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1.
  • Bonde, J. P. E., et al. (author)
  • Occupational risk of COVID-19 across pandemic waves: a two-year national follow-up study of hospital admissions
  • 2022
  • In: Scandinavian Journal of Work Environment & Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 48:8, s. 672-677
  • Journal article (peer-reviewed)abstract
    • Objective Assuming that preventive measures to mitigate viral transmission of SARS-CoV-2 at the workplace may have been improved in the course of the COVID-19 pandemic, we examined the occupational risk of COVID-19 related hospital admission across the four pandemic waves in Denmark between week 8, 2020, and week 50, 2021. Methods The study included 4416 cases of COVID-19 related hospital admissions among 2.4 million Danish employees aged 20-69 with follow-up in 2020 through 2021. At-risk industrial sectors and a reference population were defined a priory by a job-exposure matrix on occupational risk for COVID-19. Incidence rate ratios (IRR) and potential effect modification by pandemic wave were computed with Poisson regression adjusted for demographic, social and health factors including completed COVID-19 vaccination. Results We observed an overall elevated relative risk in four of six at-risk industrial sectors, but the pandemic wave only modified the risk among healthcare employees, where the excess risk from a high initial level declined to background levels during the latest waves in models not adjusting for COVID-19 vaccination. In social care, education and transport, the elevated risk was not modified by pandemic wave. Conclusion Danish healthcare employees were to some extent protected against occupational transmission of SARS-CoV-2 during the two last pandemic waves even though the absolute risk conferred by occupation may not have been eliminated. Early vaccination of this group seems not to be the only explanation. The risk in other sectors remained elevated indicating a need to revisit preventive measures.
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2.
  • Orikiiriza, Judy, et al. (author)
  • Lipid response patterns in acute phase paediatric Plasmodium falciparum malaria
  • 2017
  • In: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 13:4
  • Journal article (peer-reviewed)abstract
    • Introduction: Several studies have observed serum lipid changes during malaria infection in humans. All of them were focused at analysis of lipoproteins, not specific lipid molecules. The aim of our study was to identify novel patterns of lipid species in malaria infected patients using lipidomics profiling, to enhance diagnosis of malaria and to evaluate biochemical pathways activated during parasite infection.Methods: Using a multivariate characterization approach, 60 samples were representatively selected, 20 from each category (mild, severe and controls) of the 690 study participants between age of 0.5–6 years. Lipids from patient’s plasma were extracted with chloroform/methanol mixture and subjected to lipid profiling with application of the LCMS-QTOF method.Results: We observed a structured plasma lipid response among the malaria-infected patients as compared to healthy controls, demonstrated by higher levels of a majority of plasma lipids with the exception of even-chain length lysophosphatidylcholines and triglycerides with lower mass and higher saturation of the fatty acid chains. An inverse lipid profile relationship was observed when plasma lipids were correlated to parasitaemia.Conclusions: This study demonstrates how mapping the full physiological lipid response in plasma from malaria-infected individuals can be used to understand biochemical processes during infection. It also gives insights to how the levels of these molecules relate to acute immune responses.
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3.
  • Surowiec, Izabella, et al. (author)
  • Metabolic signature profiling as a diagnostic and prognostic tool in paediatric Plasmodium falciparum malaria
  • 2015
  • In: Open Forum Infectious Diseases. - : Oxford University Press. - 2328-8957. ; 2:2
  • Journal article (peer-reviewed)abstract
    • Background: Accuracy in malaria diagnosis and staging is vital in order to reduce mortality and post infectious sequelae. Herein we present a metabolomics approach to diagnostic staging of malaria infection, specifically Plasmodium falciparum infection in children. Methods: A group of 421 patients between six months and six years of age with mild and severe states of malaria with age-matched controls were included in the study, 107, 192 and 122 individuals respectively. A multivariate design was used as basis for representative selection of twenty patients in each category. Patient plasma was subjected to Gas Chromatography-Mass Spectrometry analysis and a full metabolite profile was produced from each patient. In addition, a proof-of-concept model was tested in a Plasmodium berghei in-vivo model where metabolic profiles were discernible over time of infection. Results: A two-component principal component analysis (PCA) revealed that the patients could be separated into disease categories according to metabolite profiles, independently of any clinical information. Furthermore, two sub-groups could be identified in the mild malaria cohort who we believe represent patients with divergent prognoses. Conclusion: Metabolite signature profiling could be used both for decision support in disease staging and prognostication.
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4.
  • Surowiec, Izabella, et al. (author)
  • The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children
  • 2017
  • In: Malaria Journal. - : BIOMED CENTRAL LTD. - 1475-2875. ; 16
  • Journal article (peer-reviewed)abstract
    • Background: Oxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initiation and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism.Methods: Detection of oxylipins and endocannabinoids from plasma samples from forty children with uncomplicated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatography mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA (R)) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis).Results: Forty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB2) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13-HODE, 9-HODE and 13-oxo-ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5-lipoxygenase (5-LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins in severe patients compared to uncomplicated ones. The endocannabinoids were extremely responsive to malaria infection with majority of this class of molecules found at higher levels in infected individuals compared to controls.Conclusions: It was possible to detect oxylipin and endocannabinoid molecules that can be potential biomarkers for differentiation between malaria infected individuals and controls and between different classes of malaria. Metabolic pathways that could be targeted towards an adjunctive therapy in the treatment of malaria were also pinpointed.
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5.
  • Akkineni, Susrut, et al. (author)
  • Amyloid-like amelogenin nanoribbons template mineralization via a low-energy interface of ion binding sites
  • 2022
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:19
  • Journal article (peer-reviewed)abstract
    • Protein scaffolds direct the organization of amorphous precursors that transform into mineralized tissues, but the templating mechanism remains elusive. Motivated by models for the biomineralization of tooth enamel, wherein amyloid-like amelogenin nanoribbons guide the mineralization of apatite filaments, we investigated the impact of nanoribbon structure, sequence, and chemistry on amorphous calcium phosphate (ACP) nucleation. Using full-length human amelogenin and peptide analogs with an amyloid-like domain, films of β-sheet nanoribbons were self-assembled on graphite and characterized by in situ atomic force microscopy and molecular dynamics simulations. All sequences substantially reduce nucleation barriers for ACP by creating low-energy interfaces, while phosphoserines along the length of the nanoribbons dramatically enhance kinetic factors associated with ion binding. Furthermore, the distribution of negatively charged residues along the nanoribbons presents a potential match to the Ca–Ca distances of the multi-ion complexes that constitute ACP. These findings show that amyloid-like amelogenin nanoribbons provide potent scaffolds for ACP mineralization by presenting energetically and stereochemically favorable templates of calcium phosphate ion binding and suggest enhanced surface wetting toward calcium phosphates in general.
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6.
  • Arjomandi Rad, Mohammad, 1987, et al. (author)
  • Datasets in design research: needs and challenges and the role of AI and GPT in filling the gaps
  • 2024
  • In: Proceedings of the Design Society. - 2732-527X. ; 4, s. 1919-1928
  • Conference paper (peer-reviewed)abstract
    • Despite the recognized importance of datasets in data-driven design approaches, their extensive study remains limited. We review the current landscape of design datasets and highlight the ongoing need for larger and more comprehensive datasets. Three categories of challenges in dataset development are identified. Analyses show critical dataset gaps in design process where future studies can be directed. Synthetic and end-to-end datasets are suggested as two less explored avenues. The recent application of Generative Pretrained Transformers (GPT) shows their potential in addressing these needs.
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7.
  • Bai, Yushi, et al. (author)
  • Protein nanoribbons template enamel mineralization
  • 2020
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 117:32, s. 19201-19208
  • Journal article (peer-reviewed)abstract
    • As the hardest tissue formed by vertebrates, enamel represents nature's engineering masterpiece with complex organizations of fibrous apatite crystals at the nanometer scale. Supramolecular assemblies of enamel matrix proteins (EMPs) play a key role as the structural scaffolds for regulating mineral morphology during enamel development. However, to achieve maximum tissue hardness, most organic content in enamel is digested and removed at the maturation stage, and thus knowledge of a structural protein template that could guide enamel mineralization is limited at this date. Herein, by examining a gene-modified mouse that lacked enzymatic degradation of EMPs, we demonstrate the presence of protein nanoribbons as the structural scaffolds in developing enamel matrix. Using in vitro mineralization assays we showed that both recombinant and enamel-tissue-based amelogenin nanoribbons are capable of guiding fibrous apatite nanocrystal formation. In accordance with our understanding of the natural process of enamel formation, templated crystal growth was achieved by interaction of amelogenin scaffolds with acidic macromolecules that facilitate the formation of an amorphous calcium phosphate precursor which gradually transforms into oriented apatite fibers along the protein nanoribbons. Furthermore, this study elucidated that matrix metalloproteinase-20 is a critical regulator of the enamel mineralization as only a recombinant analog of a MMP20-cleavage product of amelogenin was capable of guiding apatite mineralization. This study highlights that supramolecular assembly of the scaffold protein, its enzymatic processing, and its ability to interact with acidic carrier proteins are critical steps for proper enamel development.
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  • Bonde, Ingrid, et al. (author)
  • 2019: Report of the Swedish Climate Policy Council
  • 2019
  • Reports (other academic/artistic)abstract
    • Sweden’s overarching climate target is to reach net-zero emissions of greenhouse gases by 2045, followed by negative emissions. This long-term target is complemented by several interim targets. Those climate targets, the planning and monitoring system regulated under the Swedish Climate Act (2017:720), and the Swedish Climate Policy Council together form Sweden’s climate policy framework.The Climate Act took effect on 1 January 2018 after being adopted by a broad majority of the Riksdag (the Swedish Parliament). The mission of the Swedish Climate Policy Council is to determine if the government’s overall design of policies is compatible with the climate targets adopted by the Parliament and the Government. The Council uses a broad approach to evaluate the comprehensive policy, aiming to assess the effect of different policies on greenhouse gas emission trends. From this broad perspective, we examine the comprehensive policy in two dimensions: leadership and governance, and policy instruments.We define leadership and governance as policy targets, organisation and work procedures. Policy instruments include all the decisions and actions that directly affect citizens, companies and other stakeholders, including taxes, fees, regulations, public-sector consumption and investments.Since 1990, Sweden’s greenhouse gas emissions have decreased by 26%. This reduction mainly took place between 2003 and 2014. Thereafter the rate of reduction slowed, and 2017 was the third consecutive year in which emissions decreased by less than 1%. This rate is far too slow to achieve the climate targets, except for the upcoming 2020 target. The rate of reduction would need to accelerate to between 5% and 8% each year to meet future targets.The Swedish Climate Act states that within the framework of the budget bill, each year the Government must report climate policy decisions and actions taken during the previous year. The first climate assessment was presented to the Parliament together with the 2019 Budget Bill. It lacks assessments of how the reported climate policy decisions and actions might affect emissions. The Government recognised that additional actions are needed in several sectors, but did not state when and how decisions on these actions will be taken. The transitional government at the time said this was due to its limited mandate. This raises the stakes for the four-year Climate Action Plan that the Climate Act requires the Government to present in 2019.To achieve the long-term target, Sweden must reach the interim targets for 2030 and 2040, which include emissions that are not a part of the EU’s Emissions Trading System (EU ETS). All sectors matter, but reaching the 2030 goal depends heavily on progress in the transport sector, because domestic transport accounts for half of Sweden’s current emissions. In light of this, the Climate Policy Council has chosen to more closely examine policies that affect domestic transport emissions in a thematic section in this year’s report.The sectors included in the EU ETS – large-scale industry, civil aviation and power generation – account for almost 40% of Sweden’s greenhouse gas emissions. These sectors are included in the overarching target of net-zero emissions but not in the national interim targets, since the trading system is regulated at the EU level. There is currently no mechanism in place at the EU level to bring emissions covered by the trading system to net-zero in all Member States. Progress on these emissions is not in line with what is required for Sweden to reach its target of net-zero emissions.The report presents ten recommendations to the Swedish government: four general and six for transport policy.
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10.
  • Bonde, Ingrid, et al. (author)
  • 2020: Report of the Swedish Climate Policy Council
  • 2020
  • Reports (other academic/artistic)abstract
    • This report is the Climate Policy Council’s annual assessment of the Government’s overall work to achieve Sweden’s climate targets. It includes an update of developments in Sweden over the past year and an assessment of the Government’s Climate policy action plan, as required of the Council under our terms of reference.The Climate Policy Council would like to express its sincere thanks to the more than 100 organisations, researchers, experts and practitioners who contributed to this report. The conclusionsand recommendations presented here are the Climate Policy Council’s own.
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11.
  • Bonde, Ingrid, et al. (author)
  • Det klimatpolitiska ramverket : rapport 2018
  • 2018
  • Reports (other academic/artistic)abstract
    • Klimatpolitiska rådet bildades den 1 januari 2018 med uppgift att utvärdera hur regeringens samlade politik är förenlig med de klimatmål som riksdagen och regeringen har beslutat. Detta är rådets första rapport. Här presenteras rådets ledamöter och vårt uppdrag, som en del av Sveriges klimatpolitiska ramverk och dess internationella sammanhang i EU och FN.I Paris i december 2015 enades världens länder om ett nytt globalt klimatavtal under klimatkonventionen. Parisavtalet är historiskt då det är det första klimatavtalet som nästan alla världens länder står bakom. Processen bakom avtalet involverade också en lång rad andra viktiga aktörer inom näringsliv, forskning, civilsamhälle, städer och regioner.Efter Parisavtalet har ramverken för att hantera klimatproblemet förstärkts även på europeisk och nationell nivå. I juni 2017 beslutade riksdagen om ett klimatpolitiskt ramverk för Sverige med stöd av en mycket bred majoritet av riksdagens partier. Ramverket innehåller tre delar: långsiktiga mål, ett planerings- och uppföljningssystem samt ett klimatpolitiskt råd. Delar av ramverket är reglerat i en klimatlag.Det övergripande målet i det klimatpolitiska ramverket är att Sverige senast år 2045 inte har några nettoutsläpp av växthusgaser till atmosfären, för att därefter uppnå negativa utsläpp. Ramverket innehåller även etappmål på vägen mot det långsiktiga målet.Som en del av den parlamentariska överenskommelsen och det klimatpolitiska ramverket har regeringen inrättat det Klimatpolitiska rådet. Rådets huvuduppdrag är att ”utvärdera hur regeringens samlade politik är förenlig med de klimatmål som riksdag och regering har beslutat”.Uppdraget att granska regeringens samlade politik understryker klimatfrågans breda och tvärsektoriella karaktär. Att nå målen om ett fossilfritt samhälle utan några nettoutsläpp av växthusgaser inom 25 år innebär en omfattande samhällsförändring i ett komplext samspel mellan mängder av olika faktorer, aktörer och drivkrafter. Klimatfrågan spänner därmed också över i princip samtliga vetenskapliga fält. Det klimatpolitiska rådet består av personer med bred tvär- och mångvetenskaplig kompetens inom naturvetenskap, samhällsvetenskap, humaniora och teknikvetenskap. Till sitt förfogande har rådet ett kansli med tre heltidsanställda.Under första halvan av 2018 kommer rådet att forma inriktning och planer för arbetet. Klimatpolitiska rådet kommer att koncentrera sitt arbete till hur Sverige ska nå klimatmålen genom utsläppsminskningar och kompletterande åtgärder. Klimatanpassningsfrågor ingår inte i rådets arbetsområde.Sverige är inte det första landet som instiftar ett klimatpolitiskt råd. I bland annat Storbritannien, Danmark och Finland finns sedan flera år tillbaka liknande organ. I Sverige bidrar redan många andra myndigheter och organisationer på olika sätt med analys och kunskapsunderlag kring klimatpolitiken. Klimatpolitiska rådet har en unik roll bland myndigheter genom sitt fokus på den samhälleliga klimatomställningen, sitt oberoende och sitt breda mandat att utvärdera regeringens samlade politik.
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  • Bonde, Ingrid, et al. (author)
  • DN Debatt. ”Regeringens krispolitik måste rymmas i klimatramverket”
  • 2020
  • In: Dagens Nyheter. - : Bonnier. - 1101-2447.
  • Journal article (pop. science, debate, etc.)abstract
    • Klimatpolitiska rådet: Vi kommer att granska om återhämtningspolitiken är förenlig med Sveriges klimatmål.Idén med det av riksdagen beslutade klimatpolitiska ramverket är att klimatomställningen inte ska vara beroende av den ekonomiska eller politiska konjunkturen. 
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14.
  • Bonde, Ingrid, et al. (author)
  • Klimatpolitiska rådets rapport 2019
  • 2019
  • Reports (other academic/artistic)abstract
    • Klimatpolitiska rådet bildades den 1 januari 2018 som en del av Sveriges klimatpolitiska ramverk. Ramverket antogs året innan av en mycket bred majoritet i riksdagen.Rådets uppdrag är att utvärdera hur regeringens samlade politik är förenlig med de klimatmål som riksdagen och regeringen har beslutat. Arbetet ska redovisas i en årlig rapport. Denna första granskningsrapport är en genomlysning av den samlade politikens utformning i förhållande till klimatmålen. Den innehåller också våra kommentarer till regeringens första klimatredovisning i 2019 års budgetproposition. Utifrån detta presenterar vi ett antal övergripande observationer och rekommen-dationer. Därutöver har rådet i denna rapport valt att ytterligare fördjupa utvärderingen av politikens påverkan på klimatmålet för inrikes transporter.Klimatpolitiska rådet har fått ett brett och komplext uppdrag. Det finns inga beprövade metoder för att utvärdera hela regeringens politik mot ett långsiktigt mål. Det första årets arbete har delvis handlat om att utveckla arbetssätt och metoder samt att skapa dialog med andra myndigheter och aktörer. Vår ambition är att presentera en rapport som är vetenskapligt grundad och praktiskt användbar för regeringen och riksda-gen. Utifrån det första årets erfarenheter kommer sedan rådets arbete och rapporter att fortsätta utvecklas. Vi vill framföra vårt tack till alla de organisationer, forskare, experter och praktiker som har bidragit till den här rapporten genom att skicka in skriftliga underlag samt delta i seminarier och dialoger skriftliga underlag, seminarier och dialoger. Utöver att ge rekommendationer till regering och riksdag hoppas vi att rapporten ska bidra till en framåtsyftande diskussion mellan alla de aktörer som berörs av Sveriges klimatmål och som behövs för att de ska uppnås.
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15.
  • Bonde, Ingrid, et al. (author)
  • Klimatpolitiska rådets rapport 2020
  • 2020
  • Reports (other academic/artistic)abstract
    • Denna rapport är Klimatpolitiska rådets årliga utvärdering av regeringens samlade politik i förhållande till Sveriges klimatmål. Den innehåller en uppdatering av läget i Sverige under det senaste året och den bedömning av klimatpolitiska handlingsplan som rådet ska lämna enligt instruktion i det Klimatpolitiska ramverket.
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  • Bonde, Torben A., et al. (author)
  • Microbial biomass as a fraction of potentially mineralizable nitrogen in soils from long-term field experiments
  • 1988
  • In: Soil Biology and Biochemistry. - : Elsevier. - 0038-0717 .- 1879-3428. ; 20:4, s. 447-452
  • Journal article (peer-reviewed)abstract
    • Aerobic long-term incubations (40-wk) were employed to measure the potentially mineralizable nitrogen (N0) in five 30-yr old cropping systems. The cropping systems consisted of: (1) bare fallow; (2) cropping with no additions; (3) cropping with 80 kg N ha-1 y-1 as Ca(NO3)2; (4) cropping with 80 kg N ha-1 yr-1 as Ca(NO3)2 plus 1800kg C ha-1 yr-1 as straw; and (5) cropping with 80 kg N ha-1 yr-1 plus 1800 kg C ha-1 yr-1 as farmyard manure. The amounts of N mineralized during the 40-wk incubations were between 93 and 168 μg g-1 (302-543 kg N ha-1 down to 25cm depth) with the lowest value for the fallow and the highest for the farmyard manure treatment. Microbial biomass-C and -N were measured on four occasions during the incubations. The biomass-C showed a rapid decrease to week 4 (to 36% of the initial mass), a slower decrease to week 9 (to 23% of initial mass) and a very slow decline to the final determination at the end of the incubation (to 8% of initial mass). The biomass-N displayed a similar pattern. Two related models were employed to describe the kinetics of N-mineralization during incubation: (1) a two-component first-order; and (2) a simplified special case of the two-component model. In all cases except the straw-amended soil, the simplified two-component model offered the best description of the curves of accumulated mineral-N. The available fraction, Na, of soil organic-N had mineralization rate constants similar to those for mineralization of microbial biomass.
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20.
  • Brokken, Leon, et al. (author)
  • Interactions between polymorphisms in the aryl hydrocarbon receptor signalling pathway and exposure to persistent organochlorine pollutants affect human semen quality.
  • 2014
  • In: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 49:Jul 30, s. 65-73
  • Journal article (peer-reviewed)abstract
    • Persistent organic pollutants (POPs) may affect male reproductive function. Many dioxin-like POPs exert their effects by activation of the aryl hydrocarbon receptor (AHR) signalling pathway. We analysed whether gene-environment interactions between polymorphisms in AHR (R554K) and AHR repressor (AHRR P185A) and serum levels of markers of POP exposure 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (p,p'-DDE) and 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) are associated with 21 parameters of male reproductive function in 581 proven-fertile European and Greenlandic men. In Greenlandic men, AHR variants significantly modified the association between serum levels of both p,p'-DDE and CB-153 and inhibin B levels, sperm chromatin integrity, and seminal zinc levels. In the total cohort, interactions between AHRR variants and serum levels of CB-153 were associated with sperm chromatin integrity and the expression of the pro-apoptotic marker protein Fas. The data indicate that susceptibility to adverse effects of POP exposure on male reproductive function is dependent on polymorphisms in genes involved in AHR signalling.
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21.
  • Butler, Samuel J., et al. (author)
  • Functionalization of Recombinant Amelogenin Nanospheres Allows Their Binding to Cellulose Materials
  • 2016
  • In: Biotechnology Journal. - : Wiley. - 1860-6768. ; 11:10, s. 1343-1351
  • Journal article (peer-reviewed)abstract
    • Protein engineering to functionalize the self-assembling enamel matrix protein amelogenin with a cellulose binding domain (CBD) is used. The purpose is to examine the binding of the engineered protein, rh174CBD, to cellulose materials, and the possibility to immobilize self-assembled amelogenin nanospheres on cellulose. rh174CBD assembled to nanospheres ≈35 nm in hydrodynamic diameter, very similar in size to wild type amelogenin (rh174). Uniform particles are formed at pH 10 for both rh174 and rh174CBD, but only rh174CBD nanospheres showes significant binding to cellulose (Avicel). Cellulose binding of rh174CBD is promoted when the protein is self-assembled to nanospheres, compared to being in a monomeric form, suggesting a synergistic effect of the multiple CBDs on the nanospheres. The amount of bound rh174CBD nanospheres reached ≈15 mg/g Avicel, which corresponds to 4.2 to 6.3 × 10−7 mole/m2. By mixing rh174 and rh174CBD, and then inducing self-assembly, composite nanospheres with a high degree of cellulose binding can be formed, despite a lower proportion of rh174CBD. This demonstrates that amelogenin variants like rh174 can be incorporated into the nanospheres, and still retain most of the binding to cellulose. Engineered amelogenin nanoparticles can thus be utilized to construct a range of new cellulose based hybrid materials, e.g. for wound treatment.
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  • Carneiro, Karina M M, et al. (author)
  • Amyloid-like ribbons of amelogenins in enamel mineralization
  • 2016
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • Journal article (peer-reviewed)abstract
    • Enamel, the outermost layer of teeth, is an acellular mineralized tissue that cannot regenerate; the mature tissue is composed of high aspect ratio apatite nanocrystals organized into rods and inter-rod regions. Amelogenin constitutes 90% of the protein matrix in developing enamel and plays a central role in guiding the hierarchical organization of apatite crystals observed in mature enamel. To date, a convincing link between amelogenin supramolecular structures and mature enamel has yet to be described, in part because the protein matrix is degraded during tissue maturation. Here we show compelling evidence that amelogenin self-assembles into an amyloid-like structure in vitro and in vivo. We show that enamel matrices stain positive for amyloids and we identify a specific region within amelogenin that self-assembles into β-sheets. We propose that amelogenin nanoribbons template the growth of apatite mineral in human enamel. This is a paradigm shift from the current model of enamel development.
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23.
  • Danesi, Alexander L., et al. (author)
  • Uniaxial hydroxyapatite growth on a self‐assembled protein scaffold
  • 2021
  • In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:22
  • Journal article (peer-reviewed)abstract
    • Biomineralization is a crucial process whereby organisms produce mineralized tissues such as teeth for mastication, bones for support, and shells for protection. Mineralized tissues are composed of hierarchically organized hydroxyapatite crystals, with a limited capacity to regenerate when demineralized or damaged past a critical size. Thus, the development of protein‐based materials that act as artificial scaffolds to guide hydroxyapatite growth is an attractive goal both for the design of ordered nanomaterials and for tissue regeneration. In particular, amelogenin, which is the main protein that scaffolds the hierarchical organization of hydroxyapatite crystals in enamel, ame-logenin recombinamers, and amelogenin‐derived peptide scaffolds have all been investigated for in vitro mineral growth. Here, we describe uniaxial hydroxyapatite growth on a nanoengineered amelogenin scaffold in combination with amelotin, a mineral promoting protein present during enamel formation. This bio‐inspired approach for hydroxyapatite growth may inform the molecular mechanism of hydroxyapatite formation in vitro as well as possible mechanisms at play during mineralized tissue formation.
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  • Engelberth, Sarah A, et al. (author)
  • Progression of Self-Assembly of Amelogenin Protein Supramolecular Structures in Simulated Enamel Fluid
  • 2018
  • In: Biomacromolecules. - : American Chemical Society (ACS). - 1526-4602 .- 1525-7797. ; 19:10, s. 3917-3924
  • Journal article (peer-reviewed)abstract
    • Mechanisms of protein-guided mineralization in enamel, leading to organized fibrillar apatite nanocrystals, remain elusive. In vitro studies reveal recombinant human amelogenin (rH174), a matrix protein templating this process, self-assembles into a variety of structures. This study endeavors to clarify the self-assembly of rH174 in physiologically relevant conditions. Self-assembly in simulated enamel fluid was monitored up to 2 months. At alkali (7.3-8.7) and acidic (5.5-6.1) pH ranges, a distinct progression in formation was observed from nanospheres (17-23 nm) to intermediate-length nanorods, concluding with the formation of long 17-18 nm wide nanoribbons decorated with nanospheres. Assembly in acidic condition progressed quicker to nanoribbons with fewer persistent nanospheres. X-ray diffraction exhibited reflections characteristic of antiparallel β-sheets (4.7 and 9.65 Å), supporting the model of amyloid-like nanoribbon formation. This is the first observation of rH174 nanoribbons at alkaline pH as well as concurrent nanosphere formation, indicating both supramolecular structures are stable together under physiological conditions.
  •  
26.
  • Jiang, Lingdong, et al. (author)
  • Temperature and pH Controlled Self-Assembly of a Protein-Polymer Biohybrid
  • 2018
  • In: Macromolecular Chemistry and Physics. - : Wiley. - 1022-1352. ; 219:7
  • Journal article (peer-reviewed)abstract
    • A novel pH and temperature dual-responsive bioconjugate is prepared by grafting thermoresponsive polymer chains from a pH-responsive protein amelogenin via atom transfer radical polymerization. To the best of our knowledge, this is the first time that amelogenin is exploited to prepare a hybrid biomaterial with new stimuli-responsive property. In both basic and acidic solutions the protein-polymer bioconjugate is able to self-assemble into uniform and stable nanoparticles when heated to above the lower critical solution temperature of the polymer. The amelogenin-based stimuli-responsive bioconjugate may be of great use in the fields of bioseparation and drug/gene delivery, and the synthetic approach reported here should provide a convenient means to preparing amelogenin-based functional biohybrid materials.
  •  
27.
  • Lindberg, T., et al. (author)
  • Distribution of15N in the soil-plant system during a four-year field lysimeter study with barley (Hordeum distichum L.) and perennial meadow fescue (Festuca pratensis Huds.)
  • 1989
  • In: Plant and Soil. - Dordrecht, Netherlands : Kluwer Academic Publishers. - 0032-079X .- 1573-5036. ; 119:1, s. 25-37
  • Journal article (peer-reviewed)abstract
    • An annual cereal, barley, and a perennial grass ley, meadow fescue, were grown in field lysimeters in Sweden and fertilized with 12 and 20g Ca(NO3)2-N m-2 yr-1, respectively. Isotope-labeled (15N) fertilizer was added during year 1 of the study, whereafter similar amounts of unlabeled N were added during years 2 and 3. The grass ley lysimeters were ploughed after the growing season of year 3 and sown with barley during year 4. The barley harvest in year 1 removed 59% of the added fertilizer N, while the fertilizer N export by two meadow fescue harvests in year 1 was 65%. The labeled N export decreased rapidly after year 1, especially in the barley, but increased slightly after ploughing of the grass ley.The microbial biomass, measured with the chloroform fumigation method, incorporated a maximum of 1.4-1.7% of the labeled N during the first seven weeks after application. Later on, the incorporation stabilized at less than 1% in both cropping systems.The susceptibility of the residual labeled N to mineralization was evaluated three years after application by means of long-term laboratory incubations. The curves of cumulative mineralized N were described by a two-component first-order regression model that differentiated between an available and a more recalcitrant fraction of potentially mineralizable N. There was no difference in the amounts of potentially mineralizable N between the cropping systems. The labeled N comprised 5 and 2% of the amounts of potentially mineralizable N in the available and more recalcitrant fraction, respectively. The mineralization rate constants for the labeled N were almost twice as high as for the total potentially mineralizable N. The available fraction of the total potentially mineralizable N was 12%, while twice that proportion of the labeled N was available.It was concluded that the short-term ley did not differ from the annual crop with respect to the early disposition of the fertilizer N and the behaviour of the residual organic N.
  •  
28.
  • Martinsson Bonde, Julian, 1992, et al. (author)
  • Morpheus: The Development and Evaluation of a Software Tool for Morphological Matrices
  • 2022
  • In: Proceedings of NordDesign 2022: How Product and Manufacturing Design Enable Sustainable Companies and Societies.
  • Conference paper (peer-reviewed)abstract
    • The Morphological Matrix is a well-known and established method for synthesising concepts in engineering design. With the aim to improve its applicability, the method has been implemented into a software tool, which then has been introduced in engineering courses at Chalmers University of Technology. In this paper, the tool and its most important functions are presented and discussed, along with experiences from its use in design projects. It was demonstrated that the tool can ease the process of creating and modifying morphological matrices. Furthermore, the tool demonstrated the ability to generate and keep track of large quantities of solutions, which has previously been difficult as morphological matrices are typically hand drawn or created using an Excel sheet. However, less desired effects were encountered as the tool was perceived by some students as more of a screening and down-selection method, rather than as a tool for synthesising concepts. The learnings and the way forward in education and the industrial context are discussed.
  •  
29.
  • Martinsson Bonde, Julian, 1992, et al. (author)
  • The impact of specialized software on concept generation
  • 2024
  • In: Proceedings of the Design Society. - 2732-527X. ; 4, s. 663-672
  • Conference paper (peer-reviewed)abstract
    • Software implementations of traditional engineering design methods can potentially enrich the original methods. A study was conducted to better understand how concept generation can be facilitated using software. Participants of the study were asked to generate concepts using either specialized software, or by using traditional means, for applying function-means modeling and morphological matrices. A concept concretization metric was used to evaluate the results, which indicated that there are both positive and negative aspects of performing concept generation using specialized software.
  •  
30.
  • Robertson, Kerstin, et al. (author)
  • Microbial biomass in relation to C and N mineralization during laboratory incubations
  • 1988
  • In: Soil Biology and Biochemistry. - : Elsevier. - 0038-0717 .- 1879-3428. ; 20:3, s. 281-286
  • Journal article (peer-reviewed)abstract
    • Net carbon and nitrogen mineralization rates were determined for an arable soil during 12 weeks at 37†C using an aerobic incubation-leaching technique. The amounts of mineralized C and N were compared to changes in the contents of C and N in microbial biomass (as determined by the chloroform fumigation incubation method; CFIM) during the incubation and to amounts of organic C and N in the leachates. Microorganisms were also followed by direct counting of bacteria, measurements of total hyphal lengths and fluorescein diacetate (FDA)-active hyphae, and by most probable number determinations of protozoa (naked amoebae and flagellates).Numbers of naked amoebae increased nearly 10-fold initially and then decreased between weeks 6 and 12. Bacterial numbers and FDA-active hyphae decreased during the incubation, and the relative composition changed slightly in favour of bacteria. Total hyphal lengths remained almost constant.A total of 105 μg N g'- soil dry wt and 1179 μg C g- soil dry wt was mineralized during the incubation, while the microbial N pool decreased by 42 γm- soil dry wt and the microbial C pool decreased by 225μ g- soil dry wt. Soluble organic matter in the leachates amounted to 16 and 31% of mineralized C and N, respectively.The possibility of measuring C mineralization with less frequent teachings and determinations of N mineralization offers an easy method for assessing changes in labile soil organic matter over time or for comparisons between soils. Through the use of appropriate C-to-N ratios, the N-content in the labile pool can be calculated.
  •  
31.
  • Shen, Xiantao, et al. (author)
  • Bacterial Imprinting at Pickering Emulsion Interfaces.
  • 2014
  • In: Angewandte Chemie (International edition). - : Wiley. - 1521-3773. ; 53:40, s. 10687-10690
  • Journal article (peer-reviewed)abstract
    • The tendency of bacteria to assemble at oil-water interfaces can be utilized to create microbial recognition sites on the surface of polymer beads. In this work, two different groups of bacteria were first treated with acryloyl-functionalized chitosan and then used to stabilize an oil-in-water emulsion composed of cross-linking monomers that were dispersed in aqueous buffer. Polymerization of the oil phase followed by removal of the bacterial template resulted in well-defined polymer beads bearing bacterial imprints. Chemical passivation of chitosan and cell displacement assays indicate that the bacterial recognition on the polymer beads was dependent on the nature of the pre-polymer and the target bacteria. The functional materials for microbial recognition show great potential for constructing cell-cell communication networks, biosensors, and new platforms for testing antibiotic drugs.
  •  
32.
  • Svensson Bonde, Johan, et al. (author)
  • Histidine tag fusion increases expression levels of active recombinant amelogenin in Escherichia coli
  • 2006
  • In: Protein Expression and Purification. - : Elsevier BV. - 1046-5928. ; 48:1, s. 134-141
  • Journal article (peer-reviewed)abstract
    • Amelogenin is a dental enamel matrix protein involved in formation of dental enamel. In this study, we have expressed two different recombinant murine amelogenins in Escherichia coli: the untagged rM179, and the histidine tagged rp(H)M180, identical to rM179 except that it carries the additional N-terminal sequence MRGSHHHHHHGS. The effects of the histidine tag on expression levels, and on growth properties of the amelogenin expressing cells were studied. Purification of a crude protein extract containing rp(H)M 180 was also carried out using IMAC and reverse-phase HPLC. The results of this study showed clearly that both growth properties and amelogenin expression levels were improved for E coli cells expressing the histidine tagged amelogenin rp(H)M 180, compared to cells expressing the untagged amelogenin rM179. The positive effect of the histidine tag on amelogenin expression is proposed to be due to the hydrophilic nature of the histidine tag, generating a more hydrophilic amelogenin, which is more compatible with the host cell. Human osteoblasts treated with the purified rp(H)M 180 showed increased levels of secreted osteocalcin, compared to untreated cells. This response was similar to cells treated with enamel matrix derivate, mainly composed by amelogenin, suggesting that the recombinant protein is biologically active. Thus, the histidine tag favors expression and purification of biologically active recombinant amelogenin. (c) 2006 Elsevier Inc. All rights reserved.
  •  
33.
  • Svensson Bonde, Johan, et al. (author)
  • In vitro preparation of amelogenin nanoparticles carrying nucleic acids.
  • 2014
  • In: Biotechnology Letters. - : Springer Science and Business Media LLC. - 1573-6776 .- 0141-5492. ; 36:6, s. 1349-1357
  • Journal article (peer-reviewed)abstract
    • Amelogenin, a matrix protein involved in biomineralization of enamel, can self-assemble to form nanospheres in a pH-dependent manner. Nucleic acids (single-stranded, double-stranded, and plasmid DNA, as well as RNA) could be co-precipitated with amelogenin, demonstrating a strong binding of nucleic acids to amelogenin. The amounts of co-precipitated nucleic acids were analyzed and binding levels upto 90 μg DNA/mg amelogenin was achieved. The co-precipitation could also be carried out in a bacterial cell homogenate, and no bacterial proteins were found in the amelogenin aggregates, suggesting specificity for nucleic acid binding. Dynamic light scattering showed that amelogenin nanosphere structure is maintained upon DNA binding with an upto 2.6 nm increase in diameter. The reported binding of nucleic acids to amelogenin can be explored practically for nucleic acid separation.
  •  
34.
  • Svensson Bonde, Johan, et al. (author)
  • One-step purification of recombinant human amelogenin and use of amelogenin as a fusion partner.
  • 2012
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3
  • Journal article (peer-reviewed)abstract
    • Amelogenin is an extracellular protein first identified as a matrix component important for formation of dental enamel during tooth development. Lately, amelogenin has also been found to have positive effects on clinical important areas, such as treatment of periodontal defects, wound healing, and bone regeneration. Here we present a simple method for purification of recombinant human amelogenin expressed in Escherichia coli, based on the solubility properties of amelogenin. The method combines cell lysis with recovery/purification of the protein and generates a >95% pure amelogenin in one step using intact harvested cells as starting material. By using amelogenin as a fusion partner we could further demonstrate that the same method also be can explored to purify other target proteins/peptides in an effective manner. For instance, a fusion between the clinically used protein PTH (parathyroid hormone) and amelogenin was successfully expressed and purified, and the amelogenin part could be removed from PTH by using a site-specific protease.
  •  
35.
  • Svensson Bonde, Johan, et al. (author)
  • Random mutagenesis of amelogenin for engineering protein nanoparticles.
  • 2015
  • In: Biotechnology and Bioengineering. - : Wiley. - 1097-0290 .- 0006-3592. ; 112:7, s. 1319-1326
  • Journal article (peer-reviewed)abstract
    • Nanoparticles made from recombinant proteins offer excellent potential for several nanotechnological applications. However, only a very limited number of proteins are currently being used for such purposes due to limited availability and stability. Therefore, we have investigated the enamel matrix protein amelogenin as a new alternative protein for use as recombinant nanoparticles. Amelogenin is a robust protein that has the ability to self-assemble into nanosized particles termed nanospheres. This self-assembly property of amelogenin is highly pH-dependent, and modifications of the solubility behavior for amelogenin can be particularly important for some applications such as drug delivery, where responsiveness at a specific pH is an essential property. In this study, an amelogenin mutant library was created and used to screen amelogenin variants with modified solubility/aggregation profiles in response to externally applied pH changes. Fifty amelogenin mutants were identified and produced recombinantly, purified and characterized. Several mutants with distinct solubility profiles were obtained that could form uniform nanospheres, ranging from 30 to 60 nm in hydrodynamic diameter. The mutants displayed a shifted onset of pH-dependent aggregation compared to wild-type amelogenin. At physiological pH, some mutants formed soluble nanospheres, while others generated nanosphere aggregates, suggesting different practical uses for the different mutants. By mixing and co-assembling mutant and wild-type amelogenin at different ratios, the level of nanosphere aggregation could be tuned at a given pH. By exploring combinations of different amelogenin variants it is possible to control aggregation events in nanomedical applications where a specific pH response is required. Biotechnol. Bioeng. 2015;9999: 1-8. © 2014 Wiley Periodicals, Inc.
  •  
36.
  • Svensson Bonde, Johan (author)
  • Recombinant amelogenin - Strategies for purification and protein processing
  • 2008
  • Doctoral thesis (other academic/artistic)abstract
    • Amelogenin is an extracellular matrix protein involved in formation of enamel during early tooth development. By interacting with the forming enamel crystallites amelogenin affects their growth, so that highly elongated hydroxyapatite crystals are formed. Early during the enamel formation amelogenin is proteolytically processed, which is essential for correct enamel formation. However, the exact mechanism of amelogenin in enamel formation is not fully understood. Amelogenin has also been found to have signal molecule-like properties, which suggests that amelogenin has other functions during tooth development. Expression of amelogenin has also been discovered in non-dental tissues, indicating of an even wider function of the protein. An extract from porcine enamel matrix, mainly composed of amelogenin, has been found to have regenerative properties on dental tissues and to improve wound healing, which makes amelogenin interesting from a therapeutic point of view. Amelogenin can also be used to modulate hydroxyapatite formation in vitro, in order to create new improved materials. An increased demand of amelogenin is probable, and especially recombinant amelogenin is of interest since it does not suffer from some of the drawbacks of amelogenin from animal sources, such as risk of viral contamination. This doctoral dissertation presents results from three studies. The main objective with the work has been to improve production of recombinant amelogenin. In the first study it was shown that the expression levels of recombinant murine amelogenin in Escherichia coli are enhanced when an N-terminal histidine tag is fused to the protein. This also leads to an improvement of the growth properties of the host cells, which grow to higher cell densities. The histidine tagged amelogenin can be purified using immobilized metal ion affinity chromatography (IMAC). In the second study a new method for purification of recombinant human amelogenin is described. By heat treating amelogenin expressing E. coli cells at low pH the cells can be disrupted, which releases soluble amelogenin into the surrounding solution. The host cell proteins denatures by the same treatment and form a precipitate. By separating the soluble fraction from the precipitate and cell debris a more than 95 % pure amelogenin solution is obtained. The method combines cell lysis with separation of amelogenin from the host cell proteins, and significantly improves the yield compared to previously used methods. In the third study the proteolytic processing of human amelogenin by matrix metalloproteinase-20 (MMP-20) was examined. Cleavage of amelogenin generates a mixture of different amelogenin polypeptides, similar to what is found in the enamel matrix. The identified MMP-20 cleavage sites on human amelogenin were located in the C- and N-terminus, similar to what has been previously reported for porcine and murine amelogenin. We found that MMP-20 can be permanently inactivated by heat treatment at low pH. This makes it possible to generate amelogenin preparations, proteolytically degraded to different degrees, by terminating the cleavage reaction at a certain point. The results presented in this doctoral dissertation provide improvements to the field that are useful for production of recombinant amelogenin and for future study of amelogenin function.
  •  
37.
  • Svensson Bonde, Johan, et al. (author)
  • Use of human amelogenin in molecular encapsulation for the design of pH responsive microparticles
  • 2012
  • In: BMC Biotechnology. - : Springer Science and Business Media LLC. - 1472-6750. ; 12
  • Journal article (peer-reviewed)abstract
    • Background: Proteins can be used in drug delivery systems to improve pharmacological properties of an active substance. Differences in pH between tissues can be utilized in order to achieve a targeted drug release at a specific location or tissue, such as a tumor. The enamel matrix protein amelogenin has a pH dependent solubility profile and self-assemble to form aggregates at neutral pH. This could make amelogenin useful in the design of pH responsive drug delivery systems. Results: In this study amelogenin was evaluated as a pH responsive component in drug delivery applications. This was achieved by testing the ability of amelogenin to entrap/release other proteins upon changes in pH, and by testing if amelogenin could confer pH responsiveness to an existing and versatile drug delivery system, such as gelatin microparticles. Amelogenin was able to encapsulate bovine serum albumin and insulin, which were used as model target proteins. The composite aggregates of amelogenin and target protein were formed at neutral pH and could be reversibly solubilized at weakly acidic pH. Gelatin microparticles prepared in the presence of amelogenin, showed a modulated structure in response to pH change, when studied by scanning electron microscopy, compared to particles without amelogenin. At neutral pH amelogenin induced formation of pores in the particle surface, which were not present at acidic pH, or in particles lacking amelogenin. Conclusions: The results from this study demonstrate that amelogenin can be a useful component in drug delivery systems in order to achieve a pH dependent response.
  •  
38.
  • Öster, Carl, et al. (author)
  • Characterization and assembly of a GFP-tagged cylindriform silk into hexameric complexes.
  • 2014
  • In: Biopolymers. - : Wiley. - 0006-3525. ; 101:4, s. 378-390
  • Journal article (peer-reviewed)abstract
    • Spider silk has been studied extensively for its attractive mechanical properties and potential applications in medicine and industry. The production of spider silk, however, has been lagging behind for lack of suitable systems. Our approach focuses on solving the production of spider silk by designing, expressing, purifying and characterizing the silk from cylindriform glands. We show that the cylindriform silk protein, in contrast to the commonly used dragline silk protein, is fully folded and stable in solution. With the help of GFP as a fusion tag we enhanced the expression of the silk protein in Escherichia coli and could optimize the downstream processing. Secondary structures analysis by circular dichroism and FTIR shows that the GFP-Silk fusion protein is predominantly α-helical, and that pH can trigger a α- to β-transition resulting in aggregation. Structural analysis by small angle x-ray scattering suggests that the GFP-Silk exists in the form of a hexamer in solution.
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