Publications by authors named "B Nilsson"

1,899 Publications

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Numerical modeling of nitrate removal in anoxic groundwater during river flooding of riparian zones.

Ground Water 2021 May 3. Epub 2021 May 3.

Department of Geosciences and Natural Resource Management, Section of Geology, University of Copenhagen, Øster Voldgade 10, 1350, Copenhagen K, Denmark.

A numerical study demonstrates the effects of flooding on subsurface hydrological flow paths and nitrate removal in anoxic groundwater in riparian zones with a top peat layer. A series of 2D numerical simulations with changing conditions for flow (steady state or transient with flooding), hydrogeology, denitrification, and duration of flooding demonstrate how flow paths, residence times, and nitrate removal are affected. In periods with no flooding groundwater flows horizontally and discharges to the river through the riverbed. During periods with flooding, shallow groundwater is forced upwards as discharge through peat layers that often have more optimal conditions for denitrification caused by the presence of highly reactive organic matter. The contrast in hydraulic conductivity between the sand aquifer and the overlying peat layer, as well as the flooding duration, have a significant role in determining the degree of nitrate removal. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/gwat.13108DOI Listing
May 2021

Hemocompatibility of Nanotitania-Nanocellulose Hybrid Materials.

Nanomaterials (Basel) 2021 Apr 24;11(5). Epub 2021 Apr 24.

Rudbeck Laboratory C5:3, Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden.

In order to develop a new type of improved wound dressing, we combined the wound healing properties of nanotitania with the advantageous dressing properties of nanocellulose to create three different hybrid materials. The hemocompatibility of the synthesized hybrid materials was evaluated in an in vitro human whole blood model. To our knowledge, this is the first study of the molecular interaction between hybrid nanotitania and blood proteins. Two of the hybrid materials prepared with 3 nm colloidal titania and 10 nm hydrothermally synthesized titania induced strong coagulation and platelet activation but negligible complement activation. Hence, they have great potential as a new dressing for promoting wound healing. Unlike the other two, the third hybrid material using molecular ammonium oxo-lactato titanate as a titania source inhibited platelet consumption, TAT generation, and complement activation, apparently via lowered pH at the surface interface. It is therefore suitable for applications where a passivating surface is desired, such as drug delivery systems and extracorporeal circuits. This opens the possibility for a tailored blood response through the surface functionalization of titania.
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http://dx.doi.org/10.3390/nano11051100DOI Listing
April 2021

Defining the Landscape of the Pauling-Corey Rippled Sheet: An Orphaned Motif Finding New Homes.

Acc Chem Res 2021 Apr 26. Epub 2021 Apr 26.

Department of Chemistry, University of Rochester, Rochester, New York 14627-0216, United States.

ConspectusWhen peptides are mixed with their mirror images in an equimolar ratio, two-dimensional periodic structural folds can form, in which extended peptide strands are arrayed with alternating chirality. The resultant topography class, termed the rippled β-sheet, was introduced as a theoretical concept by Pauling and Corey in 1953. Unlike other fundamental protein structural motifs identified around that time, including the α-helix and the pleated β-sheet, it took several decades before conclusive experimental data supporting the proposed rippled β-sheet motif were gained. Much of the key experimental evidence was provided over the course of the past decade through the concurrent efforts of our three laboratories. Studies that focused on developing new self-assembling hydrogel materials have shown that certain amphiphilic peptides form fibrils and hydrogel networks that are more rigid and have a higher thermodynamic stability when made from racemic peptide mixtures as opposed to pure enantiomers. Related interrogation of assemblies composed of mixtures of l- and d-amphiphilic peptides confirmed that the resulting fibrils were composed of alternating l/d peptides consistent with rippled β-sheets. It was also demonstrated that mirror-image amyloid beta (Aβ) could act as a molecular chaperone to promote oligomer-to-fibril conversion of the natural Aβ enantiomer, which was found to reduce Aβ neurotoxicity against different neuronal cell models. With a cross-disciplinary approach that combines experiment and theory, our three laboratories have demonstrated the unique biophysical, biochemical, and biological properties that arise upon mixing of peptide enantiomers, in consequence of rippled β-sheet formation. In this Account, we give an overview of the early history of the rippled β-sheet and provide a detailed structural description/definition of this motif relative to the pleated β-sheet. We then summarize the key findings, obtained on three unique sets of aggregating mirror-image peptide pairs through independent efforts of our three laboratories, and use these results to delineate the landscape of the rippled β-sheet structural motif to inspire future studies. Peptide sequence parameters that favor rippled β-sheet assembly are described, along with the accompanying kinetic and thermodynamic properties, as well as the resulting emergent physical properties of the assemblies. The Account then concludes with a brief overview of some key unresolved challenges in this nascent field. There is much potential for future applications of this unique supramolecular motif in the realm of materials design and biomedical research. We hope this Account will stimulate much-needed discussion of this fascinating structural class to eventually produce a fully quantitative, rational framework for the molecular engineering of rippled β-sheets in the future.
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http://dx.doi.org/10.1021/acs.accounts.1c00084DOI Listing
April 2021

Germline variants at SOHLH2 influence multiple myeloma risk.

Blood Cancer J 2021 Apr 19;11(4):76. Epub 2021 Apr 19.

Hematology and Transfusion Medicine, Department of Laboratory Medicine, 221 84, Lund, Sweden.

Multiple myeloma (MM) is caused by the uncontrolled, clonal expansion of plasma cells. While there is epidemiological evidence for inherited susceptibility, the molecular basis remains incompletely understood. We report a genome-wide association study totalling 5,320 cases and 422,289 controls from four Nordic populations, and find a novel MM risk variant at SOHLH2 at 13q13.3 (risk allele frequency = 3.5%; odds ratio = 1.38; P = 2.2 × 10). This gene encodes a transcription factor involved in gametogenesis that is normally only weakly expressed in plasma cells. The association is represented by 14 variants in linkage disequilibrium. Among these, rs75712673 maps to a genomic region with open chromatin in plasma cells, and upregulates SOHLH2 in this cell type. Moreover, rs75712673 influences transcriptional activity in luciferase assays, and shows a chromatin looping interaction with the SOHLH2 promoter. Our work provides novel insight into MM susceptibility.
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http://dx.doi.org/10.1038/s41408-021-00468-6DOI Listing
April 2021

Interleukin 8 Elicits Rapid Physiological Changes in Neutrophils That Are Altered by Inflammatory Conditions.

J Innate Immun 2021 Apr 15:1-17. Epub 2021 Apr 15.

Institute of Clinical and Experimental Trauma Immunology, University Hospital of Ulm, Ulm, Germany.

A sufficient response of neutrophil granulocytes stimulated by interleukin (IL)-8 is vital during systemic inflammation, for example, in sepsis or severe trauma. Moreover, IL-8 is clinically used as biomarker of inflammatory processes. However, the effects of IL-8 on cellular key regulators of neutrophil properties such as the intracellular pH (pHi) in dependence of ion transport proteins and during inflammation remain to be elucidated. Therefore, we investigated in detail the fundamental changes in pHi, cellular shape, and chemotactic activity elicited by IL-8. Using flow cytometric methods, we determined that the IL-8-induced cellular activity was largely dependent on specific ion channels and transporters, such as the sodium-proton exchanger 1 (NHE1) and non-NHE1-dependent sodium flux. Exposing neutrophils in vitro to a proinflammatory micromilieu with N-formyl-Met-Leu-Phe, LPS, or IL-8 resulted in a diminished response regarding the increase in cellular size and pH. The detailed kinetics of the reduced reactivity of the neutrophil granulocytes could be illustrated in a near-real-time flow cytometric measurement. Last, the LPS-mediated impairment of the IL-8-induced response in neutrophils was confirmed in a translational, animal-free human whole blood model. Overall, we provide novel mechanistic insights for the interaction of IL-8 with neutrophil granulocytes and report in detail about its alteration during systemic inflammation.
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http://dx.doi.org/10.1159/000514885DOI Listing
April 2021