| 1. |
- Gyllensten, Ulf B., et al.
(författare)
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Next Generation Plasma Proteomics Identifies High-Precision Biomarker Candidates for Ovarian Cancer
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. The aim of our study was to broadly measure protein biomarkers to find tests for the early detection of ovarian cancer. We found that combinations of 4-7 protein biomarkers can provide highly accurate detection of early- and late-stage ovarian cancer compared to benign conditions. The performance of the tests was then validated in a second independent cohort. Background: Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. Methods: We employed the Explore PEA technology for high-precision analysis of 1463 plasma proteins and conducted a discovery and replication study using two clinical cohorts of previously untreated patients with benign or malignant ovarian tumours (N = 111 and N = 37). Results: The discovery analysis identified 32 proteins that had significantly higher levels in malignant cases as compared to benign diagnoses, and for 28 of these, the association was replicated in the second cohort. Multivariate modelling identified three highly accurate models based on 4 to 7 proteins each for separating benign tumours from early-stage and/or late-stage ovarian cancers, all with AUCs above 0.96 in the replication cohort. We also developed a model for separating the early-stage from the late-stage achieving an AUC of 0.81 in the replication cohort. These models were based on eleven proteins in total (ALPP, CXCL8, DPY30, IL6, IL12, KRT19, PAEP, TSPAN1, SIGLEC5, VTCN1, and WFDC2), notably without MUCIN-16. The majority of the associated proteins have been connected to ovarian cancer but not identified as potential biomarkers. Conclusions: The results show the ability of using high-precision proteomics for the identification of novel plasma protein biomarker candidates for the early detection of ovarian cancer.
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| 2. |
- Ahrens,, Lutz, et al.
(författare)
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Screening av PFAS i grund- och ytvatten
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Levels of 26 per- and polyfluoroalkyl substances (PFASs) were measured in 502 water samples originat-ing from Swedish groundwater, surface water, sewage treatment plant (STP) effluents and landfill leachates. In drinking water source areas, the average Σ26PFAS concentration was 8.4 ng L-1. The national drinking water guideline value of 90 ng L-1 for Σ7PFASs was exceeded in 2% of these samples. In water not used for drinking water, Σ26PFASs average concentration was 142 ng L-1. PFOS concentra-tions exceeded the Annual Average Environmental Quality Standard (AA-EQS) of the EU Water Frame-work Directive in 42% of the surface water samples. Among the different water categories, the landfill leachates had the highest average concentration of Σ26PFAS with 487 ng L-1, followed by surface water (average 112 ng L-1), groundwater (49 ng L-1), STP effluents (35 ng L-1) and background screening lakes (3.4 ng L-1). The composition profile of the PFASs differed between the types of waters showing an even distribution of ΣPFCAs, ΣPFSAs and ΣPFAS precursors in groundwater, whereas in all other water categories, ΣPFCAs were dominant. As FOSA, PFNA, PFDA, and 6:2 FTSA were frequently detected in drinking water source areas (constituted 20%, 7.3%, 5.9%, and 4.4% of the Σ26PFASs, respectively), it is reasonable to consider the inclusion of these in the Swedish drinking water guideline.
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| 3. |
- Ahrens, Lutz, et al.
(författare)
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Screening of PFASs in groundwater and surface water
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Per- and polyfluoroalkyl substances (PFASs) are emerging organic pollutants characterized by their persistency, and bioaccumulation and toxicity potential. In this study, 26 PFASs were screened in 502 water samples originating from Swedish groundwater, surface water, sewage treatment plant (STP) effluents and landfill leachates. The objectives were to establish baseline concentrations of PFASs in the aquatic environment, to screen for potential sources, and to compare PFAS concentrations with guideline values for estimation of potential effects on the ecosystem and human health. In drinking water source areas, the average ∑26PFAS concentration was 8.4 ng L-1 with a median value of 0.6 ng L-1 (n = 172). The drinking water guideline value of 90 ng L-1 for ∑7PFASs (PFPeA, PFHxA, PFHpA, PFOA, PFBS, PFHxS, PFOS) established by the Swedish National Food Agency was exceeded in 4 samples (2% of the total number of samples in this category). In water not used for drinking water, ∑26PFASs concentrations were on average 142 ng L-1 (median 5.4 ng L-1). The high average PFAS concentrations can be explained by the fact that some samples showed extremely high PFAS concentrations with a maximum ∑26PFASs value of 12 900 ng L-1. In surface water, PFOS concentrations exceeded the annual average Environmental Quality Standard (AA-EQS) of the EU Water Framework Directive (WFD) in 42% of the samples. Among the different water categories, the landfill leachates had the highest average concentration of ∑26PFAS with 487 ng L-1 (median 435 ng L-1, n = 10), followed by surface water (average 112 ng L-1, median 4.1 ng L-1, n = 285), groundwater (average 49 ng L-1, median 0.4 ng L-1, n = 164), STP effluents (average 35 ng L-1, median 26 ng L-1; n = 13) and background screening lakes (remote lakes; average 3.4 ng L-1, median 1.4 ng L-1, n = 10). The composition profile of the PFASs differed between the types of waters showing an even distribution of ∑PFCAs, ∑PFSAs and ∑PFAS precursors in groundwater, whereas in all other water categories (surface water, background lakes, STP effluents and landfill leachates), ∑PFCAs were dominant. As FOSA, PFNA, PFDA, and 6:2 FTSA were frequently detected in drinking water source areas (constituted 20%, 7.3%, 5.9%, and 4.4% of the ∑26PFASs, respectively), it is reasonable to consider the inclusion of these in the Swedish drinking water guideline.
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| 4. |
- Aurell, Emelie, et al.
(författare)
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Mikroplaster : Redovisning av regeringsuppdrag om källor till mikroplaster och förslag på åtgärder för minskade utsläpp i Sverige
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I augusti 2015 fick Naturvårdsverket i uppdrag från regeringen att identifiera viktigare källor i Sverige till utsläpp av mikroplaster till havet och verka för att reducera utsläppen från dessa källor. I den här rapporten redovisar Naturvårdsverket uppdraget. Vi presenterar resultaten från den första, övergripande kartläggningen av källor till och spridning av mikroplaster i Sverige, en bedömning av vilka av de kartlagda källorna som primärt bör åtgärdas samt vilka steg som behöver tas för att förebygga utsläpp och minska spridning av mikroplaster till hav, sjöar och vattendrag från dessa källor.Förekomsten av mikroplast i den marina miljön har uppmärksammats allt mer under senare år, inte minst på global nivå. Mikroplast är ett samlingsnamn för små, små plastfragment (1 nm till 5 mm). De mikroplaster som hittats i världshaven, men även i sötvattensystem, har olika ursprung. Mikroplast kan bildas oavsiktligt när plastföremål slits och plastpartiklar frigörs, eller när vi inte återanvänder, återvinner eller slänger plastmaterial på rätt sätt utan plasten blir skräp som succesivt bryts ned till mindre och mindre bitar i naturen. Det finns också plast som från början tillverkas som små pellets eller korn.Utgångspunkten för arbetet har varit miljökvalitetsmålen Hav i balans samt levande kust och Levande sjöar och vattendrag samt målet om Giftfri miljö. Reduceradeutsläpp av mikroplaster till hav, sjöar och vattendrag bidrar till att nå dessa mål.Uppdraget har genomförts av Naturvårdsverket i samarbete med Havs- och vattenmyndigheten, andra berörda myndigheter, samt med deltagande av berörda organisationer och andra intressenter mellan augusti 2015 och maj 2017. Slutsatserna är Naturvårdsverkets egna.
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| 5. |
- Bauer, Ricarda M., et al.
(författare)
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Coupling of α1-adrenoceptors to ERK1/2 in the human prostate
- 2011
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Ingår i: Urologia internationalis. - : S. Karger AG. - 0042-1138 .- 1423-0399. ; 86:4, s. 427-433
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: α1-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further α1-adrenoceptor functions besides contraction. Here, we investigated whether α1-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2). METHODS: Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments. RESULTS: Stimulation of human prostate tissue with noradrenaline (30 μM) or phenylephrine (10 μM) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 μM) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126. CONCLUSIONS: α1-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of α1-adrenoceptors in the regulation of prostate growth.
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| 6. |
- Cheng, Arthur J., et al.
(författare)
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Intact single muscle fibres from SOD1(G93A) amyotrophic lateral sclerosis mice display preserved specific force, fatigue resistance and training-like adaptations
- 2019
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Ingår i: Journal of Physiology. - : Cambridge University Press. - 0022-3751 .- 1469-7793. ; 597:12, s. 3133-3146
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Tidskriftsartikel (refereegranskat)abstract
- Key points:How defects in muscle contractile function contribute to weakness in amyotrophic lateral sclerosis (ALS) were systematically investigated.Weakness in whole muscles from late stage SOD1G93A mice was explained by muscle atrophy as seen by reduced mass and maximal force.On the other hand, surviving single muscle fibres in late stage SOD1G93A have preserved intracellular Ca2+ handling, normal force-generating capacity and increased fatigue resistance.These intriguing findings provide a substrate for therapeutic interventions to potentiate muscular capacity and delay the progression of the ALS phenotype.Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by degeneration and loss of motor neurons, leading to severe muscle weakness and paralysis. The SOD1G93A mouse model of ALS displays motor neuron degeneration and a phenotype consistent with human ALS. The purpose of this study was to determine whether muscle weakness in ALS can be attributed to impaired intrinsic force generation in skeletal muscles. In the current study, motor neuron loss and decreased force were evident in whole flexor digitorum brevis (FDB) muscles of mice in the late stage of disease (125–150 days of age). However, in intact single muscle fibres, specific force, tetanic myoplasmic free [Ca2+] ([Ca2+]i), and resting [Ca2+]i remained unchanged with disease. Fibre-type distribution was maintained in late-stage SOD1G93A FDB muscles, but remaining muscle fibres displayed greater fatigue resistance compared to control and showed increased expression of myoglobin and mitochondrial respiratory chain proteins that are important determinants of fatigue resistance. Expression of genes central to both mitochondrial biogenesis and muscle atrophy where increased, suggesting that atrophic and compensatory adaptive signalling occurs simultaneously within the muscle tissue. These results support the hypothesis that muscle weakness in SOD1G93A is primarily attributed to neuromuscular degeneration and not intrinsic muscle fibre defects. In fact, surviving muscle fibres displayed maintained adaptive capacity with an exercise training-like phenotype, which suggests that compensatory mechanisms are activated that can function to delay disease progression.
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| 7. |
- Correia, Jorge C., et al.
(författare)
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Muscle-secreted neurturin couples myofiber oxidative metabolism and slow motor neuron identity
- 2021
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 33:11, s. 2215-2230
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Tidskriftsartikel (refereegranskat)abstract
- Endurance exercise promotes skeletal muscle vascularization, oxidative metabolism, fiber-type switching, and neuromuscular junction integrity. Importantly, the metabolic and contractile properties of the muscle fiber must be coupled to the identity of the innervating motor neuron (MN). Here, we show that muscle-derived neurturin (NRTN) acts on muscle fibers and MNs to couple their characteristics. Using a muscle-specific NRTN transgenic mouse (HSA-NRTN) and RNA sequencing of MN somas, we observed that retrograde NRTN signaling promotes a shift toward a slow MN identity. In muscle, NRTN increased capillary density and oxidative capacity and induced a transcriptional reprograming favoring fatty acid metabolism over glycolysis. This combination of effects on muscle and MNs makes HSA-NRTN mice lean with remarkable exercise performance and motor coordination. Interestingly, HSA-NRTN mice largely recapitulate the phenotype of mice with muscle-specific expression of its upstream regulator PGC-1a1. This work identifies NRTN as a myokine that couples muscle oxidative capacity to slow MN identity.
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| 8. |
- Elmhagen, Bodil, et al.
(författare)
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Interacting effects of change in climate, human population, land use, and water use on biodiversity and ecosystem services
- 2015
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Ingår i: Ecology and Society. - 1708-3087. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Human population growth and resource use, mediated by changes in climate, land use, and water use, increasingly impact biodiversity and ecosystem services provision. However, impacts of these drivers on biodiversity and ecosystem services are rarely analyzed simultaneously and remain largely unknown. An emerging question is how science can improve the understanding of change in biodiversity and ecosystem service delivery and of potential feedback mechanisms of adaptive governance. We analyzed past and future change in drivers in south-central Sweden. We used the analysis to identify main research challenges and outline important research tasks. Since the 19th century, our study area has experienced substantial and interlinked changes; a 1.6 degrees C temperature increase, rapid population growth, urbanization, and massive changes in land use and water use. Considerable future changes are also projected until the mid-21st century. However, little is known about the impacts on biodiversity and ecosystem services so far, and this in turn hampers future projections of such effects. Therefore, we urge scientists to explore interdisciplinary approaches designed to investigate change in multiple drivers, underlying mechanisms, and interactions over time, including assessment and analysis of matching-scale data from several disciplines. Such a perspective is needed for science to contribute to adaptive governance by constantly improving the understanding of linked change complexities and their impacts.
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| 9. |
- Gabrielle, Lunden, et al.
(författare)
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Play ontogeny in young chickens is affected by domestication and early stress
- 2022
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Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Play is common in young homeotherm animals and has an important role as a tentative indicator of positive states of welfare. Furthermore, during domestication play is believed to have increased in frequency in several species as part of the domestication syndrome. Here, we studied the ontogeny of play in chickens in two experiments. The first compared the behavioural development between domesticated White Leghorn (WL) laying hen chicks and ancestral Red Junglefowl (RJF) and the second compared the same between WL chicks that had experienced the stress of commercial hatchery routines and a control group, hatched under calm conditions. In both experiments, 10 groups of four chicks each from each of the groups were moved twice per week to an enriched and fully enclosed play arena, starting at day 8 and finishing day 39 or 53 after hatch. In the arena, the frequency of play behaviours was recorded during 30 min and divided into object, locomotory and social play. In experiment one, total play as well as object play was significantly more common in WL whereas locomotor and social play was more common in RJF. In experiment two, total play was significantly more frequent in commercially hatched chicks, despite that none of the sub-categories differed significantly between the groups. In conclusion, domestication as well as early stress does affect the occurrence of play in chickens, but the effects are complex and require further research.
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| 10. |
- Gao, Boya, et al.
(författare)
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The ‘migratory connectivity’ concept, and its applicability to insect migrants
- 2020
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Ingår i: Movement Ecology. - : Springer Science and Business Media LLC. - 2051-3933. ; 8:1
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Forskningsöversikt (refereegranskat)abstract
- Migratory connectivity describes the degree of linkage between different parts of an animal’s migratory range due to the movement trajectories of individuals. High connectivity occurs when individuals from one particular part of the migratory range move almost exclusively to another localized part of the migratory range with little mixing with individuals from other regions. Conversely, low migratory connectivity describes the situation where individuals spread over a wide area during migration and experience a large degree of mixing with individuals from elsewhere. The migratory connectivity concept is frequently applied to vertebrate migrants (especially birds), and it is highly relevant to conservation and management of populations. However, it is rarely employed in the insect migration literature, largely because much less is known about the migration circuits of most migratory insects than is known about birds. In this review, we discuss the applicability of the migratory connectivity concept to long-range insect migrations. In contrast to birds, insect migration circuits typically comprise multigenerational movements of geographically unstructured (non-discrete) populations between broad latitudinal zones. Also, compared to the faster-flying birds, the lower degree of control over movement directions would also tend to reduce connectivity in many insect migrants. Nonetheless, after taking account of these differences, we argue that the migratory connectivity framework can still be applied to insects, and we go on to consider postulated levels of connectivity in some of the most intensively studied insect migrants. We conclude that a greater understanding of insect migratory connectivity would be of value for conserving threatened species and managing pests.
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