| 1. |
- Belgrano, Andrea, et al.
(författare)
-
Mapping and Evaluating Marine Protected Areas and Ecosystem Services: A Transdisciplinary Delphi Forecasting Process Framework
- 2021
-
Ingår i: Frontiers in Ecology and Evolution. - : Frontiers Media SA. - 2296-701X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Marine Protected Areas (MPAs) are an important tool for management and conservation and play an increasingly recognised role in societal and human well-being. However, the assessment of MPAs often lacks a simultaneous consideration of ecological and socio-economic outcomes, and this can lead to misconceptions on the effectiveness of MPAs. In this perspective, we present a transdisciplinary approach based on the Delphi method for mapping and evaluating Marine Protected Areas for their ability to protect biodiversity while providing Ecosystem Services (ES) and related human well-being benefits – i.e., the ecosystem outputs from which people benefit. We highlight the need to include the human dimensions of marine protection in such assessments, given that the effectiveness of MPAs over time is conditional on the social, cultural and institutional contexts in which MPAs evolve. Our approach supports Ecosystem-Based Management and highlights the importance of MPAs in achieving restoration, conservation, and sustainable development objectives in relation to EU Directives such as the Marine Strategy Framework Directive (MSFD), the Maritime Spatial Planning Directive (MSPD), and the Common Fisheries Policy (CFP).
|
|
| 2. |
- Bergström, Lena, et al.
(författare)
-
Ekologisk kompensation i kustmiljön : Hur kan man uppväga förluster av biologisk mångfald och ekosystemtjänster i samband med mänsklig verksamhet i kustområdet?
- 2021
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sveriges kustmiljöer är utsatta för olika typer av mänsklig påverkan, med negativa effekter på arter, livsmiljöer och ekosystemtjänster. Enligt skadelindringshierarkin ska negativa effekter från mänsklig verksamhet i första hand undvikas, minimeras eller avhjälpas. I de kvarstående fall där skada trots dessa åtgärder är oundviklig, kan ekologisk kompensation vara ett sätt att mildra effekterna i syfte att bibehålla eller öka biologisk mångfald och ekosystemtjänster.I projektet ECOCOA har vi undersökt om och hur ekologisk kompensation skulle kunna användas i förvaltningen av kustområden. Vår målsättning har varit att bidra till en vetenskapligt grundad syn på hur ekologisk kompensation skulle kunna medverka till att stoppa nettoförluster av biologisk mångfald och ekosystemtjänster. Eftersom kompensation kan beröra en mängd aktörer och sakägare med olika intressen och perspektiv är det viktigt med en transparent process som hanteras på ett jämförbart sätt mellan olika områden och fall. En viktig flaskhals idag är brist på praktisk erfarenhet hos aktörer om hur kompensationen ska kunna tillämpas. Vi har utvecklat ett ramverk utifrån de steg som man behöver beakta i en bedömning av skada och kompensationsbehov, med fokus på att öka förutsättningarna för en transparent bedömningsprocess. Det föreslagna ramverket bygger på fyra steg: 1) skadebedömning; 2) bedömning av kompensationsbehov; 3) val av kompensationsåtgärder; och 4) utvärdering av resultat. Ramverket baserar sig på att tydliggöra samband mellan ekosystemets strukturer och de nyttigheter dessa kan medföra för människan, där nyttigheter är beroende av ekosystemtjänster, ekosystemtjänster av funktioner, och funktioner av strukturer. Vi kopplar ramverket till en utvärdering av aktuellt kunskapsläge kring åtgärders effektivitet i kustområdet. Viktiga livsmiljöer som ingår är ålgräs, grunda vegetationsklädda mjukbottnar, naturligt vegetationsfria mjukbottnar, tångbälten, musselbankar, stenrev och kustnära våtmarker.Vi har med hjälp av ramverket utvärderat nuvarande och möjliga tillämpningar av ekologisk kompensation. Utvärderingen har gjorts dels genom ett fullständigt exempel som beskriver förlust av ålgräsängar och dels genom att undersöka befintliga fall och sammanhang där kompensation är eller skulle kunna bli relevant. Fallen bygger på i) domslut gällande tillståndspliktig vattenverksamhet, ii) dagens hantering av småskalig exploatering i kustområden, samt iii) tillämpningen av särskild fiskeavgift ur ett kompensationsperspektiv. Slutligen har vi utvecklat förslag på hur liknande tillämpningar skulle kunna se ut för ytterligare livsmiljöer i tillägg till ålgräs.Våra resultat visar det finns fortsatt stor osäkerhet kring hur kompensationsprocesser och kompensationsåtgärder fungerar i praktiken. Samtidigt är det en realitet att man idag i de allra flesta fall exploaterar utan kompensation, eller med otillräcklig kompensation. Detta innebär i praktiken att förluster värderas till noll, det vill säga att man accepterar förluster på biologisk mångfald, ekosystemtjänster och nyttigheter, och att de skador som uppstår inte uppmärksammas i form av åtgärdsbehov som ska täckas av den som orsakar skadan. Eftersom tillämpningen av vårt ramverk synliggör värdet av att förvalta biologisk mångfald och ekosystemtjänster tillsammans kan det även stödja förvaltningen av kustområden i enlighet med ekosystemansatsen på en mer generell nivå.Våra resultat synliggör vikten av att värna biologisk mångfald. Vår genomgång av potentiella kompensationsåtgärder, som redogörs för i rapporten, visar med tydlighet att det är kostsamt att först förstöra och sedan restaurera, i stället för att skydda och undvika skada i första hand. Vi ser dock ett utrymme och ett behov av att förbättra användningen av ekologisk kompensation som ett av många verktyg för att värna biologisk mångfald och ekosystemtjänster i svenska kustmiljöer i enlighet med miljöbalken. ECOCOAs ramverk tillsammans med kaskadmodeller för viktiga livsmiljöer och information om potentiella åtgärder, kunde här fungera som en gemensam utgångspunkt vid diskussioner, samrådsprocesser och bedömningar.
|
|
| 3. |
|
|
| 4. |
- Cole, Scott, et al.
(författare)
-
Environmental compensation for biodiversity and ecosystem services : A flexible framework that addresses human wellbeing
- 2021
-
Ingår i: Ecosystem Services. - : Elsevier BV. - 2212-0416 .- 2212-0416. ; 50
-
Tidskriftsartikel (refereegranskat)abstract
- Environmental compensation should address negative impacts from human activities on nature, including loss of biodiversity and ecosystem services. However, successful compensation, achieving no net loss, requires broad quantitative information on different types of losses and gains. We find that the scope of compensatory schemes varies in what is considered compensable, which makes it challenging to apply a conceptual approach consistently across schemes with different needs. We propose a flexible yet structured framework for determining which values should be compensated and how. Our framework focuses specifically on habitat deterioration and is illustrated with a case study involving loss of eelgrass habitat. The framework helps identify compensation needs and selects among suitable compensation options, merging science-based information with normative issues and local concerns. By integrating the ecosystem services cascade model, it encompasses aspects from biodiversity structure to human wellbeing. The framework prefers in-kind compensation because this targets the structure level and thus meets compensation needs in all subsequent levels of the cascade model; further, it is more likely to capture non-instrumental values (i.e. in nature) and reduce exposure to uncertainty. We highlight the importance of spatial aspects of ecosystem functions, services and their subsequent impacts on wellbeing. Although our selection hierarchy assumes a similar and nearby principle for habitat restoration (preference for in-kind/on-site), this criterion is not universal. We underscore the hierarchy's implicit normative assumptions and suggest that apparent disagreement about who should benefit may be traced to an unresolved conflict between egalitarianism and utilitarianism.
|
|
| 5. |
- Faithfull, Carolyn
(författare)
-
Ekosystemtjänstanalyser som stöd för en regional ekosystembaserad havsförvaltning : Erfarenheter från tre pilotområden: 8-fjordar, Stockholms skärgård och Södra Bottenhavet
- 2024
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Kartläggning och analys av ekosystemtjänster är viktiga verktyg för att synliggöra människans relation till och beroende av ekosystemet. De kan till exempel påvisa samband mellan processer i ekosystemet och samhället, och användas som underlag för att diskutera avvägningar mellan olika mål och intressen. I ekosystembaserad havsförvaltning kan diskussioner om ekosystemtjänster öka aktörers förståelse för ekosystemet som grund för vårt nyttjande av havet. De kan också stödja åtgärdsarbete och strategisk planering. Här presenterar vi analyser av ekosystemtjänster som tagits fram som underlag för en regional ekosystembaserad havsförvaltning i Södra Bottenhavet, Stockholms skärgård och området 8+fjordar i Bohuslän. Vi har dels använt två olika metoder för att kartlägga utbredningen av ekosystemtjänster och associerade nyttigheter i pilotområden - en naturbaserad metod som utgår från utbredningen av ekosystemkomponenter och en öppen GIS-metod för att samla in lokal kunskap om ekosystemtjänster från intressenter och allmänhet.Den naturbaserade kartläggningen gjordes för Södra Bottenhavet och Stockholms skärgård. Studien hade som mål att utveckla och testa en metod för att kartlägga kustnära ekosystemtjänster utifrån kartor av arter och livsmiljöer och utvärdera hur metoden kan användas för ekosystembaserad planering. Vi har gjort en bedömning av vilka ekosystemtjänster som är relevanta att kartlägga med metoden i dessa områden och vilka arter och livsmiljöer som främst kan förväntas bidra till dessa tjänster. För att lätt kunna dela resultaten har vi utvecklat en app som tillåter en användare att ta fram potentiella ekosystemtjänstkartor utifrån kartor över arter och livsmiljöer. Som nästa steg behöver appen utvärderas tillsammans med användare, för att testa användbarhet och vidare utvecklingsbehov.Öppen-GIS-analysen gjordes inom projektet 8+fjordar, där intressenter och allmänhet bjöds in till workshops för att beskriva sin syn på områdets värden och vad som påverkar miljön i området. De resulterande GIS-lagren ger en bild av hur användare av det lokala ekosystemet uppfattar sin närmiljö och vilka ekosystemtjänster de värdesätter och nyttjar. En initial utvärdering visar att resultaten kan användas till exempel för att identifiera platser där det finns konflikter mellan olika användningar av havet och peka ut behov av åtgärder för att lösa dessa konflikter. Processen att ta fram underlagen bidrog dessutom till ett gemensamt lärande inom projektet.Den tredje metoden som vi har använt är en enkät- och intervjustudie för att undersöka markägares attityder och preferenser i samband med åtgärdsarbete i Stockholms skärgård. Den här studien fokuserade på vilka ekosystemtjänster och nyttigheter markägare värdesätter i naturtypen grunda havsvikar. Resultatet kompletterar kunskapen om människans förhållande till denna naturtyp och lägger en viktig grund för att inkludera sociala mål och indikatorer i arbetet för att skydda och restaurera grunda havsvikar.Ekosystemtjänster är fortfarande ett abstrakt begrepp för många och rapporten syftar till att genom exempel synliggöra hur ekosystemtjänster kan användas för att stödja en långsiktigt hållbar förvaltning av kustområden. Att ta hänsyn till det komplexa samspelet mellan människa och natur är en central del av ekosystembaserad förvaltning. Våra tre exempel fyller delvis olika syften inom denna komplexitet. De kan användas individuellt för särskilda ändamål eller komplettera varandra. I samtliga fall är det viktigt att arbeta nära aktörer för att tydligt definiera behov, syften, och säkerställa att de slutliga resultaten blir lokalt användbara.
|
|
| 6. |
- Reuterswärd, Philippa, et al.
(författare)
-
Levels of human proteins in plasma as indicators for acute severe pediatric malaria
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundExisting low resource diagnostics for malaria infection suffer from sensitivity and specificity issues while lacking sufficient prognostic value. Identifying human host proteins could improve the possibilities to predict the risk of development of acute severe malaria. This will possible enable improved treatment and thereby lead to a decrease in mortality of malaria infected children. Furthermore, discovering host proteins with altered levels during active infection could generate leads to better understand host-parasite interaction.ResultsHere, we have analyzed a total of 541 pediatric plasma samples that were collected from community controls and individuals with mild or severe malaria in Rwanda. Protein profiles of these plasma samples were generated with an antibody-based suspension bead array containing 255 antibodies targeting 115 human proteins. We present 22 proteins with a strong discriminatory capacity (adjusted p-values below 10-19) for separating malaria cases from community controls. This panel of proteins contains among others acute phase proteins and proteins connected to cell adhesion and migration. Among these, three proteins showed lower plasma levels in the group of malaria-infected individuals compared to the control group. One of these proteins is the anti-adhesive secreted protein acidic and cysteine rich (SPARC) with possible connections to parasite cytoadhesion. A multi-protein panel of six proteins, including SPARC, could differentiate between controls and malaria cases with an AUC of 0.98. Furthermore, a panel of 37 proteins, including proteins associated to erythrocyte membranes, was identified as candidates for separation of mild and severe malaria patients (adjusted pvalues below 0.05).ConclusionThe herein identified set of human proteins has a significant discriminatory capacity between community controls and malaria cases. We also present proteins offering the possibility to enable stratification and risk prediction for the development of severe malaria. This constitutes an important set that could enable enhanced understanding and thereby also possibilities for better treatment of acute severe pediatric malaria.
|
|
| 7. |
- Reuterswärd, Philippa, et al.
(författare)
-
Levels of human proteins in plasma associated with acute paediatric malaria
- 2018
-
Ingår i: Malaria Journal. - : BMC. - 1475-2875. ; 17
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The intimate interaction between the pathophysiology of the human host and the biology of the Plasmodium falciparum parasite results in a wide spectrum of disease outcomes in malaria. Development of severe disease is associated with a progressively augmented imbalance in pro- and anti-inflammatory responses to high parasite loads and sequestration of parasitized erythrocytes. Although these phenomena collectively constitute common denominators for the wide variety of discrete severe malaria manifestations, the mechanistic rationales behind discrepancies in outcome are poorly understood. Exploration of the human pathophysiological response by variations in protein profiles in plasma presents an excellent opportunity to increase the understanding. This is ultimately required for better prediction, prevention and treatment of malaria, which is essential for ongoing elimination and eradication efforts. Results: An affinity proteomics approach was used to analyse 541 paediatric plasma samples collected from community controls and patients with mild or severe malaria in Rwanda. Protein profiles were generated with an antibody-based suspension bead array containing 255 antibodies targetting 115 human proteins. Here, 57 proteins were identified with significantly altered levels (adjusted p-values<0.001) in patients with malaria compared to controls. From these, the 27 most significant proteins (adjusted p-values<10(-14)) were selected for a stringent analysis approach. Here, 24 proteins showed elevated levels in malaria patients and included proteins involved in acute inflammatory response as well as cell adhesion. The remaining three proteins, also implicated in immune regulation and cellular adhesivity, displayed lower abundance in malaria patients. In addition, 37 proteins (adjusted p-values<0.05) were identified with increased levels in patients with severe compared to mild malaria. This set includes, proteins involved in tissue remodelling and erythrocyte membrane proteins. Collectively, this approach has been successfully used to identify proteins both with known and unknown association with different stages of malaria. Conclusion: In this study, a high-throughput affinity proteomics approach was used to find protein profiles in plasma linked to P. falciparum infection and malaria disease progression. The proteins presented herein are mainly involved in inflammatory response, cellular adhesion and as constituents of erythrocyte membrane. These findings have a great potential to provide increased conceptual understanding of host-parasite interaction and malaria pathogenesis.
|
|
| 8. |
- Adamo, Hanibal Hani, et al.
(författare)
-
Adaptive (TINT) Changes in the Tumor Bearing Organ Are Related to Prostate Tumor Size and Aggressiveness
- 2015
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:11
-
Tidskriftsartikel (refereegranskat)abstract
- In order to grow, tumors need to induce supportive alterations in the tumor-bearing organ, by us named tumor instructed normal tissue (TINT) changes. We now examined if the nature and magnitude of these responses were related to tumor size and aggressiveness. Three different Dunning rat prostate tumor cells were implanted into the prostate of immune-competent rats; 1) fast growing and metastatic MatLyLu tumor cells 2) fast growing and poorly metastatic AT-1 tumor cells, and 3) slow growing and non-metastatic G tumor cells. All tumor types induced increases in macrophage, mast cell and vascular densities and in vascular cell-proliferation in the tumor-bearing prostate lobe compared to controls. These increases occurred in parallel with tumor growth. The most pronounced and rapid responses were seen in the prostate tissue surrounding MatLyLu tumors. They were, also when small, particularly effective in attracting macrophages and stimulating growth of not only micro-vessels but also small arteries and veins compared to the less aggressive AT-1 and G tumors. The nature and magnitude of tumor-induced changes in the tumor-bearing organ are related to tumor size but also to tumor aggressiveness. These findings, supported by previous observation in patient samples, suggest that one additional way to evaluate prostate tumor aggressiveness could be to monitor its effect on adjacent tissues.
|
|
| 9. |
- Adamo, Hanibal Hani, et al.
(författare)
-
Characterization of a Gene Expression Signature in Normal Rat Prostate Tissue Induced by the Presence of a Tumor Elsewhere in the Organ
- 2015
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:6
-
Tidskriftsartikel (refereegranskat)abstract
- Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating changes in the tumor-bearing organ, for example growth of the vasculature, an altered extracellular matrix, and influx of inflammatory cells. To investigate this response further, we compared prostate morphology and the gene expression profile of tumor-bearing normal rat prostate tissue (termed tumor-instructed/indicating normal tissue (TINT)) with that of prostate tissue from controls. Dunning rat AT-1 prostate cancer cells were injected into rat prostate and tumors were established after 10 days. As controls we used intact animals, animals injected with heat-killed AT-1 cells or cell culture medium. None of the controls showed morphological TINT-changes. A rat Illumina whole-genome expression array was used to analyze gene expression in AT-1 tumors, TINT, and in medium injected prostate tissue. We identified 423 upregulated genes and 38 downregulated genes (p<0.05, >= 2-fold change) in TINT relative to controls. Quantitative RT-PCR analysis verified key TINT-changes, and they were not detected in controls. Expression of some genes was changed in a manner similar to that in the tumor, whereas other changes were exclusive to TINT. Ontological analysis using GeneGo software showed that the TINT gene expression profile was coupled to processes such as inflammation, immune response, and wounding. Many of the genes whose expression is altered in TINT have well-established roles in tumor biology, and the present findings indicate that they may also function by adapting the surrounding tumor-bearing organ to the needs of the tumor. Even though a minor tumor cell contamination in TINT samples cannot be ruled out, our data suggest that there are tumor-induced changes in gene expression in the normal tumor-bearing organ which can probably not be explained by tumor cell contamination. It is important to validate these changes further, as they could hypothetically serve as novel diagnostic and prognostic markers of prostate cancer.
|
|
| 10. |
- Adamo, Hanibal Hani, 1984-, et al.
(författare)
-
Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome
- 2019
-
Ingår i: The Prostate. - : John Wiley & Sons. - 0270-4137 .- 1097-0045. ; 79:5, s. 435-445
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein- (C/EBP).Methods: To explore this further, we examined C/EBP expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors?and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.Results: In rats, C/EBP mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBP was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBP expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBP in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBP in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome.Conclusions: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.
|
|
| 11. |
- Adamo, Hanibal, et al.
(författare)
-
Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of a tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein-β (C/EBPβ). To explore this further, we examined C/EBPβ expression by quantitative RT-PCR, immunohistochemistry, and western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors―and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.In rats, C/EBPβ mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBPβ was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBPβ expression in the tumor-bearing prostates was associated with tumor size, with distance to the tumor, and with tumor cell metastatic capacity.In prostate cancer patients, high expression of C/EBPβ in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and a favorable outcome. High expression of C/EBPβ in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, the presence of metastases at diagnosis, and poor outcome.
|
|
| 12. |
- Ahlgren, Karin, et al.
(författare)
-
De stora restaureringarna : Från Uppsala domkyrka till Skokloster
- 2004
-
Rapport (populärvet., debatt m.m.)abstract
- De stora restaureringarna har varit årets tema. Genom att dokumentera och analysera teori och praktik i några av 1800- och 1900-talets största restaureringar - från genomgripande stilrestaureringar till ett mer återhållsamt och tekniskt skonsamt synsätt. Därmed får vi också ett bättre underlag även för dagens ställningstagande.Föremål för våra studier är Uppsala domkyrka, Gripsholms slott, Vreta klosterkyrka, Gustav 11I:s paviljong i Haga, Kungapalatset i Vadstena och Skoklosters slott. Vi hoppas att denna utställning skall bidra till en kritisk hållning och en ökad kunskap om restaureringskonsten, som kvalificerad yrkesuppgift, tidsspegel för historiesyn och som gestaltningsideal.
|
|
| 13. |
- Alhouayek, Mireille, et al.
(författare)
-
Effects of orthotopic implantation of rat prostate tumour cells upon components of the N-acylethanolamine and monoacylglycerol signalling systems : an mRNA study
- 2020
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- There is good evidence that the N-acylethanolamine (NAE)/monoacylglycerol (MAG) signalling systems are involved in the pathogenesis of cancer. However, it is not known how prostate tumours affect these systems in the surrounding non-malignant tissue and vice versa. In the present study we have investigated at the mRNA level 11 components of these systems (three coding for anabolic enzymes, two for NAE/MAG targets and six coding for catabolic enzymes) in rat prostate tissue following orthotopic injection of low metastatic AT1 cells and high metastatic MLL cells. The MLL tumours expressed higher levels of Napepld, coding for a key enzyme in NAE synthesis, and lower levels of Naaa, coding for the NAE hydrolytic enzyme N-acylethanolamine acid amide hydrolase than the AT1 tumours. mRNA levels of the components of the NAE/MAG signalling systems studied in the tissue surrounding the tumours were not overtly affected by the tumours. AT1 cells in culture expressed Faah, coding for the NAE hydrolytic enzyme fatty acid amide hydrolase, at much lower levels than Naaa. However, the ability of the intact cells to hydrolyse the NAE arachidonoylethanolamide (anandamide) was inhibited by an inhibitor of FAAH, but not of NAAA. Treatment of the AT1 cells with interleukin-6, a cytokine known to be involved in the pathogenesis of prostate cancer, did not affect the expression of the components of the NAE/MAG system studied. It is thus concluded that in the model system studied, the tumours show different expressions of mRNA coding for key the components of the NAE/MAG system compared to the host tissue, but that these changes are not accompanied by alterations in the non-malignant tissue.
|
|
| 14. |
- Altgärde, Noomi, 1983, et al.
(författare)
-
Mucin-like region of herpes simplex virus type 1 attachment protein gC modulates the virus-glycosaminoglycan interaction.
- 2015
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 290:35, s. 21473-21485
-
Tidskriftsartikel (refereegranskat)abstract
- Glycoprotein C (gC) mediates the attachment of herpes simplex virus type 1 (HSV-1) to susceptible host cells by interacting with glycosaminoglycans (GAGs) on the cell surface. gC contains a mucin-like region located near the GAG-binding site, which may affect the binding activity. Here, we address this issue by studying an HSV-1 mutant lacking the mucin- like domain in gC and the corresponding purified mutant protein (gCΔmuc), in cell culture and GAG-binding assays, respectively. The mutant virus exhibited two functional alterations as compared to native HSV-1, i.e. decreased sensitivity to GAG-based inhibitors of virus attachment to cells, and reduced release of viral particles from the surface of infected cells. Kinetic and equilibrium binding characteristics of purified gC were assessed using surface plasmon resonance-based sensing together with a surface platform consisting of end-on immobilized GAGs. Both native gC and gCΔmuc bound via the expected binding region to chondroitin sulfate and sulfated hyaluronan but not to the non-sulfated hyaluronan, confirming binding specificity. In contrast to native gC, gCΔmuc exhibited a decreased affinity for GAGs and a slower dissociation, indicating that once formed, the gCΔmuc-GAG complex is more stable. It was also found that a larger number of gCΔmuc bound to a single GAG chain, compared to native gC. Taken together, our data suggest that the mucin-like region of HSV-1 gC is involved in the modulation of the GAG-binding activity, a feature of importance both for unrestricted virus entry into the cells and release of newly produced viral particles from infected cells.
|
|
| 15. |
- Alvebratt, Caroline
(författare)
-
Advanced Methods for Evaluation of the Performance of Complex Drug Delivery System
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Low oral bioavailability of drugs originating from poor aqueous solubility is a common issue in drug development. Various enabling formulations have been presented to circumvent this limitation, many making use of supersaturation. In these, the drug is delivered to the gastro-intestinal lumen in a high energy state e.g. in amorphous form or a liquid lipid vehicle. Concentrations surpassing the equilibrium solubility of the crystalline drug are achieved, which facilitate increased absorption for dissolution-rate limited compounds. Meanwhile the use of the enabling formulation can be beneficial to increase the bioavailability of poorly water-soluble drugs, in vitro evaluation of these systems remain challenging. Limited methods have also evaluated several different types of enabling formulation in the same experimental setup. The overall aim of this thesis was therefore to develop assays to study the performance of various complex drug delivery systems. In the first part, a small scale dissolution apparatus, the µDiss Profiler, was used to study drug release from drug-loaded mesoporous magnesium carbonate (MMC). A protective filter was developed to minimize particle interference on the UV-measurements, enabling studies of supersaturation from the amorphous carrier. In the second paper, lipids were adsorbed onto the MMC. A modified in vitro lipolysis setup was established and the samples were analyzed with nuclear magnetic resonance spectroscopy. A stability study of the lipid-loaded MMC was also performed. The methods developed in the first two projects provided an insight to events occurring in the intestinal lumen. The intestinal absorption has however been shown to be a complex interplay between dissolution-digestion and permeation. In the final two projects, two devices comprising of a donor (luminal) chamber and a receiver (serosal) chamber were studied (the µFLUX and the enabling absorption, ENA, device). The two chambers were separated by a semipermeable membrane (cell-based and/or phospholipid-based). A wide range of enabling formulations were evaluated in the two assays. As the exposure in the donor correlated poorly with the exposure in the receiver compartment, this emphasizes the importance of in vitro methods taking both the dissolution-digestion and permeation into account. The ENA results also predicted the in vivo performance in rats well. To conclude, several models have been established in the thesis to study the in vitro performance of enabling formulations, which will be valuable for screening of appropriate drug delivery systems.
|
|
| 16. |
|
|
| 17. |
- Andersson, Ulrika, 1977, et al.
(författare)
-
Västsvenska SOM-undersökningen 2016 - Uppföljning av Vision Västra götaland : SOM-rapport nr 2017:40
- 2017
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Som en del i utvärderingen av hur väl visioner och målsättningar för Västra Götaland uppnås, har den här rapporten fokuserat på en rad frågor som tillsammans speglar de vanor och attityder som finns hos invånarna i regionen. Med utgångspunkt i 2016 års västsvenska SOM-undersökning har medborgarnas demokratisyn, förtroende för politiker, utvärdering av Västra Götalandsregionens prestationer samt åsikter om infrastruktur och sjukvård kartlagts på detaljerad nivå. Vidare har invånarnas arbetsliv, livsstil och självskattade hälsa analyserats. Resultaten visar på många likheter i regionen men också på stora olikheter, varav många är direkt kopplade till socioekonomiska faktorer, utbildning och ålder. I detta avslutande kapitel sammanfattas och relateras rapportens resultat till Vision Västra Götaland – det goda livet.
|
|
| 18. |
- Andresen Bergström, Moa, 1978, et al.
(författare)
-
Oximes: Metabolic Activation and Structure−Allergenic Activity Relationships
- 2008
-
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 51:8, s. 2541-2550
-
Tidskriftsartikel (refereegranskat)abstract
- Metabolic activation of chemicals (prohaptens) in the skin can cause allergic contact dermatitis. We have explored structure−allergenic activity relationships for seven potential oxime prohaptens using the local lymph node assay and a GSH trapping screen with liver microsomes. The general structure−allergenic activity relationships found were that an α,β-unsaturation is necessary for an oxime to be a prohapten and that increased steric hindrance around this double bond leads to reduction in sensitizing capacity. We also found that sensitizing oximes can be distinguished in vitro from nonsensitizers by monitoring of mono-oxidized (+16 Da) GSH conjugates in the GSH trapping screen. However, care should be taken when interpreting data from GSH trapping screens, as nonsensitizers may also form GSH conjugates via alternative mechanisms. This investigation emphasizes the importance of considering cutaneous bioactivation in toxicity assessment of chemicals used in contact with the skin.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Bauer, Brigitte, 1978, et al.
(författare)
-
Modification and expulsion of keratins by human epidermal keratinocytes upon hapten exposure in vitro.
- 2011
-
Ingår i: Chemical research in toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X. ; 24:5, s. 737-43
-
Tidskriftsartikel (refereegranskat)abstract
- Allergic contact dermatitis is the most prevalent form of human immunotoxicity. It is caused by reactive low molecular weight chemicals, that is, haptens, coming in contact with the skin where hapten-peptide complexes are formed, activating the immune system. By using sensitizing fluorescent thiol-reactive haptens, that is, bromobimanes, we show how keratinocytes respond to hapten exposure in vitro and reveal, for the first time in a living system, an exact site of haptenation. Rapid internalization and reaction of haptens with keratin filaments were visualized. Subsequently, keratinocytes respond in vitro to hapten exposure by release of membrane blebs, which contain haptenated keratins 5 and 14. Particularly, cysteine 54 of K5 was found to be a specific target. A mechanism is proposed where neoepitopes, otherwise hidden from the immune system, are released after hapten exposure via keratinocyte blebbing. The observed expulsion of modified keratins by keratinocytes in vitro might play a role during hapten sensitization in vivo and should be subject to further investigations.
|
|
| 23. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
-
Platelet proteome and function in X-linked thrombocytopenia with thalassemia and in silico comparisons with gray platelet syndrome
- 2021
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:11
-
Tidskriftsartikel (refereegranskat)abstract
- In X-linked thrombocytopenia with thalassemia (XLTT; OMIM 314050), caused by the mutation p.R216Q in exon 4 of the GATA1 gene, male hemizygous patients display macrothrombocytopenia, bleeding diathesis and a β-thalassemia trait. Herein, we describe findings in two unrelated Swedish XLTT families with a bleeding tendency exceeding what is expected from the thrombocytopenia. Blood tests revealed low P-PAI-1 and P-factor 5, and elevated S-thrombopoietin levels. Transmission electron microscopy showed diminished numbers of platelet α- and dense granules. The proteomes of isolated blood platelets from 5 male XLTT patients, compared to 5 gender- and age matched controls, were explored. Quantitative mass spectrometry showed alterations of 83 proteins (fold change ≥±1.2, q< .05). Of 46 downregulated proteins, 39 were previously reported to be associated with platelet granules. Reduced protein levels of PTGS1 and SLC35D3 were validated in megakaryocytes of XLTT bone marrow biopsies by immunohistochemistry. Platelet function testing by flow cytometry revealed low dense- and α-granule release and fibrinogen binding in response to ligation of receptors for ADP, the thrombin receptor PAR4 and the collagen receptor GPVI. Significant reductions of a number of α-granule proteins overlapped with a previous platelet proteomics investigation in the inherited macrothrombocytopenia gray platelet syndrome (GPS). In contrast, Ca2+ transporter proteins that facilitate dense granule release were downregulated in XLTT but upregulated in GPS. Ingenuity Pathway Analysis showed altered Coagulation System and Protein Ubiquitination pathways in the XLTT platelets. Collectively, the results revealed protein and functional alterations affecting platelet α- and dense granules in XLTT, probably contributing to bleeding.
|
|
| 24. |
- Bergström, Annika, et al.
(författare)
-
Towards rising inequalities in newspaper and television news consumption? : A longitudinal analysis
- 2019
-
Ingår i: European Journal of Communication. - : SAGE Publications. - 0267-3231 .- 1460-3705. ; 34:2, s. 175-189
-
Tidskriftsartikel (refereegranskat)abstract
- The transformation from low- to high-choice media environments has triggered concerns of rising inequalities in news media use. This concern has been buttressed by research showing that motivational factors have become more important predictors of news media use. Less attention has been paid to how changes in media environments have altered the impact of socioeconomic status on news media use. Hence, the purpose of this study is to investigate the changing impact of socioeconomic status on newspaper and television news consumption, empirically focussing on Sweden between 2000 and 2016. Among other things, results suggest that the impact of socioeconomic status on news media use has increased with respect to reading morning newspapers but decreased for reading tabloids and watching television news.
|
|
| 25. |
- Bergström, Annika, 1964, et al.
(författare)
-
Towards rising inequalities in newspaper and television news consumption? A longitudinal analysis, 2000–2016
- 2019
-
Ingår i: European Journal of Communication. - : SAGE Publications. - 0267-3231 .- 1460-3705. ; 34:2, s. 175-189
-
Tidskriftsartikel (refereegranskat)abstract
- The transformation from low- to high-choice media environments has triggered concerns of rising inequalities in news media use. This concern has been buttressed by research showing that motivational factors have become more important predictors of news media use. Less attention has been paid to how changes in media environments have altered the impact of socioeconomic status on news media use. Hence, the purpose of this study is to investigate the changing impact of socioeconomic status on newspaper and television news consumption, empirically focussing on Sweden between 2000 and 2016. Among other things, results suggest that the impact of socioeconomic status on news media use has increased with respect to reading morning newspapers but decreased for reading tabloids and watching television news.
|
|
| 26. |
- Bergström, Lena, et al.
(författare)
-
Biodiversitet och ekosystemtjänster i kustområden
- 2021
-
Ingår i: Biologisk mångfald, naturnyttor och ekosystemtjänster. - : Sveriges Lantbruksuniversitet. - 9789188083357 - 9789188083364 - 9789162013073 ; , s. 209-219
-
Bokkapitel (refereegranskat)
|
|
| 27. |
- Bergström, Sofia, et al.
(författare)
-
A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers : a GENFI study
- 2021
-
Ingår i: Molecular Neurodegeneration. - : Springer Nature. - 1750-1326. ; 16:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background A detailed understanding of the pathological processes involved in genetic frontotemporal dementia is critical in order to provide the patients with an optimal future treatment. Protein levels in CSF have the potential to reflect different pathophysiological processes in the brain. We aimed to identify and evaluate panels of CSF proteins with potential to separate symptomatic individuals from individuals without clinical symptoms (unaffected), as well as presymptomatic individuals from mutation non-carriers. Methods A multiplexed antibody-based suspension bead array was used to analyse levels of 111 proteins in CSF samples from 221 individuals from families with genetic frontotemporal dementia. The data was explored using LASSO and Random forest. Results When comparing affected individuals with unaffected individuals, 14 proteins were identified as potentially important for the separation. Among these, four were identified as most important, namely neurofilament medium polypeptide (NEFM), neuronal pentraxin 2 (NPTX2), neurosecretory protein VGF (VGF) and aquaporin 4 (AQP4). The combined profile of these four proteins successfully separated the two groups, with higher levels of NEFM and AQP4 and lower levels of NPTX2 in affected compared to unaffected individuals. VGF contributed to the models, but the levels were not significantly lower in affected individuals. Next, when comparing presymptomatic GRN and C9orf72 mutation carriers in proximity to symptom onset with mutation non-carriers, six proteins were identified with a potential to contribute to a separation, including progranulin (GRN). Conclusion In conclusion, we have identified several proteins with the combined potential to separate affected individuals from unaffected individuals, as well as proteins with potential to contribute to the separation between presymptomatic individuals and mutation non-carriers. Further studies are needed to continue the investigation of these proteins and their potential association to the pathophysiological mechanisms in genetic FTD.
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
- Bergström, Sofia, et al.
(författare)
-
Multi-cohort profiling reveals elevated CSF levels of brain-enriched proteins in Alzheimer's disease
- 2021
-
Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 8:7, s. 1456-1470
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Decreased amyloid beta (A beta) 42 together with increased tau and phospho-tau in cerebrospinal fluid (CSF) is indicative of Alzheimer's disease (AD). However, the molecular pathophysiology underlying the slowly progressive cognitive decline observed in AD is not fully understood and it is not known what other CSF biomarkers may be altered in early disease stages. Methods: We utilized an antibody-based suspension bead array to analyze levels of 216 proteins in CSF from AD patients, patients with mild cognitive impairment (MCI), and controls from two independent cohorts collected within the AETIONOMY consortium. Two additional cohorts from Sweden were used for biological verification. Results: Six proteins, amphiphysin (AMPH), aquaporin 4 (AQP4), cAMP-regulated phosphoprotein 21 (ARPP21), growth-associated protein 43 (GAP43), neurofilament medium polypeptide (NEFM), and synuclein beta (SNCB) were found at increased levels in CSF from AD patients compared with controls. Next, we used CSF levels of A beta 42 and tau for the stratification of the MCI patients and observed increased levels of AMPH, AQP4, ARPP21, GAP43, and SNCB in the MCI subgroups with abnormal tau levels compared with controls. Further characterization revealed strong to moderate correlations between these five proteins and tau concentrations. Interpretation: In conclusion, we report six extensively replicated candidate biomarkers with the potential to reflect disease development. Continued evaluation of these proteins will determine to what extent they can aid in the discrimination of MCI patients with and without an underlying AD etiology, and if they have the potential to contribute to a better understanding of the AD continuum.
|
|
| 31. |
|
|
| 32. |
- Bergström, Sofia
(författare)
-
Multiplexed antibody-based protein profiling in the pursuit of CSF biomarkers for neurodegenerative diseases
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is a desire for a transition from generic treatments designed for the average patient, towards more individual-based precision medicine. An increased knowledge about disease pathophysiology on a molecular level would be beneficial for this transition. The study of proteins can contribute with valuable insights into etiology and pathogenesis of different diseases and thereby aid the clinical assessment of patients and guide future treatments.Neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia, are characterized by a progressive loss of function, and eventually death of neurons. Neurons allow the brain to communicate with the rest of the body, and a deteriorated function of neurons can result in problems with mobility or mental functions. Neurodegenerative diseases progress slowly over many years, with a long silent asymptomatic phase before symptom onset. It is hard to rebuild what is already lost, but disease-modifying treatments might be able to slow down or halt the deterioration of the brain. Therefore, there is a major research focus on investigating the early stages of disease pathogenesis in order to elucidate this critical phase in disease progression.The four papers included in this thesis focus on identifying altered protein profiles in cerebrospinal fluid from patients with neurodegenerative diseases. For this purpose, multiplexed antibody-based suspension bead arrays have been used. This method allows for hundreds of proteins to be analyzed in hundreds of samples in the same assay. Paper I focuses on Alzheimer’s disease and investigates the profiles of 200 proteins when comparing patients with controls. Six proteins were identified at altered levels and were further investigated in relation to the progression from mild cognitive impairment to Alzheimer’s disease. Paper II explores 100 protein profiles in relation to the core Alzheimer’s disease biomarkers in asymptomatic 70-year-olds to elucidate patterns preceding potential disease onset. Paper III investigates the transition to cognitive impairment in patients with Parkinson’s disease and explores potential associations between protein profiles and cognitive assessment tests. Finally, Paper IV explores panels of proteins in the context of frontotemporal dementia. Panels of proteins, instead of single biomarkers, have an increased potential to capture the range of biological processes within these types of complex and multifactorial diseases.Neurodegenerative diseases are often heterogeneous which puts high demands on the study design including an appropriate selection of study population. However, significant similarities are also present which makes it advantageous to have a broad perspective and work with several neurodegenerative disorders. This thesis presents the results from multiplexed antibody-based protein profiling as a contribution to a better understanding of neurodegenerative diseases.
|
|
| 33. |
|
|
| 34. |
- Bergström, Ulf, et al.
(författare)
-
Inför fler fiskefria områden för att skydda bestånd och ekosystem
- 2024
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Fiskefria områden kan vara ett effektivt verktyg för att skydda både fisk- och kräftdjursbestånd och marina ekosystem. Men det är viktigt att områdena utformas på rätt sätt och är tillräckligt stora. Lektidsfredade områden kan vara enklare att driva igenom, men ger inte lika goda effekter.
|
|
| 35. |
- Bernberg, Evelina, 1981, et al.
(författare)
-
Repeated exposure to stressors do not accelerate atherosclerosis in ApoE-/- mice
- 2009
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 204:1, s. 90-95
-
Tidskriftsartikel (refereegranskat)abstract
- Psychosocial stress is suggested to play a significant role in development of cardiovascular disease. To evaluate the effects of repeated exposure to stress on atherosclerosis in atherosclerosis-prone ApoE(-/-) mice we used five different stressors. We further sought to determine whether stress combined with high salt diet induces dysfunctional neurohormonal regulation and impaired salt excretion, thus amplifying the atherogenic potential of salt. The five stressors were evaluated in male C57BL/6 mice and ApoE(-/-) mice (studies I and II) and then used in female ApoE(-/-) mice to study their effect on atherosclerosis (study III). The mice in study III received standard or high salt diet (8%) alone or in combination with stress for 12 weeks. Urine and plasma were collected for corticosterone and lipid analysis, respectively. Acute blood pressure (BP) and heart rate (HR) responses to stress were measured using telemetry. Plaque burden was assessed in the thoracic aorta and aortic root. Plaque morphology was investigated regarding macrophages and collagen content. Urinary corticosterone chronically increased in stressed mice (P<0.05 control vs. stress, P<0.05 control salt vs. stress salt). BP and HR increased acutely during all stressors (P<0.05). Body weight gain decreased significantly in the stress group (P<0.05 vs. control). However, stress did not alter plasma lipid levels, plaque area or plaque morphology. Increased BP and HR suggest an acute stress-related response in ApoE(-/-) mice. Furthermore, stress chronically decreased body weight gain and increased urinary corticosterone levels. Notably, despite an apparent stress effect, stress affected neither atherogenesis nor plaque morphology.
|
|
| 36. |
- Blomberg, Staffan, et al.
(författare)
-
Barn och socialt arbete : Socialhögskolans årsbok 2019
- 2020
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Årsboken ger en inblick i delar av den forskning kring socialt arbete med barn som sker vid Socialhögskolan. Den ger också en kort introduktion till verksamheten vid Socialhögskolan.
|
|
| 37. |
- Boqvist, Sofia, et al.
(författare)
-
Prevalence of Antibody to Six Leptospira Servovars in Swedish Wild Boars
- 2012
-
Ingår i: Journal of Wildlife Diseases. - : Wildlife Disease Association. - 0090-3558 .- 1943-3700. ; 48, s. 492-496
-
Tidskriftsartikel (refereegranskat)abstract
- Zoonotic Leptospira bacteria are pathogens that may increase in importance with climate change. We investigated the prevalence of antibody to six Leptospira serovars (sv) in the Swedish wild boar (Sus scrofa) population, which is increasing in number and geographic distribution. The serovars we selected cause disease in pigs or may be of use as sentinel serovars to measure the potential spread in Swedish fauna. In total, 386 serum samples from wild boars collected between 2005 and 2007 were investigated using a microscopic agglutination test for Leptospira interrogans sv Bratislava strain Jez Bratislava, sv Icterohaemorrhagiae strain Kantorowicz, sv Pomona strain Pomona, Leptospira kirschneri sv Grippotyphosa strain Duyster, and Leptospira borgpetersenii sv Tarassovi strain Perepelitsin, and a domestic strain closely related to sv Sejroe. Twelve (3.1%) of the analyzed samples were antibody-positive. Of those, nine (2.3%) were positive for sv Bratislava and 0.8% for sv Icterohaemorrhagiae. All antibody-positive samples originated from areas where wild boars are reported to be common. We conclude that Leptospira infection is less common in Swedish wild boar than in continental Europe. However, we recommend continuous surveillance to follow the effects of climate change and an increasing wild boar population.
|
|
| 38. |
- Bradley, Frideborg, et al.
(författare)
-
Multi-omics analysis of the cervical epithelial integrity of women using depot medroxyprogesterone acetate
- 2022
-
Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 18:5
-
Tidskriftsartikel (refereegranskat)abstract
- Depot medroxyprogesterone acetate (DMPA) is an injectable hormonal contraceptive used by millions of women worldwide. However, experimental studies have associated DMPA use with genital epithelial barrier disruption and mucosal influx of human immunodeficiency virus (HIV) target cells. We explored the underlying molecular mechanisms of these findings. Ectocervical biopsies and cervicovaginal lavage (CVL) specimens were collected from HIV-seronegative Kenyan sex workers using DMPA (n = 32) or regularly cycling controls (n = 64). Tissue samples were assessed by RNA-sequencing and quantitative imaging analysis, whereas protein levels were measured in CVL samples. The results suggested a DMPA-associated upregulation of genes involved in immune regulation, including genes associated with cytokine-mediated signaling and neutrophil-mediated immunity. A transcription factor analysis further revealed DMPA-associated upregulation of RELA and NFKB1 which are involved in several immune activation pathways. Several genes significantly downregulated in the DMPA versus the control group were involved in epithelial structure and function, including genes encoding keratins, small proline-rich proteins, and cell-cell adhesion proteins. Pathway analyses indicated DMPA use was associated with immune activation and suppression of epithelium development, including keratinization and cornification processes. The cervicovaginal microbiome composition (Lactobacillus dominant and non-Lactobacillus dominant) had no overall interactional impact on the DMPA associated tissue gene expression. Imaging analysis verified that DMPA use was associated with an impaired epithelial layer as illustrated by staining for the selected epithelial junction proteins E-cadherin, desmoglein-1 and claudin-1. Additional staining for CD4(+) cells revealed a more superficial location of these cells in the ectocervical epithelium of DMPA users versus controls. Altered protein levels of SERPINB1 and ITIH2 were further observed in the DMPA group. Identification of specific impaired epithelial barrier structures at the gene expression level, which were verified at the functional level by tissue imaging analysis, illustrates mechanisms by which DMPA adversely may affect the integrity of the genital mucosa. Author summarySexual transmission accounts for the majority of all new HIV infections in women, and alterations to the mucosal environment of the female genital tract have been associated with an increase in the risk of acquiring HIV. Observational epidemiological studies have implied that the use of the injectable hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may be associated with increased HIV-acquisition. However, a prospective clinical study has not confirmed this association and the controversial findings are currently evaluated in the context of international reproductive health policies. Several studies using various model systems indicate that DMPA affects the integrity of the genital epithelial barrier as well as the mucosal immune system, but the exact mechanisms remain largely unknown. To characterize the effect of DMPA on the genital mucosal environment, we used a multi-omics approach to assess paired genital secretions and cervical tissue samples from long-term regular DMPA users living in Kenya. This unique cohort represents a population at risk of HIV infection in which DMPA is one of the most commonly used hormonal contraceptives. We identified impaired cervical epithelial barrier structures, including DMPA-associated reduction in the expression of cell-cell adhesion molecules, keratins, small proline-rich proteins and a thinner upper epithelial layer with more superficially located CD4(+) cells. Gene set enrichment pathway analyses indicated DMPA use was associated with immune activation and suppression of epithelium development including keratinization and cornification pathways. Protein analysis identified altered levels of selected anti-proteases. Our findings illustrate mechanisms by which DMPA adversely may affect the integrity of the genital mucosa.
|
|
| 39. |
- Börgeson, Emma, et al.
(författare)
-
Lipoxin A(4) inhibits porphyromonas gingivalis-induced aggregation and reactive oxygen species production by modulating neutrophil-platelet interaction and CD11b expression
- 2011
-
Ingår i: Infection and Immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 79:4, s. 1489-1497
-
Tidskriftsartikel (refereegranskat)abstract
- Porphyromonas gingivalis is an etiological agent that is strongly associated with periodontal disease, and it correlates with numerous inflammatory disorders, such as cardiovascular disease. Circulating bacteria may contribute to atherogenesis by promoting CD11b/CD18-mediated interactions between neutrophils and platelets, causing reactive oxygen species (ROS) production and aggregation. Lipoxin A(4) (LXA(4)) is an endogenous anti-inflammatory and proresolving mediator that is protective of inflammatory disorders. The aim of this study was to investigate the effect of LXA(4) on the P. gingivalis-induced activation of neutrophils and platelets and the possible involvement of Rho GTPases and CD11b/CD18 integrins. Platelet/leukocyte aggregation and ROS production was examined by lumiaggregometry and fluorescence microscopy. Integrin activity was studied by flow cytometry, detecting the surface expression of CD11b/CD18 as well as the exposure of the high-affinity integrin epitope, whereas the activation of Rac2/Cdc42 was examined using a glutathione S-transferase pulldown assay. The study shows that P. gingivalis activates Rac2 and Cdc42 and upregulates CD11b/CD18 and its high-affinity epitope on neutrophils, and that these effects are diminished by LXA(4). Furthermore, we found that LXA(4) significantly inhibits P. gingivalis-induced aggregation and ROS generation in whole blood. However, in platelet-depleted blood and in isolated neutrophils and platelets, LXA(4) was unable to inhibit either aggregation or ROS production, respectively. In conclusion, this study suggests that LXA(4) antagonizes P. gingivalis-induced cell activation in a manner that is dependent on leukocyte-platelet interaction, likely via the inhibition of Rho GTPase signaling and the downregulation of CD11b/CD18. These findings may contribute to new strategies in the prevention and treatment of periodontitis-induced inflammatory disorders, such as atherosclerosis.
|
|
| 40. |
- Börjesson, Stefan, 1979-, et al.
(författare)
-
Limited Dissemination of Extended-Spectrum β-Lactamase- and Plasmid-Encoded AmpC-Producing Escherichia coli from Food and Farm Animals, Sweden
- 2016
-
Ingår i: Emerging Infectious Diseases. - : U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. - 1080-6040 .- 1080-6059. ; 22:4, s. 634-640
-
Tidskriftsartikel (refereegranskat)abstract
- Extended-spectrum β-lactamase (ESBL)- and plasmid-encoded ampC (pAmpC)-producing Enterobacteriaceae might spread from farm animals to humans through food. However, most studies have been limited in number of isolates tested and areas studied. We examined genetic relatedness of 716 isolates from 4,854 samples collected from humans, farm animals, and foods in Sweden to determine whether foods and farm animals might act as reservoirs and dissemination routes for ESBL/pAmpC-producing Escherichia coli. Results showed that clonal spread to humans appears unlikely. However, we found limited dissemination of genes encoding ESBL/pAmpC and plasmids carrying these genes from foods and farm animals to healthy humans and patients. Poultry and chicken meat might be a reservoir and dissemination route to humans. Although we found no evidence of clonal spread of ESBL/pAmpC-producing E. coli from farm animals or foods to humans, ESBL/pAmpC-producing E. coli with identical genes and plasmids were present in farm animals, foods, and humans.
|
|
| 41. |
- Crisci, Elisa, et al.
(författare)
-
Complement opsonization promotes HSV-2 infection of human dendritic cells
- 2016
-
Ingår i: Journal of Virology. - : American society of microbiology. - 0022-538X .- 1098-5514. ; 90:10, s. 4939-4950
-
Tidskriftsartikel (refereegranskat)abstract
- Herpes virus type 2 (HSV2) is one of the most common sexually transmitted infections globally with a very high prevalence in many countries. During HSV2 infection viral particles become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. In genital mucosa, the primary target cells for HSV2 infection are epithelial cells, but resident immune cells such as dendritic cells (DCs) are also infected. The DCs are the activators of the ensuing immune responses directed against HSV2, and the aim of this study was to examine the effects opsonization of HSV2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV1 or HSV2 specific antibodies more or less abolished the HSV2 infection of DCs.Our results clearly demonstrate the importance of studying HSV2 infection under conditions that ensue in vivo, i.e. when the virions are covered in complement fragments and complement fragments and antibodies, as this will shape the infection and the subsequent immune response and needs to be further elucidated.IMPORTANCE: During HSV2 infection viral particles should become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. The dendritic cells are the activators of the immune responses directed against HSV2, and the aim of this study was to examine the effects of complement alone or complement and antibodies, on the HSV2 infection of dendritic cells and their ability to mount inflammatory and antiviral responses.Our results demonstrate that the presence of antibodies and complement in the genital environment can influence HSV2 infection under in vitro conditions that reflect the in vivo situation. We believe that our findings are highly relevant for the understanding of HSV2 pathogenesis.
|
|
| 42. |
- Dezfouli, Mahya, et al.
(författare)
-
Newborn Screening for Presymptomatic Diagnosis of Complement and Phagocyte Deficiencies
- 2020
-
Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- The clinical outcomes of primary immunodeficiencies (PIDs) are greatly improved by accurate diagnosis early in life. However, it is not common to consider PIDs before the manifestation of severe clinical symptoms. Including PIDs in the nation-wide newborn screening programs will potentially improve survival and provide better disease management and preventive care in PID patients. This calls for the detection of disease biomarkers in blood and the use of dried blood spot samples, which is a part of routine newborn screening programs worldwide. Here, we developed a newborn screening method based on multiplex protein profiling for parallel diagnosis of 22 innate immunodeficiencies affecting the complement system and respiratory burst function in phagocytosis. The proposed method uses a small fraction of eluted blood from dried blood spots and is applicable for population-scale performance. The diagnosis method is validated through a retrospective screening of immunodeficient patient samples. This diagnostic approach can pave the way for an earlier, more comprehensive and accurate diagnosis of complement and phagocytic disorders, which ultimately lead to a healthy and active life for the PID patients.
|
|
| 43. |
|
|
| 44. |
- Dillner, Joakim, et al.
(författare)
-
Antibodies to SARS-CoV-2 and risk of past or future sick leave
- 2021
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- The extent that antibodies to SARS-CoV-2 may protect against future virus-associated disease is unknown. We invited all employees (n=15,300) at work at the Karolinska University Hospital, Stockholm, Sweden to participate in a study examining SARS-Cov-2 antibodies in relation to registered sick leave. For consenting 12,928 healthy hospital employees antibodies to SARS-CoV-2 could be determined and compared to participant sick leave records. Subjects with viral serum antibodies were not at excess risk for future sick leave (adjusted odds ratio (OR) controlling for age and sex: 0.85 [95% confidence interval (CI) (0.85 (0.43-1.68)]. By contrast, subjects with antibodies had an excess risk for sick leave in the weeks prior to testing [adjusted OR in multivariate analysis: 3.34 (2.98-3.74)]. Thus, presence of viral antibodies marks past disease and protection against excess risk of future disease. Knowledge of whether exposed subjects have had disease in the past or are at risk for future disease is essential for planning of control measures.Trial registration: First registered on 02/06/20, ClinicalTrials.gov NCT04411576.
|
|
| 45. |
- Eckernäs, Emma, 1992, et al.
(författare)
-
N, N-dimethyltryptamine forms oxygenated metabolites via CYP2D6-an in vitro investigation
- 2023
-
Ingår i: Xenobiotica. - 0049-8254. ; 53:8-9, s. 515-522
-
Tidskriftsartikel (refereegranskat)abstract
- N, N-dimethyltryptamine (DMT) is a psychedelic compound that has shown potential in the treatment of depression. Aside from the primary role of monoamine oxidase A (MAO-A) in DMT metabolism, the metabolic pathways are poorly understood. Increasing this understanding is an essential aspect of ensuring safe and efficacious use of DMT. This work aimed to investigate the cytochrome 450 (CYP) mediated metabolism of DMT by incubating DMT with recombinant human CYP enzymes and human liver microsomes (HLM) followed by analysis using high-resolution mass spectrometry for metabolite identification.DMT was rapidly metabolised by CYP2D6, while stable with all other investigated CYP enzymes. The metabolism of DMT in HLM was reduced after inclusion of harmine and SKF-525A whereas quinidine did not affect the metabolic rate, likely due to MAO-A residues present in HLM. Analysis of the CYP2D6 incubates showed formation of mono-, di- and tri-oxygenated metabolites, likely as a result of hydroxylation on the indole core. More research is needed to investigate the role of this metabolic pathway in vivo and any pharmacological activity of the proposed metabolites. Our findings may impact on safety issues following intake of ayahuasca in slow CYP2D6 metabolizers or with concomitant use of CYP2D6 inhibitors.
|
|
| 46. |
|
|
| 47. |
- Edfeldt, Gabriella, et al.
(författare)
-
Distinct cervical tissue-adherent and luminal microbiome communities correlate with mucosal host gene expression and protein levels in Kenyan sex workers
- 2023
-
Ingår i: Microbiome. - : Springer Nature. - 2049-2618. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background The majority of studies characterizing female genital tract microbiota have focused on luminal organisms, while the presence and impact of tissue-adherent ectocervical microbiota remain incompletely understood. Studies of luminal and tissue-associated bacteria in the gastrointestinal tract suggest that these communities may have distinct roles in health and disease. Here, we performed a multi-omics characterization of paired luminal and tissue samples collected from a cohort of Kenyan female sex workers.Results We identified a tissue-adherent bacterial microbiome, with a higher alpha diversity than the luminal microbiome, in which dominant genera overall included Gardnerella and Lactobacillus, followed by Prevotella, Atopobium, and Sneathia. About half of the L. iners-dominated luminal samples had a corresponding Gardnerella-dominated tissue microbiome. Broadly, the tissue-adherent microbiome was associated with fewer differentially expressed host genes than the luminal microbiome. Gene set enrichment analysis revealed that L. crispatus-dominated tissue-adherent communities were associated with protein translation and antimicrobial activity, whereas a highly diverse microbial community was associated with epithelial remodeling and pro-inflammatory pathways. Tissue-adherent communities dominated by L. iners and Gardnerella were associated with lower host transcriptional activity. Tissue-adherent microbiomes dominated by Lactobacillus and Gardnerella correlated with host protein profiles associated with epithelial barrier stability, although with a more pro-inflammatory profile for the Gardnerella-dominated microbiome group. Tissue samples with a highly diverse composition had a protein profile representing cell proliferation and pro-inflammatory activity.Conclusion We identified ectocervical tissue-adherent bacterial communities in all study participants of a female sex worker cohort. These communities were distinct from cervicovaginal luminal microbiota in a significant proportion of individuals. We further revealed that bacterial communities at both sites correlated with distinct host gene expression and protein levels. The tissue-adherent bacterial community could possibly act as a reservoir that seed the lumen with less optimal, non-Lactobacillus, bacteria.
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
