| 1. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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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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| 2. |
- Liu, Xiaohu, et al.
(författare)
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Biofunctionalized Gold Nanoparticles for Colorimetric Sensing of Botulinum Neurotoxin A Light Chain
- 2014
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Ingår i: Analytical Chemistry. - : American Chemical Society. - 0003-2700 .- 1520-6882. ; 86:5, s. 2345-2352
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Tidskriftsartikel (refereegranskat)abstract
- Botulinum neurotoxin is considered as one of the most toxic food-borne substances and is a potential bioweapon accessible to terrorists. The development of an accurate, convenient, and rapid assay for botulinum neurotoxins is therefore highly desirable for addressing biosafety concerns. Herein, novel biotinylated peptide substrates designed to mimic synaptosomal-associated protein 25 (SNAP-25) are utilized in gold nanoparticle-based assays for colorimetric detection of botulinum neurotoxin serotype A light chain (BoLcA). In these proteolytic assays, biotinylated peptides serve as triggers for the aggregation of gold nanoparticles, while the cleavage of these peptides by BoLcA prevents nanoparticle aggregation. Two different assay strategies are described, demonstrating limits of detection ranging from 5 to 0.1 nM of BoLcA with an overall assay time of 4 h. These hybrid enzyme-responsive nanomaterials provide rapid and sensitive detection for one of the most toxic substances known to man.
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| 3. |
- Ma, Fei, et al.
(författare)
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Association of Leukocyte Telomere Length with Mild Cognitive Impairment and Alzheimer's Disease : Role of Folate and Homocysteine
- 2019
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 48:1-2, s. 56-67
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Tidskriftsartikel (refereegranskat)abstract
- Background: Leukocyte telomere length (LTL) is associated with the aging process and age-related degenerative diseases. The relation of peripheral blood LTL to mild cognitive impairment (MCI) and Alzheimer's disease (AD) and the role of folate and homocysteine (Hcy) in this relation remain unclear.Objectives: We aimed to investigate the association between LTL and the risks of MCI/AD, and to explore whether folate and Hcy may play a role in this association.Methods: This case-control study included 129 MCI subjects, 131 AD patients and 134 healthy controls. LTL was assessed using real-time polymerase chain reaction assay. Serum folate levels were tested by chemiluminescence enzyme immunoassay, and serum Hcy levels were measured using the enzymatic cycling method. Data were analyzed using multivariate logistic regression and multivariable linear regression with adjustment for potential confounders.Results: The mean LTL was 1.56 +/- 0.25 in controls, 1.44 +/- 0.23 in MCI, and 1.28 +/- 0.28 in AD patients (p< 0.01). In multivariate logistic regression, subjects in the longest LTL tertile had lower OR for MCI (OR 0.246; 95% CI 0.101-0.597) and AD (OR 0.123; 95% CI 0.044-0.345) in comparison to subjects in the shortest tertile. Shorter LTL was dose-dependently related to the ORs of MCI and AD. Further, serum folate concentration was positively associated with LTL (p < 0.01), while serum Hcy level was negatively associated with LTL (p < 0.05). In stratified analyses, LTL-MCI/AD association varied by serum folate and Hcy level. Conclusions: Shorter LTL is associated with the risks of MCI/AD. Folate and Hcy might play an important role in this association.
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| 4. |
- Agarwal, Natasha, et al.
(författare)
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Guaranteed Success? : The Effects of Export Credit Guarantees on Firm Performance
- 2019
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Konferensbidrag (refereegranskat)abstract
- Many countries offer government-backed export credit guarantees to domestic firms. We investigate the effects of such guarantees on firm exports, jobs and value added. Using uniquely detailed and exhaustive transaction-level panel data on guarantees and granular information on trade, exporters and foreign buyers, we perform difference-indifferences matching estimations. We find that guarantees improve firm performance. However, the effects are strikingly heterogeneous across firm size and response variables. Using guarantees increases the firm-destination probability of exporting and the value of exports by 18 and 172 percent, respectively, but does not generally increase jobs or value added. Smaller firms benefit the most in terms of exports. Overall, the evidence suggests a causal link from guarantees to firm export performance.
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| 5. |
- Agarwal, Natasha, et al.
(författare)
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Institutions for Non-Simultaneous Exchange : Microeconomic Evidence from Export Insurance
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Information frictions make non-simultaneous exchange risky, particularly across borders. Therefore, many countries insure cross-border exchange. We investigate the effects on firm trade, jobs, value added and productivity, using uniquely detailed, comprehensive and longitudinal transaction-level Swedish data on insurance and granular data on exporters and foreign buyers. For identification, we employ matching and differencein-difference and fuzzy regression discontinuity estimators and exploit a quasi-natural experiment. We find strikingly heterogeneous effects across firm size and response variables. The strongest positive effects are for small traders and new users. Overall, the evidence suggests a causal link from export insurance to firm performance.
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| 6. |
- Agarwal, N., et al.
(författare)
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Mitigating information frictions in trade : Evidence from export credit guarantees
- 2023
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Ingår i: Journal of International Economics. - : Elsevier. - 0022-1996 .- 1873-0353. ; 145
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Tidskriftsartikel (refereegranskat)abstract
- Information frictions make foreign trade risky. In particular, the risk of buyer default deters firms from selling abroad. To address this issue, many countries offer export credit guarantees to provide insurance to exporters. In this paper, we investigate the causal effects of guarantees by exploiting a quasi-natural experiment in Sweden and rich register data on guarantees, firms and trade. Estimates from a fuzzy regression discontinuity design show large positive effects on the probability of exporting and the value of exports to the destination for which the guarantees are issued. These results are robust to an alternative approach using a difference-in-differences matching estimator. Further findings suggest that guarantees impact firms heterogeneously and play an important role in resolving buyer default risk and easing liquidity constraints. Larger impacts are observed in non-OECD countries, on smaller, liquidity constrained exporters and for firms selling products that face a relatively high cost of buyer default.
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| 7. |
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| 8. |
- Andrésen, Cecilia, et al.
(författare)
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Critical biophysical properties in the Pseudomonas aeruginosa efflux gene regulator MexR are targeted by mutations conferring multidrug resistance
- 2010
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Ingår i: Protein Science. - : Cold Spring Harbor Laboratory Press. - 0961-8368 .- 1469-896X. ; 19:4, s. 680-692
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Tidskriftsartikel (refereegranskat)abstract
- The self-assembling MexA-MexB-OprM efflux pump system, encoded by the mexO operon, contributes to facile resistance of Pseudomonas aeruginosa by actively extruding multiple antimicrobials. MexR negatively regulates the mexO operon, comprising two adjacent MexR binding sites, and is as such highly targeted by mutations that confer multidrug resistance (MDR). To understand how MDR mutations impair MexR function, we studied MexR-wt as well as a selected set of MDR single mutants distant from the proposed DNA-binding helix. Although DNA affinity and MexA-MexB-OprM repression were both drastically impaired in the selected MexR-MDR mutants, MexR-wt bound its two binding sites in the mexO with high affinity as a dimer. In the MexR-MDR mutants, secondary structure content and oligomerization properties were very similar to MexR-wt despite their lack of DNA binding. Despite this, the MexR-MDR mutants showed highly varying stabilities compared with MexR-wt, suggesting disturbed critical interdomain contacts, because mutations in the DNA-binding domains affected the stability of the dimer region and vice versa. Furthermore, significant ANS binding to MexR-wt in both free and DNA-bound states, together with increased ANS binding in all studied mutants, suggest that a hydrophobic cavity in the dimer region already shown to be involved in regulatory binding is enlarged by MDR mutations. Taken together, we propose that the biophysical MexR properties that are targeted by MDR mutations stability, domain interactions, and internal hydrophobic surfaces are also critical for the regulation of MexR DNA binding.
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| 9. |
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| 10. |
- Chen, Peng, et al.
(författare)
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Nanoplasmonic Sensing from the Human Vision Perspective
- 2018
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Ingår i: Analytical Chemistry. - : AMER CHEMICAL SOC. - 0003-2700 .- 1520-6882. ; 90:7, s. 4916-4924
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Tidskriftsartikel (refereegranskat)abstract
- Localized surface plasmon resonance (LSPR) constitutes a versatile technique for biodetection, exploiting the sensitivity of plasmonic nanostructures to small changes in refractive index. The optical shift in the LSPR band caused by molecular interactions in the vicinity of the nanostructures are typically amp;lt;5 nm and can readily be detected by a spectrophotometer. Widespread use of LSPR-based sensors require cost-effective devices and would benefit from sensing schemes that enables use of very simple spectrophotometers or even naked-eye detection. This paper describes a new strategy facilitating visualization of minute optical responses in nanoplasmonic bioassays by taking into account the physiology of human color vision. We demonstrate, using a set of nine different plasmonic nanoparticles, that the cyan to green transition zone at similar to 500 nm is optimal for naked-eye detection of color changes. In this wavelength range, it is possible to detect a color change corresponding to a wavelength shift of similar to 2-3 nm induced by refractive index changes in the medium or by molecular binding to the surface of the nanoparticles. This strategy also can be utilized to improve the performance of aggregation-based nanoplasmonic colorimetric assays, which enables semiquantitative naked-eye detection of matrix metalloproteinase 7 (MMP7) activity at concentrations that are at least 5 times lower than previously reported assays using spherical gold nanoparticles. We foresee significant potential of this strategy in medical diagnostic and environmental monitoring, especially in situations where basic laboratory infrastructure is sparse or even nonexistent. Finally, we demonstrate that the developed concept can be used in combination with cell phone technology and red-green-blue (RGB) analysis for sensitive and quantitative detection of MMP7.
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| 11. |
- Wang, Yusong, et al.
(författare)
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Specific functionalization of CTAB stabilized anisotropic gold nanoparticles with polypeptides for folding-mediated self-assembly
- 2012
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Ingår i: Journal of Materials Chemistry. - : Royal Society of Chemistry. - 0959-9428 .- 1364-5501. ; 22:38, s. 20368-20373
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Tidskriftsartikel (refereegranskat)abstract
- Anisotropic nanoparticles stabilized by cetyltrimethylammonium bromide (CTAB) are notoriously difficult to homogenously functionalize using conventional gold-thiol chemistry. Using surface assisted laser desorption time of flight mass spectroscopy and scanning transmission electron microscopy-energy dispersive X-ray spectroscopy, we demonstrate that silver species adsorbed on the particle surface prevent effective surface functionalization. When covered by a thin gold film, particle functionalization was drastically improved. A thiol-containing polypeptide was immobilized on arrowhead gold nanorods (NRs) and was subsequently able to selectively heteroassociate with a complementary polypeptide resulting in a folding-mediated bridging aggregation of the NRs. Despite using arrowhead NRs with a pronounced difference in surface arrangement on the {111} facets on the arrowheads compared to the {100} facets at the particle sides, the polypeptides were efficiently and homogeneously immobilized on the particles after gold film overgrowth.
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| 12. |
- Wang, Yi, et al.
(författare)
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Time-resolved botulinum neurotoxin A activity monitored using peptide-functionalized Au nanoparticle energy transfer sensors
- 2014
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Ingår i: Chemical Science. - : Royal Society of Chemistry. - 2041-6520 .- 2041-6539. ; 5:7, s. 2651-2656
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Tidskriftsartikel (refereegranskat)abstract
- We report herein on the employment of synthetic peptide-functionalized gold nanoparticles (AuNPs) with various diameters as radiative quenchers for the time-resolved monitoring of botulinum A light chain (BoLcA) activity. The results demonstrate that larger AuNPs provide higher energy transfer efficiencies between the dye and the AuNPs, but poorer BoLcA activities for the proteolysis of peptides because of steric constraints. The initial turnover number for the BoLcA proteolysis of peptides on 18 nm AuNPs was retarded by a factor of 80 as compared with 1.4 nm AuNPs. A similar phenomenon has been observed for trypsin, however, with less hindrance on large AuNPs. Thus, the use of smaller 1.4 nm AuNPs in conjunction with robust synthetic peptides provides an attractive format for the time-resolved monitoring of protease activity and for BoLcA sensing at a highly competitive limit of detection (1 pM).
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| 13. |
- Wickham, Abeni, et al.
(författare)
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Near-Infrared Emitting and Pro-Angiogenic Electrospun Conjugated Polymer Scaffold for Optical Biomaterial Tracking
- 2015
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Ingår i: Advanced Functional Materials. - : Wiley: 12 months. - 1616-301X .- 1616-3028. ; 25:27, s. 4274-4281
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Tidskriftsartikel (refereegranskat)abstract
- Noninvasive tracking of biomaterials is vital for determining the fate and degradation of an implant in vivo, and to show its role in tissue regeneration. Current biomaterials have no inherent capacity to enable tracing but require labeling with, for example, fluorescent dyes, or nanoparticles. Here a novel biocompatible fully conjugated electrospun scaffold is described, based on a semiconducting luminescent polymer that can be visualized in situ after implantation using fluorescence imaging. The polymer, poly [2,3-bis-(3-octyloxyphenyl)quinoxaline-5,8-diyl-alt -thiophene-2,5-diyl] (TQ1), is electrospun to form a fibrous mat. The fibers display fluorescence emission in the near-infrared region with lifetimes in the sub-nanosecond range, optimal for in situ imaging. The material shows no cytotoxic behaviors for embryonic chicken cardiomyocytes and mouse myoblasts, and cells migrate onto the TQ1 fibers even in the presence of a collagen substrate. Subcutaneous implantations of the material in rats show incorporation of the TQ1 fibers within the tissue, with limited inflammation and a preponderance of small capillaries around the fibers. The fluorescent properties of the TQ1 fibers are fully retained for up to 90 d following implantation and they can be clearly visualized in tissue using fluorescence and lifetime imaging, thus making it both a pro-angiogenic and traceable biomaterial.
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| 14. |
- Zhang, Hongwei, et al.
(författare)
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Influences of Flow Intensity, Cooling Rate and Nucleation Density at Ingot Surface on Deflective Growth of Dendrites for Al-based Alloy
- 2009
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Ingår i: ISIJ International. - : Iron and Steel Institute of Japan. - 0915-1559 .- 1347-5460. ; 49:7, s. 1010-1018
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Tidskriftsartikel (refereegranskat)abstract
- The dendrite tip growth kinetics in the flow field and the decentred quadrilateral growth algorithm for describing the evolution of grain growth are combined in Cellular Automaton model to predict the deflective growth of dendrites inclined toward upstream direction. The influences of flow intensity, cooling rate (or solidification rate), nucleation density at ingot surface on the deflective growth of dendrites are discussed. The increase of flow intensity dominantly forces the dendrites to grow in upstream direction; on the contrary, the increases of nucleation density at ingot surface and cooling rate suppress slightly this deflective growth. The relations predicted among deflection angle, flow intensity and solidification rate for AI-Si alloy and Al-Cu alloy show the same tendency as that in Okano et al.'s empirical expression deduced from experiments on steel. The deflection angle predicted for Al-Cu alloy fits well with previous experimental results.
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