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Sökning: WFRF:(Nilsson Mats) > Stockholms universitet

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1.
  • Ayoglu, Burcu, et al. (författare)
  • Multiplexed protein profiling by sequential affinity capture
  • 2016
  • Ingår i: Proteomics. - : Wiley-Blackwell. - 1615-9853 .- 1615-9861. ; 16:8, s. 1251-1256
  • Tidskriftsartikel (refereegranskat)abstract
    • Antibody microarrays enable parallelized and miniaturized analysis of clinical samples, and have proven to provide novel insights for the analysis of different proteomes. However, there are concerns that the performance of such direct labeling and single antibody assays are prone to off-target binding due to the sample context. To improve selectivity and sensitivity while maintaining the possibility to conduct multiplexed protein profiling, we developed a multiplexed and semi-automated sequential capture assay. This novel bead-based procedure encompasses a first antigen capture, labeling of captured protein targets on magnetic particles, combinatorial target elution and a read-out by a secondary capture bead array. We demonstrate in a proof-of-concept setting that target detection via two sequential affinity interactions reduced off-target contribution, while lowered background and noise levels, improved correlation to clinical values compared to single binder assays. We also compared sensitivity levels with single binder and classical sandwich assays, explored the possibility for DNA-based signal amplification, and demonstrate the applicability of the dual capture bead-based antibody microarray for biomarker analysis. Hence, the described concept enhances the possibilities for antibody array assays to be utilized for protein profiling in body fluids and beyond.
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2.
  • Bluhm, Gösta, et al. (författare)
  • Buller.
  • 2006
  • Ingår i: Barns hälsa och miljö i Stockholms län 2006. - : Stockholms läns landsting, Stockholm. - 9163190230 ; , s. 113-126
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Noise is an environmental problem that affects children both at school and home. This chapter summarizes the results on noise disturbances from the “Children’s environment and health survey” conducted in Stockholm County in year 2003. It was found that children were most disturbed by noise at school. Thirty per cent of all 8- and 12 year old children in Stockholm County were annoyed by noise at school, mainly noise from other children. Children in Stockholm County were exposed to more noise in their homes than children in other parts of Sweden. Almost 50 % of children in inner city Stockholm and 20 % in the rest of the County were living in apartments with windows facing a major road, railway or industry. Eighteen per cent of all 8- and 12-year olds were disturbed by noise in their homes. Slightly less than 6 % reports that noise disturbed school homework or speech communication, whereas 4 % reported difficulties in falling asleep due to noise in the home. Approximately three per cent of parents to all 4-, 8- and 12-year old children reported that their children have reduced hearing, and three per cent of 8- and 12-year old children reported that they have tinnitus. It is concluded that noise in dwellings and schools should be reduced in order to provide good and healthy sound environments for children. Furthermore, the sound environment should be considered already at the planning stage, in order to minimize indoor and outdoor noise exposure in future dwellings and schools.
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4.
  • Ch'ng, Jun-Hong, et al. (författare)
  • Epitopes of anti-RIFIN antibodies and characterization of rif-expressing Plasmodium falciparum parasites by RNA sequencing
  • 2017
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Variable surface antigens of Plasmodium falciparum have been a major research focus since they facilitate parasite sequestration and give rise to deadly malaria complications. Coupled with its potential use as a vaccine candidate, the recent suggestion that the repetitive interspersed families of polypeptides (RIFINs) mediate blood group A rosetting and influence blood group distribution has raised the research profile of these adhesins. Nevertheless, detailed investigations into the functions of this highly diverse multigene family remain hampered by the limited number of validated reagents. In this study, we assess the specificities of three promising polyclonal anti-RIFIN antibodies that were IgG-purified from sera of immunized animals. Their epitope regions were mapped using a 175,000-peptide microarray holding overlapping peptides of the P. falciparum variable surface antigens. Through immunoblotting and immunofluorescence imaging, we show that different antibodies give varying results in different applications/assays. Finally, we authenticate the antibody-based detection of RIFINs in two previously uncharacterized non-rosetting parasite lines by identifying the dominant rif transcripts using RNA sequencing.
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5.
  • Ehnvall, Betty, et al. (författare)
  • Catchment characteristics control boreal mire nutrient regime and vegetation patterns over ~5000 years of landscape development
  • 2023
  • Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 895
  • Tidskriftsartikel (refereegranskat)abstract
    • Vegetation holds the key to many properties that make natural mires unique, such as surface microtopography, high biodiversity values, effective carbon sequestration and regulation of water and nutrient fluxes across the landscape. Despite this, landscape controls behind mire vegetation patterns have previously been poorly described at large spatial scales, which limits the understanding of basic drivers underpinning mire ecosystem services. We studied catchment controls on mire nutrient regimes and vegetation patterns using a geographically constrained natural mire chronosequence along the isostatically rising coastline in Northern Sweden. By comparing mires of different ages, we can partition vegetation patterns caused by long-term mire succession (<5000 years) and present-day vegetation responses to catchment eco-hydrological settings. We used the remote sensing based normalized difference vegetation index (NDVI) to describe mire vegetation and combined peat physicochemical measures with catchment properties to identify the most important factors that determine mire NDVI. We found strong evidence that mire NDVI depends on nutrient inputs from the catchment area or underlying mineral soil, especially concerning phosphorus and potassium concentrations. Steep mire and catchment slopes, dry conditions and large catchment areas relative to mire areas were associated with higher NDVI. We also found long-term successional patterns, with lower NDVI in older mires. Importantly, the NDVI should be used to describe mire vegetation patterns in open mires if the focus is on surface vegetation, since the canopy cover in tree-covered mires completely dominated the NDVI signal. With our study approach, we can quantitatively describe the connection between landscape properties and mire nutrient regime. Our results confirm that mire vegetation responds to the upslope catchment area, but importantly, also suggest that mire and catchment aging can override the role of catchment influence. This effect was clear across mires of all ages, but was strongest in younger mires.
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6.
  • Hernández-Neuta, Iván, 1986-, et al. (författare)
  • Highly multiplexed targeted sequencing strategy for infectious disease surveillance
  • 2023
  • Ingår i: BMC Biotechnology. - 1472-6750. ; 23
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Global efforts to characterize diseases of poverty are hampered by lack of affordable and comprehensive detection platforms, resulting in suboptimal allocation of health care resources and inefficient disease control. Next generation sequencing (NGS) can provide accurate data and high throughput. However, shotgun and metagenome-based NGS approaches are limited by low concentrations of microbial DNA in clinical samples, requirements for tailored sample and library preparations plus extensive bioinformatics analysis. Here, we adapted molecular inversion probes (MIPs) as a cost-effective target enrichment approach to characterize microbial infections from blood samples using short-read sequencing. We designed a probe panel targeting 2 bacterial genera, 21 bacterial and 6 fungi species and 7 antimicrobial resistance markers (AMRs).Results Our approach proved to be highly specific to detect down to 1 in a 1000 pathogen DNA targets contained in host DNA. Additionally, we were able to accurately survey pathogens and AMRs in 20 out of 24 samples previously profiled with routine blood culture for sepsis.Conclusions Overall, our targeted assay identifies microbial pathogens and AMRs with high specificity at high throughput, without the need for extensive sample preparation or bioinformatics analysis, simplifying its application for characterization and surveillance of infectious diseases in medium- to low- resource settings.
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7.
  • Lasaviciute, Gintare, et al. (författare)
  • Epstein-Barr Virus, but Not Cytomegalovirus, Latency Accelerates the Decay of Childhood Measles and Rubella Vaccine Responses-A 10-Year Follow-up of a Swedish Birth Cohort
  • 2017
  • Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are ubiquitous and persistent herpesviruses commonly acquired during childhood. Both viruses have a significant impact on the immune system, especially through mediating the establishment of cellular immunity, which keeps these viruses under control for life. Far less is known about how these viruses influence B-cell responses. Objectives: To evaluate the impact of latent EBV and CMV infection on rubella- and measles-specific antibody responses as well as on the B-cell compartment in a prospective birth cohort followed during the first 10 years of life. Methods: IgG titers against rubella and measles vaccines were measured in plasma obtained from the same donors at 2, 5, and 10 years of age. Peripheral B-cell subsets were evaluated ex vivo at 2 and 5 years of age. Factors related to optimal B-cell responses including IL-21 and CXCL13 levels in plasma were measured at all-time points. Results: EBV carriage in the absence of CMV associated with an accelerated decline of rubella and measles-specific IgG levels (p = 0.003 and p = 0.019, respectively, linear mixed model analysis), while CMV carriage in the absence of EBV associated with delayed IgG decay over time for rubella (p = 0.034). At 5 years of age, EBV but not CMV latency associated with a lower percentage of plasmablasts, but higher IL-21 levels in the circulation. Conclusion: Our findings suggest that EBV carriage in the absence of CMV influences the B-cell compartment and the dynamics of antibody responses over time during steady state in the otherwise healthy host.
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8.
  • Mansouri, Larry, et al. (författare)
  • Functional loss of I kappa B epsilon leads to NF-kappa B deregulation in aggressive chronic lymphocytic leukemia
  • 2015
  • Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 212:6, s. 833-843
  • Tidskriftsartikel (refereegranskat)abstract
    • NF-kappa B is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-kappa B pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes I kappa B epsilon, a negative regulator of NF-kappa B in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced I kappa B epsilon protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that I kappa B epsilon loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-kappa B deregulation during lymphomagenesis.
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9.
  • Osterwalder, S., et al. (författare)
  • Critical Observations of Gaseous Elemental Mercury Air-Sea Exchange
  • 2021
  • Ingår i: Global Biogeochemical Cycles. - : American Geophysical Union (AGU). - 0886-6236 .- 1944-9224. ; 35:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Air-sea exchange of gaseous elemental mercury (Hg-0) is not well constrained, even though it is a major component of the global Hg cycle. Lack of Hg-0 flux measurements to validate parameterizations of the Hg-0 transfer velocity contributes to this uncertainty. We measured the Hg-0 flux on the Baltic Sea coast using micrometeorological methods (gradient-based and relaxed eddy accumulation [REA]) and also simulated the flux with a gas exchange model. The coastal waters were typically supersaturated with Hg-0 (mean +/- 1 sigma = 13.5 +/- 3.5 ng m(-3); ca. 10% of total Hg) compared to the atmosphere (1.3 +/- 0.2 ng m(-3)). The Hg-0 flux calculated using the gas exchange model ranged from 0.1-1.3 ng m(-2) h(-1) (10th and 90th percentile) over the course of the campaign (May 10-June 20, 2017) and showed a distinct diel fluctuation. The mean coastal Hg-0 fluxes determined with the two gradient-based approaches and REA were 0.3, 0.5, and 0.6 ng m(-2) h(-1), respectively. In contrast, the mean open sea Hg-0 flux measured with REA was larger (6.3 ng m(-2) h(-1)). The open sea Hg-0 flux indicated a stronger wind speed dependence for the Hg-0 transfer velocity compared to commonly used parameterizations. Although based on a limited data set, we suggest that the wind speed dependence of the Hg-0 transfer velocity is more consistent with gases that have less water solubility than CO2 (e.g., O-2). These pioneering flux measurements using micrometeorological techniques show that more such measurements would improve our understanding of air-sea Hg exchange.
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10.
  • Ruiz-Moreno, Cristian, et al. (författare)
  • Harmonized single-cell landscape, tumor architecture, and intercellular crosstalk ofIDH-wildtype glioblastoma
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Glioblastoma, isocitrate dehydrogenase (IDH)-wildtype (hereafter, GB), is an aggressivebrain malignancy associated with a dismal prognosis and poor quality of life. Single-cellRNA sequencing has aided in grasping the complexity of the cell states and dynamic changesin GB. Large-scale data integration can help to uncover unexplored tumor pathobiology.Here, we resolved the composition of the tumor milieu and created a cellular map of GB(‘GBmap’), a curated resource that harmonizes 26 datasets, gathering 240 patients andspanning over 1.1 million cells. We showcase the applications of our resource for referencemapping, transfer learning, and biological discoveries. Reconstructing the tumor architectureusing spatially resolved transcriptomics unveiled consistent niches across patients and theirorganizational gradient. Our findings shed light on specific crosstalk within GB niches,including the intricate proangiogenic signaling. The GBmap represents a framework thatallows the streamlined integration and interpretation of new data and provides a platform forexploratory analysis, hypothesis generation, and testing.
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