| 1. |
- Abazov, V. M., et al.
(författare)
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The upgraded DO detector
- 2006
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 565:2, s. 463-537
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Tidskriftsartikel (refereegranskat)abstract
- The DO experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid -argon calorimeters and central muon detector, remaining from Run 1, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to DO.
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| 2. |
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| 3. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 4. |
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| 5. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 14. |
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| 15. |
- Chalmers, J. R., et al.
(författare)
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Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME)
- 2014
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 171:6, s. 1318-1325
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Tidskriftsartikel (refereegranskat)abstract
- This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure.
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| 16. |
- Ermund, Anna, et al.
(författare)
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The normal trachea is cleaned by MUC5B mucin bundles from the submucosal glands coated with the MUC5AC mucin
- 2017
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 492:3, s. 331-337
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Tidskriftsartikel (refereegranskat)abstract
- To understand the mucociliary clearance system, mucins were visualized by light, confocal and electron microscopy, and mucus was stained by Alcian blue and tracked by video microscopy on tracheal explants of newborn piglets. We observed long linear mucus bundles that appeared at the submucosal gland openings and were transported cephalically. The mucus bundles were shown by mass spectrometry and immunostaining to have a core made of MUC5B mucin and were coated with MUC5AC mucin produced by surface goblet cells. The transport speed of the bundles was slower than the airway surface liquid flow. We suggest that the goblet cell MUC5AC mucin anchors the mucus bundles and thus controls their transport. Normal clearance of the respiratory tree of pigs and humans, both rich in submucosal glands, is performed by thick and long mucus bundles. (C) 2017 The Authors. Published by Elsevier Inc.
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| 17. |
- Hudson, Lawrence N., et al.
(författare)
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The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
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Tidskriftsartikel (refereegranskat)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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| 18. |
- Kirkpatrick, Christine L., et al.
(författare)
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The "PepSAVI-MS" Pipeline for Natural Product Bioactive Peptide Discovery
- 2017
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 89:2, s. 1194-1201
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Tidskriftsartikel (refereegranskat)abstract
- The recent increase in extensively drug-resistant bacterial pathogens and the associated increase of morbidity and mortality demonstrate the immediate need for new antibiotic backbones with novel mechanisms of action. Here, we report the development of the PepSAVI-MS pipeline for bioactive peptide discovery. This highly versatile platform employs mass spectrometry and statistics to identify bioactive peptide targets from complex biological samples. We validate the use of this platform through the successful identification of known bioactive peptides from a botanical species, Viola odorata. Using this pipeline, we have widened the known antimicrobial spectrum for V. odorata cyclotides, including antibacterial activity of cycloviolacin O2 against A. baumannii. We further demonstrate the broad applicability of the platform through the identification of novel anticancer activities for cycloviolacins by their cytotoxicity against ovarian, breast, and prostate cancer cell lines.
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| 19. |
- Trillo-Muyo, Sergio, 1983, et al.
(författare)
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Granule-stored MUC5B mucins are packed by the non-covalent formation of N-terminal head-to-head tetramers
- 2018
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Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 293:15, s. 5746-5754
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Tidskriftsartikel (refereegranskat)abstract
- Most MUC5B mucin polymers in the upper airways of humans and pigs are produced by submucosal glands. MUC5B forms N-terminal covalent dimers that are further packed into larger assemblies because of low pH and high Ca2+ in the secretory granule of the mucin-producing cell. We purified the recombinant MUC5B N-terminal covalent dimer and used single-particle electron microscopy to study its structure under intracellular conditions. We found that, at intragranular pH, the dimeric MUC5B organized into head-to-head noncovalent tetramers where the von Willebrand D1-D2 domains hooked into each other. These N-terminal tetramers further formed long linear complexes from which, we suggest, the mucin domains and their C termini project radially outwards. Using conventional and video microscopy, we observed that, upon secretion into the submucosal gland ducts, a flow of bicarbonate-rich fluid passes the mucin-secreting cells. We suggest that this unfolds and pulls out the MUC5B assemblies into long linear threads. These further assemble into thicker mucin bundles in the glandular ducts before emerging at the gland duct opening. We conclude that the combination of intracellular packing of the MUC5B mucin and the submucosal gland morphology creates an efficient machine for producing linear mucin bundles.
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| 20. |
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| 21. |
- Brismar, Torkel B., et al.
(författare)
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Magnetite Nanoparticles Can Be Coupled to Microbubbles to Support Multimodal Imaging
- 2012
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 13:5, s. 1390-1399
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Tidskriftsartikel (refereegranskat)abstract
- Microbubbles (MBs) are commonly used as injectable ultrasound contrast agent (UCA) in modern ultrasonography. Polymer-shelled UCAs present additional potentialities with respect to marketed lipid-shelled UCAs. They are more robust; that is, they have longer shelf and circulation life, and surface modifications are quite easily accomplished to obtain enhanced targeting and local drug delivery. The next generation of UCAs will be required to support not only ultrasound-based imaging methods but also other complementary diagnostic approaches such as magnetic resonance imaging or computer tomography. This work addresses the features of MBs that could function as contrast agents for both ultrasound and magnetic resonance imaging. The results indicate that the introduction of iron oxide nanoparticles (SPIONs) in the poly(vinyl alcohol) shell or on the external surface of the MBs does not greatly decrease the echogenicity of the host MBs compared with the unmodified one. The presence of SPIONs provides enough magnetic susceptibility to the MBs to accomplish good detectability both in vitro and in vivo. The distribution of SPIONs on the shell and their aggregation state seem to be key factors for the optimization of the transverse relaxation rate.
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| 22. |
- Busenlehner, Laura S., et al.
(författare)
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Location of substrate binding sites within the integral membrane protein microsomal glutathione transferase-1
- 2007
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 46:10, s. 2812-2822
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Tidskriftsartikel (refereegranskat)abstract
- Microsomal glutathione transferase-1 (MGST1) is a trimeric, membrane-bound enzyme with both glutathione (GSH) transferase and hydroperoxidase activities. As a member of the MAPEG superfamily, MGST1 aids in the detoxication of numerous xenobiotic substrates and in cellular protection from oxidative stress through the GSH-dependent reduction of phospholipid hydroperoxides. However, little is known about the location of the different substrate binding sites, including whether the transferase and peroxidase activities overlap structurally. Although molecular density attributed to GSH has been observed in the 3.2 A resolution electron crystallographic structure of MGST1, the electrophilic and phospholipid hydroperoxide substrate binding sites remain elusive. Amide H-D exchange kinetics and H-D ligand footprinting experiments indicate that GSH and hydrophobic substrates bind within similar, but distinct, regions of MGST1. Site-directed mutagenesis, guided by the H-D exchange results, demonstrates that specific residues within the GSH footprint effect transferase activity toward 1-chloro-2,4-dinitrobenzene. In addition, cytosolic residues surrounding the chemical stress sensor C49 but not modeled in the crystal structure appear to play an important role in the formation of the binding site for hydrophobic substrates. Although the fatty acid/phospholipid binding site structurally overlaps that for GSH, it does not appear to be localized to the same region as other hydrophobic substrates. Finally, H-D exchange mass spectrometry reveals a specific conformational transition that may mediate substrate binding and/or product release. Such structural changes in MGST1 are essential for activation of the enzyme and are important for its biological function.
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| 23. |
- Busenlehner, L.S., et al.
(författare)
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Stress sensor triggers conformational response of the integral membrane protein microsomal glutathione transferase 1
- 2004
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 43:35, s. 11145-11152
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Tidskriftsartikel (refereegranskat)abstract
- Microsomal glutathione (GSH) transferase 1 (MGST1) is a trimeric, integral membrane protein involved in cellular response to chemical or oxidative stress. The cytosolic domain of MGST1 harbors the GSH binding site and a cysteine residue (C49) that acts as a sensor of oxidative and chemical stress. Spatially resolved changes in the kinetics of backbone amide H/D exchange reveal that the binding of a single molecule of GSH/trimer induces a cooperative conformational transition involving movements of the transmembrane helices and a reordering of the cytosolic domain. Alkylation of the stress sensor preorganizes the helices and facilitates the cooperative transition resulting in catalytic activation.
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| 24. |
- Chabris, CF, et al.
(författare)
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Most reported genetic associations with general intelligence are probably false positives
- 2012
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Ingår i: Psychological science. - : SAGE Publications. - 1467-9280 .- 0956-7976. ; 23:11, s. 1314-1323
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Tidskriftsartikel (refereegranskat)abstract
- General intelligence ( g) and virtually all other behavioral traits are heritable. Associations between g and specific single-nucleotide polymorphisms (SNPs) in several candidate genes involved in brain function have been reported. We sought to replicate published associations between g and 12 specific genetic variants (in the genes DTNBP1, CTSD, DRD2, ANKK1, CHRM2, SSADH, COMT, BDNF, CHRNA4, DISC1, APOE, and SNAP25) using data sets from three independent, well-characterized longitudinal studies with samples of 5,571, 1,759, and 2,441 individuals. Of 32 independent tests across all three data sets, only 1 was nominally significant. By contrast, power analyses showed that we should have expected 10 to 15 significant associations, given reasonable assumptions for genotype effect sizes. For positive controls, we confirmed accepted genetic associations for Alzheimer’s disease and body mass index, and we used SNP-based calculations of genetic relatedness to replicate previous estimates that about half of the variance in g is accounted for by common genetic variation among individuals. We conclude that the molecular genetics of psychology and social science requires approaches that go beyond the examination of candidate genes.
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| 25. |
- Chen, G., et al.
(författare)
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Abilities of the BRICHOS domain to prevent neurotoxicity and fibril formation are dependent on a highly conserved Asp residue
- 2022
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Ingår i: RSC Chemical Biology. - : Royal Society of Chemistry (RSC). - 2633-0679. ; 3:11, s. 1342-1358
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Tidskriftsartikel (refereegranskat)abstract
- Proteins can self-assemble into amyloid fibrils or amorphous aggregates and thereby cause disease. Molecular chaperones can prevent both these types of protein aggregation, but to what extent the respective mechanisms are overlapping is not fully understood. The BRICHOS domain constitutes a disease-associated chaperone family, with activities against amyloid neurotoxicity, fibril formation, and amorphous protein aggregation. Here, we show that the activities of BRICHOS against amyloid-induced neurotoxicity and fibril formation, respectively, are oppositely dependent on a conserved aspartate residue, while the ability to suppress amorphous protein aggregation is unchanged by Asp to Asn mutations. The Asp is evolutionarily highly conserved in >3000 analysed BRICHOS domains but is replaced by Asn in some BRICHOS families. The conserved Asp in its ionized state promotes structural flexibility and has a pKa value between pH 6.0 and 7.0, suggesting that chaperone effects can be differently affected by physiological pH variations.
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| 26. |
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| 27. |
- Gardelle, J., et al.
(författare)
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High power electron beam interaction with an aluminum target : Measurements and simulations
- 2019
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 126:15
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Tidskriftsartikel (refereegranskat)abstract
- The study of the dynamic response of materials induced by electron beams requires precise knowledge of the beam when it interacts with the material. In this framework, the CESAR generator is used at CESTA. CESAR drives a field emission diode that delivers a single-shot intense electron pulse (approximate to 1MV, 300 kA, and 100 ns). The electron beam propagates into a gas-filled chamber where it is focused by a magnetic field onto an aluminum target. The analysis of the beam characteristics at the target position allows us to estimate the initial conditions required for precise hydrodynamic simulations. In this paper, we present the measurements of the electron beam characteristics. We paid particular attention to voltage, current, spatial homogeneity, dose rate, and incidence angles of electrons onto the target. Shocks induced in thin discs of aluminum are analyzed by using photon Doppler velocimetry, and the experimental data are compared with the predictions of simulations. Beam energy deposition is computed by using the 3D code Diane, and the hydrodynamic evolution of the target is performed with the code 2D/3D Hesione. Published under license by AIP Publishing.
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| 28. |
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| 29. |
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| 30. |
- Hong, Sanghee, et al.
(författare)
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Community health status and outcomes after allogeneic hematopoietic cell transplantation in the United States
- 2021
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Ingår i: Cancer. - : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 127:4, s. 609-618
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association of community factors and outcomes after hematopoietic cell transplantation (HCT) has not been comprehensively described. Using the County Health Rankings and Roadmaps (CHRR) and the Center for International Blood and Marrow Transplant Research (CIBMTR), this study evaluated the impact of community health status on allogeneic HCT outcomes.Methods: This study included 18,544 adult allogeneic HCT recipients reported to the CIBMTR by 170 US centers in 2014-2016. Sociodemographic, environmental, and community indicators were derived from the CHRR, an aggregate community risk score was created, and scores were assigned to each patient (patient community risk score [PCS]) and transplant center (center community risk score [CCS]). Higher scores indicated less healthy communities. The impact of PCS and CCS on patient outcomes after allogeneic HCT was studied.Results: The median age was 55 years (range, 18-83 years). The median PCS was -0.21 (range, -1.37 to 2.10; standard deviation [SD], 0.42), and the median CCS was -0.13 (range, -1.04 to 0.96; SD, 0.40). In multivariable analyses, a higher PCS was associated with inferior survival (hazard ratio [HR] per 1 SD increase, 1.04; 99% CI, 1.00-1.08;P= .0089). Among hematologic malignancies, a tendency toward inferior survival was observed with a higher PCS (HR, 1.04; 99% CI, 1.00-1.08;P= .0102); a higher PCS was associated with higher nonrelapse mortality (NRM; HR, 1.08; 99% CI, 1.02-1.15;P= .0004). CCS was not significantly associated with survival, relapse, or NRM.Conclusions: Patients residing in counties with a worse community health status have inferior survival as a result of an increased risk of NRM after allogeneic HCT. There was no association between the community health status of the transplant center location and allogeneic HCT outcomes.
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| 31. |
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| 32. |
- Kotova, Natalia, et al.
(författare)
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A novel micronucleus in vitro assay utilizing human hematopoietic stem cells
- 2015
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Ingår i: Toxicology in Vitro. - : Elsevier BV. - 0887-2333 .- 1879-3177. ; 29:7, s. 1897-1905
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Tidskriftsartikel (refereegranskat)abstract
- The induction of micronucleated reticulocytes in the bone marrow is a sensitive indicator of chromosomal damage. Therefore, the micronucleus assay in rodents is widely used in genotoxicity and carcinogenicity testing. A test system based on cultured human primary cells could potentially provide better prediction compared to animal tests, increasing patient safety while also implementing the 3Rs principle, i.e. replace, reduce and refine. Hereby, we describe the development of an in vitro micronucleus assay based on animal-free ex vivo culture of human red blood cells from hematopoietic stem cells. To validate the method, five clastogens with direct action, three clastogens requiring metabolic activation, four aneugenic and three non-genotoxic compounds have been tested. Also, different metabolic systems have been applied. Flow cytometry was used for detection and enumeration of micronuclei. Altogether, the results were in agreement with the published data and indicated that a sensitive and cost effective in vitro assay to assess genotoxicity with a potential to high-throughput screening has been developed.
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| 33. |
- Lancaster, D. G., et al.
(författare)
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An ultra-stable 2.9 mu m guided-wave chip laser and application to nano-spectroscopy
- 2019
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Ingår i: APL Photonics. - : AIP Publishing. - 2378-0967. ; 4:11
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Tidskriftsartikel (refereegranskat)abstract
- We present a configurable guided-wave planar glass-chip laser that produces low-noise and high-quality continuous-wave laser emission tunable from 2.82 to 2.95 mu m. The laser has a low threshold and intrinsic power and mode stability attributable to the high overlap of gain volume and pump mode defined by an ultrafast laser inscribed waveguide. The laser emission is single transverse-mode with a Gaussian spatial profile and M-x,y(2) similar to 1.05, 1.10. The power drift is similar to 0.08% rms over similar to 2 h. When configured in a spectrally free-running cavity, the guided-wave laser emits up to 170 mW. The benefit of low-noise and stable wavelength emission of this hydroxide resonant laser is demonstrated by acquiring high signal-to-noise images and spectroscopy of a corroded copper surface film with corrosion products containing water and hydroxide ions with a scattering-scanning near-field optical microscope.
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| 34. |
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| 35. |
- Loureiro, A., et al.
(författare)
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Size controlled protein nanoemulsions for active targeting of folate receptor positive cells
- 2015
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Ingår i: Colloids and Surfaces B. - : Elsevier. - 0927-7765 .- 1873-4367. ; 135, s. 90-98
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Tidskriftsartikel (refereegranskat)abstract
- Bovine serum albumin (BSA) nanoemulsions were produced by high pressure homogenization with a tri-block copolymer (Poloxamer 407), which presents a central hydrophobic chain of polyoxypropylene (PPO) and two identical lateral hydrophilic chains of polyethylene glycol (PEG). We observed a linear correlation between tri-block copolymer concentration and size - the use of 5. mg/mL of Poloxamer 407 yields nanoemulsions smaller than 100. nm. Molecular dynamics and fluorescent tagging of the tri-block copolymer highlight their mechanistic role on the size of emulsions. This novel method enables the fabrication of highly stable albumin emulsions in the nano-size range, highly desirable for controlled drug delivery. Folic Acid (FA)-tagged protein nanoemulsions were shown to promote specific folate receptor (FR)-mediated targeting in FR positive cells. The novel strategy presented here enables the construction of size controlled, functionalized protein-based nanoemulsions with excellent characteristics for active targeting in cancer therapy.
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| 36. |
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| 37. |
- Meng, Weihua, et al.
(författare)
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A genome-wide association study suggests new evidence for an association of the NADPH Oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes
- 2018
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X. ; 96:7, s. 811-819
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Diabetic retinopathy is the most common eye complication in patients with diabetes. The purpose of this study is to identify genetic factors contributing to severe diabetic retinopathy. Methods: A genome-wide association approach was applied. In the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) datasets, cases of severe diabetic retinopathy were defined as type 2 diabetic patients who were ever graded as having severe background retinopathy (Level R3) or proliferative retinopathy (Level R4) in at least one eye according to the Scottish Diabetic Retinopathy Grading Scheme or who were once treated by laser photocoagulation. Controls were diabetic individuals whose longitudinal retinopathy screening records were either normal (Level R0) or only with mild background retinopathy (Level R1) in both eyes. Significant Single Nucleotide Polymorphisms (SNPs) were taken forward for meta-analysis using multiple Caucasian cohorts. Results: Five hundred and sixty cases of type 2 diabetes with severe diabetic retinopathy and 4,106 controls were identified in the GoDARTS cohort. We revealed that rs3913535 in the NADPH Oxidase 4 (NOX4) gene reached a p value of 4.05 × 10−9. Two nearby SNPs, rs10765219 and rs11018670 also showed promising p values (p values = 7.41 × 10−8 and 1.23 × 10−8, respectively). In the meta-analysis using multiple Caucasian cohorts (excluding GoDARTS), rs10765219 and rs11018670 showed associations for diabetic retinopathy (p = 0.003 and 0.007, respectively), while the p value of rs3913535 was not significant (p = 0.429). Conclusion: This genome-wide association study of severe diabetic retinopathy suggests new evidence for the involvement of the NOX4 gene.
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| 38. |
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| 39. |
- Pascal, Mathilde M.V., et al.
(författare)
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DOLORisk : Study protocol for a multi-centre observational study to understand the risk factors and determinants of neuropathic pain [version 2; referees: 2 approved]
- 2019
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Ingår i: Wellcome Open Research. - : F1000 Research Ltd. - 2398-502X. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neuropathic pain is an increasingly prevalent condition and has a major impact on health and quality of life. However, the risk factors for the development and maintenance of neuropathic pain are poorly understood. Clinical, genetic and psychosocial factors all contribute to chronic pain, but their interactions have not been studied in large cohorts. The DOLORisk study aims to study these factors. Protocol: Multicentre cross-sectional and longitudinal cohorts covering the main causes leading to neuropathic pain (e.g. diabetes, surgery, chemotherapy, traumatic injury), as well as rare conditions, follow a common protocol for phenotyping of the participants. This core protocol correlates answers given by the participants on a set of questionnaires with the results of protocol for phenotyping of the participants. This core protocol correlates answers given by the participants on a set of questionnaires with the results of their genetic analyses. A smaller number of participants undergo deeper phenotyping procedures, including neurological examination, nerve conduction studies, threshold tracking, quantitative sensory testing, conditioned pain modulation and electroencephalography. Ethics and dissemination: All studies have been approved by their regional ethics committees as required by national law. Results are disseminated through the DOLORisk website, scientific meetings, open-access publications, and in partnership with patient organisations. Strengths and limitations: • Large cohorts covering many possible triggers for neuropathic pain • Multi-disciplinary approach to study the interaction of clinical, psychosocial and genetic risk factors • High comparability of the data across centres thanks to harmonised protocols • One limitation is that the length of the questionnaires might reduce the response rate and quality of responses of participants.
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| 40. |
- Poehlmann, Melanie, et al.
(författare)
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On the interplay of shell structure with low- and high-frequency mechanics of multifunctional magnetic microbubbles
- 2014
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 10:1, s. 214-226
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Tidskriftsartikel (refereegranskat)abstract
- Polymer-shelled magnetic microbubbles have great potential as hybrid contrast agents for ultrasound and magnetic resonance imaging. In this work, we studied US/MRI contrast agents based on air-filled poly(vinyl alcohol)-shelled microbubbles combined with superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs are integrated either physically or chemically into the polymeric shell of the microbubbles (MBs). As a result, two different designs of a hybrid contrast agent are obtained. With the physical approach, SPIONs are embedded inside the polymeric shell and with the chemical approach SPIONs are covalently linked to the shell surface. The structural design of hybrid probes is important, because it strongly determines the contrast agent's response in the considered imaging methods. In particular, we were interested how structural differences affect the shell's mechanical properties, which play a key role for the MBs' US imaging performance. Therefore, we thoroughly characterized the MBs' geometric features and investigated low-frequency mechanics by using atomic force microscopy (AFM) and high-frequency mechanics by using acoustic tests. Thus, we were able to quantify the impact of the used SPIONs integration method on the shell's elastic modulus, shear modulus and shear viscosity. In summary, the suggested approach contributes to an improved understanding of structure-property relations in US-active hybrid contrast agents and thus provides the basis for their sustainable development and optimization.
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| 41. |
- Porco, David, et al.
(författare)
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Biological invasions in soil: DNA barcoding as a monitoring tool in a multiple taxa survey targeting European earthworms and springtails in North America
- 2013
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Ingår i: Biological Invasions. - : Springer Science and Business Media LLC. - 1387-3547 .- 1573-1464. ; 15:4, s. 899-910
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Tidskriftsartikel (refereegranskat)abstract
- Biological invasions are increasingly recognized as a potent force altering native ecosystems worldwide. Many of the best documented cases involve the massive invasions of North America by plant and animal taxa native to Europe. In this study, we use DNA barcoding to survey the occurrence and genetic structure of two major groups of soil invertebrates in both their native and introduced ranges: Collembola and earthworms. Populations of ten species of earthworms and five species of Collembola were barcoded from both continents. Most of these species exhibited a similar genetic structure of large and stable populations in North America and Europe, a result supporting a scenario of multiple invasions. This was expected for earthworm species involved in human economic activities, but not foreseen for Collembola species de facto unintentionally introduced. This study also establishes that invasive species surveys employing DNA barcoding gain additional resolution over those based on morphology as they allow evaluation of cryptic lineages exhibiting different invasion histories.
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| 42. |
- Roslin, Tomas, et al.
(författare)
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A molecular-based identification resource for the arthropods of Finland
- 2022
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 22:2, s. 803-822
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Tidskriftsartikel (refereegranskat)abstract
- To associate specimens identified by molecular characters to other biological knowledge, we need reference sequences annotated by Linnaean taxonomy. In this study, we (1) report the creation of a comprehensive reference library of DNA barcodes for the arthropods of an entire country (Finland), (2) publish this library, and (3) deliver a new identification tool for insects and spiders, as based on this resource. The reference library contains mtDNA COI barcodes for 11,275 (43%) of 26,437 arthropod species known from Finland, including 10,811 (45%) of 23,956 insect species. To quantify the improvement in identification accuracy enabled by the current reference library, we ran 1000 Finnish insect and spider species through the Barcode of Life Data system (BOLD) identification engine. Of these, 91% were correctly assigned to a unique species when compared to the new reference library alone, 85% were correctly identified when compared to BOLD with the new material included, and 75% with the new material excluded. To capitalize on this resource, we used the new reference material to train a probabilistic taxonomic assignment tool, FinPROTAX, scoring high success. For the full-length barcode region, the accuracy of taxonomic assignments at the level of classes, orders, families, subfamilies, tribes, genera, and species reached 99.9%, 99.9%, 99.8%, 99.7%, 99.4%, 96.8%, and 88.5%, respectively. The FinBOL arthropod reference library and FinPROTAX are available through the Finnish Biodiversity Information Facility (www.laji.fi) at https://laji.fi/en/theme/protax. Overall, the FinBOL investment represents a massive capacity-transfer from the taxonomic community of Finland to all sectors of society.
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| 43. |
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| 44. |
- Wang, K, et al.
(författare)
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Long-term anti-inflammatory diet in relation to improved breast cancer prognosis: a prospective cohort study
- 2020
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1, s. 36-
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation-modulating nutrients and inflammatory markers are established cancer risk factors, however, evidence regarding the association between post-diagnosis diet-associated inflammation and breast cancer survival is relatively sparse. We aimed to examine the association between post-diagnosis dietary inflammatory index (DII®) and risks of all-cause and breast cancer-specific mortality. A total of 1064 female breast cancer survivors in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) Trial prospective cohort, were included in this analysis if they had completed the diet history questionnaire (DHQ). Energy-adjusted DII (E-DIITM) scores were calculated based on food and supplement intake. Cox regression and competing risk models were used to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (95% CIs) by E-DII tertile (T) for all-cause and breast cancer-specific mortality. With median follow-up of 14.6 years, there were 296 (27.8%) deaths from all causes and 100 (9.4%) breast cancer-specific death. The E-DII was associated with all-cause mortality (HR T3 vs T1, 1.34; 95% CI, 1.01–1.81; Ptrend, 0.049, Table 2) and breast cancer mortality (HR T3 vs T1, 1.47; 95% CI, 0.89–2.43; Ptrend, 0.13; multivariable-adjusted HR for 1-unit increment: 1.10; 95% CI: 1.00–1.22). Non-linear positive dose–response associations with mortality from all causes were identified for E-DII scores (Pnon-linearity < 0.05). The post-diagnosis E-DII was statistically significantly associated with mortality risk among breast cancer survivors. Long-term anti-inflammatory diet might be a means of improving survival of breast cancer survivors.
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| 45. |
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| 46. |
- Ålander, J., et al.
(författare)
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Microsomal glutathione transferase 1 exhibits one-third-of-the-sites-reactivity towards glutathione
- 2009
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Ingår i: Archives of Biochemistry and Biophysics. - : Elsevier BV. - 0003-9861 .- 1096-0384. ; 487:1, s. 42-48
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Tidskriftsartikel (refereegranskat)abstract
- The trimeric membrane protein microsomal glutathione transferase 1 (MGST1) possesses glutathione transferase and peroxidase activity. Previous data indicated one active site/trimer whereas structural data suggests three GSH-binding sites. Here we have determined ligand interactions of MGST1 by several techniques. Nanoelectrospray mass spectrometry of native MGST1 revealed binding of three GSH molecules/trimer and equilibrium dialysis showed three product molecules/trimer (K(d) = 320 +/- 50 mu M). All three product molecules Could be competed out with GSH. Reinvestigation of GSH-binding showed one high affinity site per trimer, consistent with earlier data. Using single turnover stopped flow kinetic measurements, Kd could be determined for a low affinity GSH-binding site (2.5 +/- 0.5 mu M). Thus we can reconcile previous observations and show here that MGST1 contains three active sites with different affinities for GSH and that only the high affinity site is catalytically competent.
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