
    Published by Oxford University Press
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