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- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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- Ntalla, Ioanna, et al.
(författare)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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- Albert, Damien, et al.
(författare)
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A Decade with VAMDC : Results and Ambitions
- 2020
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Ingår i: Atoms. - : MDPI. - 2218-2004. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents an overview of the current status of the Virtual Atomic and Molecular Data Centre (VAMDC) e-infrastructure, including the current status of the VAMDC-connected (or to be connected) databases, updates on the latest technological development within the infrastructure and a presentation of some application tools that make use of the VAMDC e-infrastructure. We analyse the past 10 years of VAMDC development and operation, and assess their impact both on the field of atomic and molecular (A&M) physics itself and on heterogeneous data management in international cooperation. The highly sophisticated VAMDC infrastructure and the related databases developed over this long term make them a perfect resource of sustainable data for future applications in many fields of research. However, we also discuss the current limitations that prevent VAMDC from becoming the main publishing platform and the main source of A&M data for user communities, and present possible solutions under investigation by the consortium. Several user application examples are presented, illustrating the benefits of VAMDC in current research applications, which often need the A&M data from more than one database. Finally, we present our vision for the future of VAMDC.
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- Ansari, Abdul W., et al.
(författare)
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Brief Report: Diminished Coinhibitory Molecule 2B4 Expression Is Associated With Preserved iNKT Cell Phenotype in HIV Long-Term Nonprogressors
- 2020
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Ingår i: Journal of Acquired Immune Deficiency Syndromes. - : LIPPINCOTT WILLIAMS & WILKINS. - 1525-4135 .- 1944-7884. ; 85:1, s. 73-78
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously shown an association of elevated coinhibitory molecule 2B4 expression with iNKT cells alterations in HIV disease. Herein, we show a comparative analysis of 2B4 expression on iNKT cells of HIV long-term nonprogressors (LTNPs) and progressors. Methods: Antiretroviral therapy-naive HIV-seropositive individuals (progressors, n = 16) and LTNPs (n = 10) were recruited for this study. We used multicolor flow cytometry on frozen peripheral blood mononuclear cells to determine iNKT subset frequencies, the levels of coinhibitory 2B4 expression, and intracellular interferon-gamma (IFN-gamma) production. CD1d tetramer was used to characterize iNKT cells. Results: We report significantly lower level of 2B4 expression on bulk LTNPs iNKT cells and on their CD4 subsets compared with HIV progressors. Furthermore, the iNKT cells from LTNPs produced higher amount of IFN-gamma than HIV progressors as detected by intracellular cytokine staining. Interestingly, the frequency of 2B4(+)iNKT cells of progressors but not LTNPs significantly correlates with CD4 T-cell count, HIV viral load, and IFN-gamma(+)production by iNKT cells. Conclusion: Our results suggest that in addition to suppressed HIV replication, diminished 2B4 expression and associated coinhibitory signaling, and substantial production of IFN-gamma could contribute to preserved iNKT cell phenotype in LTNPs.
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- Choi, Joong Il Jake, et al.
(författare)
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Surface Termination-Dependent Nanotribological Properties of Single-Crystal MAPbBr(3) Surfaces
- 2020
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Ingår i: The Journal of Physical Chemistry C. - : AMER CHEMICAL SOC. - 1932-7447 .- 1932-7455. ; 124:2, s. 1484-1491
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Tidskriftsartikel (refereegranskat)abstract
- Atomistic characterization of surface termination and the corresponding mechanical properties of single-crystal methylammonium lead tribromide (MAPbBr(3)) are performed using combined atomic force microscopy (AFM) measurements and density functional theory (DFT) calculations. A clean MAPbBr(3) surface is obtained by in situ cleavage in ultrahigh vacuum at room temperature, and the subsequent AFM measurements of the as-cleaved MAPbBr(3) exhibit the coexistence of two different surface terrace types with step height differences corresponding to about half the thickness of a PbI6 octahedron layer. Concurrent friction force microscopy measurements show that the two surfaces result in two distinct friction values. Based on DFT calculations, we attribute the higher-friction and lower-friction surfaces to MABr-terminated flat and PbBr2-terminated vacant surface terminations, respectively. The calculated electronic band structures of the various MABr- and PbBr2-terminated surfaces show that the midgap states are absent, revealing the defect-tolerant nature of the ideal single-crystal MAPbBr(3) surfaces.
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- Gwon, Yong-Dae, et al.
(författare)
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Antiviral Activity of Benzavir-2 against Emerging Flaviviruses
- 2020
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Most flaviviruses are arthropod-borne viruses, transmitted by either ticks or mosquitoes, and cause morbidity and mortality worldwide. They are endemic in many countries and have recently emerged in new regions, such as the Zika virus (ZIKV) in South-and Central America, the West Nile virus (WNV) in North America, and the Yellow fever virus (YFV) in Brazil and many African countries, highlighting the need for preparedness. Currently, there are no antiviral drugs available to treat flavivirus infections. We have previously discovered a broad-spectrum antiviral compound, benzavir-2, with potent antiviral activity against both DNA- and RNA-viruses. Our purpose was to investigate the inhibitory activity of benzavir-2 against flaviviruses. We used a ZIKV ZsGreen-expressing vector, two lineages of wild-type ZIKV, and other medically important flaviviruses. Benzavir-2 inhibited ZIKV derived reporter gene expression with an EC50 value of 0.8 +/- 0.1 µM. Furthermore, ZIKV plaque formation, progeny virus production, and viral RNA expression were strongly inhibited. In addition, 2.5 µM of benzavir-2 reduced infection in vitro in three to five orders of magnitude for five other flaviviruses: WNV, YFV, the tick-borne encephalitis virus, Japanese encephalitis virus, and dengue virus. In conclusion, benzavir-2 was a potent inhibitor of flavivirus infection, which supported the broad-spectrum antiviral activity of benzavir-2.
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- Laj, Paolo, et al.
(författare)
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A global analysis of climate-relevant aerosol properties retrieved from the network of Global Atmosphere Watch (GAW) near-surface observatories
- 2020
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 13:8, s. 4353-4392
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Tidskriftsartikel (refereegranskat)abstract
- Aerosol particles are essential constituents of the Earth's atmosphere, impacting the earth radiation balance directly by scattering and absorbing solar radiation, and indirectly by acting as cloud condensation nuclei. In contrast to most greenhouse gases, aerosol particles have short atmospheric residence times, resulting in a highly heterogeneous distribution in space and time. There is a clear need to document this variability at regional scale through observations involving, in particular, the in situ near-surface segment of the atmospheric observation system. This paper will provide the widest effort so far to document variability of climate-relevant in situ aerosol properties (namely wavelength dependent particle light scattering and absorption coefficients, particle number concentration and particle number size distribution) from all sites connected to the Global Atmosphere Watch network. High-quality data from almost 90 stations worldwide have been collected and controlled for quality and are reported for a reference year in 2017, providing a very extended and robust view of the variability of these variables worldwide. The range of variability observed worldwide for light scattering and absorption coefficients, single-scattering albedo, and particle number concentration are presented together with preliminary information on their long-term trends and comparison with model simulation for the different stations. The scope of the present paper is also to provide the necessary suite of information, including data provision procedures, quality control and analysis, data policy, and usage of the ground-based aerosol measurement network. It delivers to users of the World Data Centre on Aerosol, the required confidence in data products in the form of a fully characterized value chain, including uncertainty estimation and requirements for contributing to the global climate monitoring system.
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