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- Abikhodr, A. H., et al.
(författare)
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Identifying Mixtures of Isomeric Human Milk Oligosaccharides by the Decomposition of IR Spectral Fingerprints
- 2021
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 93:44, s. 14730-14736
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Tidskriftsartikel (refereegranskat)abstract
- The analysis of glycans presents a significant challenge that arises from their isomeric heterogeneity. While high-resolution ion mobility spectrometry (IMS) has shown the ability to resolve subtly different glycan isomers, their unambiguous assignment remains difficult. Here, we demonstrate an infrared (IR) spectroscopic approach for identifying isomers in a glycan mixture. To display the feasibility of this approach, we have constructed a small database of cryogenic spectra of five lacto-N-fucopentaose (LNFP) and six disaccharide isomers and demonstrated that in the cases where they cannot be separated by IMS, we can use a cryogenic IR spectrum to identify the isomeric components of a mixture.
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- Bansal, P., et al.
(författare)
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Using SLIM-Based IMS-IMS Together with Cryogenic Infrared Spectroscopy for Glycan Analysis
- 2020
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 92:13, s. 9079-9085
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Tidskriftsartikel (refereegranskat)abstract
- The isomeric heterogeneity of glycans poses a great challenge for their analysis. While combining ion mobility spectrometry (IMS) with tandem mass spectrometry is a powerful means for identifying and characterizing glycans, it has difficulty distinguishing the subtlest differences between isomers. Cryogenic infrared spectroscopy provides an additional dimension for glycan identification that is extremely sensitive to their structure. Our approach to glycan analysis combines ultrahigh-resolution IMS-IMS using structures for lossless ion manipulation (SLIM) with cryogenic infrared spectroscopy. We present here the design of a SLIM board containing a series of on-board traps in which we perform collision-induced dissociation (CID) at pressures in the millibar range. We characterize the on-board CID process by comparing the fragments generated from a pentapeptide to those obtained on a commercial tandem mass spectrometer. We then apply our new technique to study the mobility and vibrational spectra of CID fragments from two human milk oligosaccharides. Comparison of both the fragment drift times and IR spectra with those of suitable reference compounds allows us to identify their specific isomeric form, including the anomericity of the glycosidic linkage, demonstrating the power of this tool for glycan analysis. Copyright © 2020 American Chemical Society.
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- Fountoulakis, KN, et al.
(författare)
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Relationship of suicide rates to economic variables in Europe: 2000-2011
- 2014
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Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 205:6, s. 486-496
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Tidskriftsartikel (refereegranskat)abstract
- It is unclear whether there is a direct link between economic crises and changes in suicide rates.AimsThe Lopez-Ibor Foundation launched an initiative to study the possible impact of the economic crisis on European suicide rates.MethodData was gathered and analysed from 29 European countries and included the number of deaths by suicide in men and women, the unemployment rate, the gross domestic product (GDP) per capita, the annual economic growth rate and inflation.ResultsThere was a strong correlation between suicide rates and all economic indices except GPD per capita in men but only a correlation with unemployment in women. However, the increase in suicide rates occurred several months before the economic crisis emerged.ConclusionsOverall, this study confirms a general relationship between the economic environment and suicide rates; however, it does not support there being a clear causal relationship between the current economic crisis and an increase in the suicide rate.
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- Schumacher, J, et al.
(författare)
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Linkage analyses of chromosomal region 18p11-q12 in dyslexia
- 2006
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Ingår i: Journal of neural transmission. - Vienna, Austria : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 113:3, s. 417-23
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Tidskriftsartikel (refereegranskat)abstract
- Dyslexia is characterized as a significant impairment in reading and spelling ability that cannot be explained by low intelligence, low school attendance or deficits in sensory acuity. It is known to be a hereditary disorder that affects about 5% of school aged children, making it the most common of childhood learning disorders. Several susceptibility loci have been reported on chromosomes 1, 2, 3, 6, 15, and 18. The locus on chromosome 18 has been described as having the strongest influence on single word reading, phoneme awareness, and orthographic coding in the largest genome wide linkage study published to date (Fisher et al., 2002). Here we present data from 82 German families in order to investigate linkage of various dyslexia-related traits to the previously described region on chromosome 18p11-q12. Using two- and multipoint analyses, we did not find support for linkage of spelling, single word reading, phoneme awareness, orthographic coding and rapid naming to any of the 14 genotyped STR markers. Possible explanations for our non-replication include differences in study design, limited power of our study and overestimation of the effect of the chromosome 18 locus in the original study.
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- Warnke, C., et al.
(författare)
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Changes to anti-JCV antibody levels in a Swedish national MS cohort
- 2013
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 84:11, s. 1199-1205
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Tidskriftsartikel (refereegranskat)abstract
- Background The anti-JC virus (JCV) antibody status has been introduced to stratify patients with multiple sclerosis (MS) for higher or lower risk of progressive multifocal leukoencephalopathy (PML). Objective To assess the potential utility of anti-JCV antibody levels for earlier diagnosis or prediction of PML. Methods An analytically validated antibody assay was used to determine serological status, normalised optical density values, and dilution titres for anti-JCV antibodies. The method was applied to stored sera of 1157 patients with MS including five cases of PML, all enrolled in the Swedish pharmacovigilance study for natalizumab (NAT). Anticytomegalovirus (CMV) and antivaricella-zoster (VZV) antibody levels served as controls. Results Prior to treatment with NAT, anti-JCV antibody levels were stable in the anti-JCV positive patients. During therapy, a slight decrease in anti-JCV and anti-VZV antibody levels, but not anti-CMV antibody levels, was observed. All five patients who developed PML showed a mild to moderate increase in anti-JCV antibody levels at time of PML diagnosis; pre-PML samples suggested that this increase might start already prior to diagnosis of PML. Conclusions Treatment initiation with NAT may lead to a slight decrease in anti-JCV and anti-VZV antibody levels, suggestive of a mild suppressive effect of NAT on antibody levels. Our findings in five cases of PML demonstrate that the onset of PML can be accompanied by increasing anti-JCV antibodies in serum. Monitoring of anti-JCV antibody levels could potentially be used as a tool for prediction or earlier diagnosis of PML during NAT treatment for MS. Further studies are warranted.
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| 17. |
- Yatsyna, Vasyl, et al.
(författare)
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High-Throughput Multiplexed Infrared Spectroscopy of Ion Mobility-Separated Species Using Hadamard Transform
- 2022
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 94:6, s. 2912-2917
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Tidskriftsartikel (refereegranskat)abstract
- Coupling vibrational ion spectroscopy with highresolution ion mobility separation offers a promising approach for detailed analysis of biomolecules in the gas phase. Improvements in the ion mobility technology have made it possible to separate isomers with minor structural differences, and their interrogation with a tunable infrared laser provides vibrational fingerprints for unambiguous database-enabled identification. Nevertheless, wide analytical application of this technique requires high-throughput approaches for acquisition of vibrational spectra of all species present in complex mixtures. In this work, we present a novel multiplexed approach and demonstrate its utility for cryogenic ion spectroscopy of peptides and glycans in mixtures. Since the method is based on Hadamard transform multiplexing, it yields infrared spectra with an increased signal-to-noise ratio compared to a conventional signal averaging approach.
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| 19. |
- Dorschel, Boris, et al.
(författare)
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The International Bathymetric Chart of the Southern Ocean Version 2
- 2022
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The Southern Ocean surrounding Antarctica is a region that is key to a range of climatic and oceanographic processes with worldwide effects, and is characterised by high biological productivity and biodiversity. Since 2013, the International Bathymetric Chart of the Southern Ocean (IBCSO) has represented the most comprehensive compilation of bathymetry for the Southern Ocean south of 60 degrees S. Recently, the IBCSO Project has combined its efforts with the Nippon Foundation - GEBCO Seabed 2030 Project supporting the goal of mapping the world's oceans by 2030. New datasets initiated a second version of IBCSO (IBCSO v2). This version extends to 50 degrees S (covering approximately 2.4 times the area of seafloor of the previous version) including the gateways of the Antarctic Circumpolar Current and the Antarctic circumpolar frontal systems. Due to increased (multibeam) data coverage, IBCSO v2 significantly improves the overall representation of the Southern Ocean seafloor and resolves many submarine landforms in more detail. This makes IBCSO v2 the most authoritative seafloor map of the area south of 50 degrees S.
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| 20. |
- Dyukova, I., et al.
(författare)
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A new approach for identifying positional isomers of glycans cleaved from monoclonal antibodies
- 2021
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Ingår i: Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654. ; 146:15, s. 4789-4795
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Tidskriftsartikel (refereegranskat)abstract
- Glycosylation patterns in monoclonal antibodies (mAbs) can vary significantly between different host cell types, and these differences may affect mAbs safety, efficacy, and immunogenicity. Recent studies have demonstrated that glycan isomers with the terminal galactose position on either the Man alpha 1-3 arm or the Man alpha 1-6 arm have an impact on the effector functions and dynamic structure of mAbs. The development of a robust method to distinguish positional isomers of glycans is thus critical to guarantee mAb quality. In this work, we apply high-resolution ion mobility combined with cryogenic infrared spectroscopy to distinguish isomeric glycans with different terminal galactose positions, using G1F as an example. Selective enzymatic synthesis of the G1(alpha 1-6)F isomer allows us to assign the peaks in the arrival-time distributions and the infrared spectra to their respective isomeric forms. Moreover, we demonstrate the impact of the host cell line (CHO and HEK-293) on the IgG G1F gycan profile at the isomer level. This work illustrates the potential of our approach for glycan analysis of mAbs.
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| 22. |
- Persson Berg, Linn, 1984, et al.
(författare)
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Serum IgG levels to Epstein-Barr and measles viruses in patients with multiple sclerosis during natalizumab and interferon beta treatment
- 2022
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Ingår i: Bmj Neurology Open. - : BMJ. - 2632-6140. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with multiple sclerosis (MS) demonstrate higher seroprevalence of Epstein-Barr virus (EBV) and increased anti-EBV IgG levels in serum compared with healthy controls. Intrathecal antibody production to measles virus (MeV) is a common finding in patients with MS. Objective To measure serum IgG reactivity to EBV glycoprotein 350 (gp350) and MeV nucleocapsid protein (N-CORE) in patients with MS and healthy controls and to determine if reactivity changed in patients during interferon beta (IFN beta) and/or natalizumab (NAT) treatment. A secondary aim was to determine the seroprevalence of EBV in patients and controls. Methods Patients with MS (n=728) were included from the Swedish pharmacovigilance study for NAT. Paired serum samples from 714 patients drawn before and during NAT treatment and paired samples from 170 patients during prior IFN beta treatment were analysed. In total, 156 patients were included in both groups. Samples from 144 matched blood donors served as controls. Indirect ELISA was applied using recombinant EBVgp350 and MeV N-CORE as antigens. EBVgp350 IgG seronegative samples were also analysed using EBV nuclear antigen 1 and viral capsid antigen (VCA). Results Patients with MS showed higher serum levels of anti-EBVgp350 and anti-MeV N-CORE IgG compared with controls. During NAT treatment, the levels of anti-EBVgp350 and anti-MeV N-CORE IgG declined, compared with the relatively stable levels noted during prior IFN beta treatment. Ten patients failed to demonstrate anti-EBVgp350 IgG but did show detectable anti-VCA IgG, indicating EBV seropositivity. In contrast, 10/144 controls were EBV seronegative. Conclusions Treatment with NAT, which is considered a selective immunosuppressive agent with a compartmentalised effect on the central nervous system, appeared to be associated with a moderate decrease in circulating IgG levels to EBVgp350 and MeV N-CORE. All patients with MS were EBV IgG seropositive, supporting the potential role of EBV in the pathogenesis of MS.
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