| 1. |
- Gustafsson, Karin L., 1987, et al.
(författare)
-
The role of membrane ER alpha signaling in bone and other major estrogen responsive tissues
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogen receptor a (ER alpha) signaling leads to cellular responses in several tissues and in addition to nuclear ER alpha-mediated effects, membrane ER alpha (mER alpha) signaling may be of importance. To elucidate the significance, in vivo, of mER alpha signaling in multiple estrogen-responsive tissues, we have used female mice lacking the ability to localize ER alpha to the membrane due to a point mutation in the palmitoylation site (C451A), so called Nuclear-Only-ER (NOER) mice. Interestingly, the role of mER alpha signaling for the estrogen response was highly tissue-dependent, with trabecular bone in the axial skeleton being strongly dependent (>80% reduction in estrogen response in NOER mice), cortical and trabecular bone in long bones, as well as uterus and thymus being partly dependent (40-70% reduction in estrogen response in NOER mice) and effects on liver weight and total body fat mass being essentially independent of mER alpha (<35% reduction in estrogen response in NOER mice). In conclusion, mER alpha signaling is important for the estrogenic response in female mice in a tissue-dependent manner. Increased knowledge regarding membrane initiated ER alpha actions may provide means to develop new selective estrogen receptor modulators with improved profiles.
|
|
| 2. |
- Gustafsson, Stig-Inge, et al.
(författare)
-
ON YELLOW DISCOLORATIONS WHEN DRYING OAK, QUERCUS ROBUR
- 2008
-
Ingår i: DREWNO-WOOD. - Poznan, Poland : Instytut Technologii Drewna. - 1644-3985. ; 51:179, s. 29-44
-
Tidskriftsartikel (refereegranskat)abstract
- Growing trees many times contain more water than wood. When wood is to be utilized in the form of furniture it must therefore be dried in a kiln-dryer. In such a dryer the climate is very humid and warm which is ideal for many microorganisms such as bacteria and fungi. During their metabolism they change the chemical environment which sometimes lead to undisireable effects such as discolorations. In this paper we have examined specimen from oak, Quercus robur, collected from some parquet floor factories in Sweden. During drying some of these wood battens were affected with yellow streaks and spots which made the wood impossible to use for flooring. By examining small samples of the battens in light, as well as in scanning electron microscopes, we found that fungi grew inside the wooden tissue. By cultivation on agar plates we found several species where one has been identified as Penicillium roqueforti and another one as Paecilomyces variotii. We have also found that these fungi are extremely sensitive to high pH-values, so by spraying the wood with solutions of high pH already in the sawmill will probably make this problem much smaller.
|
|
| 3. |
- Lundqvist-Gustafsson, Helen, 1966-, et al.
(författare)
-
Dynamic Ca2+ changes in neutrophil phagosomes. A source for intracellular Ca2+ during phagolysosome formation?
- 2000
-
Ingår i: Cell Calcium. - : Elsevier BV. - 0143-4160 .- 1532-1991. ; 27:6, s. 353-362
-
Tidskriftsartikel (refereegranskat)abstract
- An increase in cytosolic Ca2+ concentration periphagosomally is critical for phagolysosomal formation and neutrophil elimination of microbes. The Ca2+ increase could be achieved through release of Ca2+ from mobilized intracellular stores. Alternatively, Ca2+ that passively enter the phagosome during phagocytosis could be provided by the phagosome. Intraphagosomal Ca2+ changes in single human neutrophils was measured during phagocytosis of serum opsonized Fura-2-conjugated zymosan particles, using a digital image processing system for microspectrofluorometry. A decrease in phagosomal Ca2+ down to nanomolar concentrations was seen within minutes following phagosomal closure. Blockage of plasma membrane Ca2+ channels by econazole abolished this decrease. The fluorescence properties of Fura-2 zymosan were retained after phagocytosis and stable to pH changes, reactive oxygen species, and proteolytic enzymes. We suggest that Ca2+ ions present in the phagosome enter the cell cytosol through Ca2+ channels in the phagosomal membrane, achieving a localized Ca2+ rise that is important for phagosome processing.
|
|
| 4. |
- Meier, H. E. Markus, et al.
(författare)
-
Assessment of Eutrophication Abatement Scenarios for the Baltic Sea by Multi-Model Ensemble Simulations
- 2018
-
Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- To assess the impact of the implementation of the Baltic Sea Action Plan (BSAP) on the future environmental status of the Baltic Sea, available uncoordinated multi-model ensemble simulations for the Baltic Sea region for the twenty-first century were analyzed. The scenario simulations were driven by regionalized global general circulation model (GCM) data using several regional climate system models and forced by various future greenhouse gas emission and air- and river-borne nutrient load scenarios following either reference conditions or the BSAP. To estimate uncertainties in projections, the largest ever multi-model ensemble for the Baltic Sea comprising 58 transient simulations for the twenty-first century was assessed. Data from already existing simulations from different projects including regionalized GCM simulations of the third and fourth assessment reports of the Intergovernmental Panel on Climate Change based on the corresponding Coupled Model Intercomparison Projects, CMIP3 and CMIP5, were collected.Various strategies to weigh the ensemble members were tested and the results for ensemble mean changes between future and present climates are shown to be robust with respect to the chosen metric. Although (1) the model simulations during the historical period are of different quality and (2) the assumptions on nutrient load levels during present and future periods differ between models considerably, the ensemble mean changes in biogeochemical variables in the Baltic proper with respect to nutrient load reductions are similar between the entire ensemble and a subset consisting only of the most reliable simulations.Despite the large spread in projections, the implementation of the BSAP will lead to a significant improvement of the environmental status of the Baltic Sea according to both weighted and unweighted ensembles. The results emphasize the need for investigating ensembles with many members and rigorous assessments of models’ performance.
|
|
| 5. |
- Meier, H. E. Markus, et al.
(författare)
-
Assessment of Uncertainties in Scenario Simulations of Biogeochemical Cycles in the Baltic Sea
- 2019
-
Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
-
Forskningsöversikt (refereegranskat)abstract
- Following earlier regional assessment studies, such as the Assessment of Climate Change for the Baltic Sea Basin and the North Sea Region Climate Change Assessment, knowledge acquired from available literature about future scenario simulations of biogeochemical cycles in the Baltic Sea and their uncertainties is assessed. The identification and reduction of uncertainties of scenario simulations are issues for marine management. For instance, it is important to know whether nutrient load abatement will meet its objectives of restored water quality status in future climate or whether additional measures are required. However, uncertainties are large and their sources need to be understood to draw conclusions about the effectiveness of measures. The assessment of sources of uncertainties in projections of biogeochemical cycles based on authors' own expert judgment suggests that the biggest uncertainties are caused by (1) unknown current and future bioavailable nutrient loads from land and atmosphere, (2) the experimental setup (including the spin up strategy), (3) differences between the projections of global and regional climate models, in particular, with respect to the global mean sea level rise and regional water cycle, (4) differing model-specific responses of the simulated biogeochemical cycles to long-term changes in external nutrient loads and climate of the Baltic Sea region, and (5) unknown future greenhouse gas emissions. Regular assessments of the models' skill (or quality compared to observations) for the Baltic Sea region and the spread in scenario simulations (differences among projected changes) as well as improvement of dynamical downscaling methods are recommended.
|
|
| 6. |
- Ohlsson, Claes, 1965, et al.
(författare)
-
The effects of estradiol are modulated in a tissue-specific manner in mice with inducible inactivation of ERα after sexual maturation.
- 2020
-
Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 318:5, s. 646-654
-
Tidskriftsartikel (refereegranskat)abstract
- Mouse models with lifelong inactivation of estrogen receptor α (ERα) show that ERα is the main mediator of estrogenic effects in bone, thymus, uterus, and fat. However, ERα inactivation early in life may cause developmental effects that confound the adult phenotypes. To address the specific role of adult ERα expression for estrogenic effects in bone and other non-skeletal tissues, we established a tamoxifen-inducible ERα-inactivated model by crossing CAG-Cre-ER and ERαflox/flox mice. Tamoxifen-induced ERα-inactivation after sexual maturation substantially reduced ERα mRNA levels in cortical bone, trabecular bone, thymus, uterus, gonadal fat, and hypothalamus, in CAG-Cre-ERαflox/flox (inducible ERαKO) compared to ERαflox/flox (control) mice. 17β-estradiol (E2) treatment increased trabecular bone volume fraction (BV/TV), cortical bone area and uterine weight, while it reduced thymus weight and fat mass in ovariectomized control mice. The estrogenic responses were substantially reduced in inducible ERαKO mice compared to control mice on BV/TV (-67%), uterine weight (-94%), thymus weight (-70%), and gonadal fat mass (-94%). In contrast, the estrogenic response on cortical bone area was unaffected in inducible ERαKO compared to control mice. In conclusion, using an inducible ERαKO model, not confounded by lack of ERa during development, we demonstrate that ERα expression in sexually mature female mice is required for normal E2 responses in most, but not all tissues. The finding that cortical, but not trabecular bone, responds normally to E2 treatment in inducible ERαKO mice strengthens the idea of cortical and trabecular bone being regulated by estrogen via different mechanisms.
|
|
| 7. |
- Turcot, Valerie, et al.
(författare)
-
Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
|
|
| 8. |
- Aldrin, Emilia, 1982-, et al.
(författare)
-
Socioonomastiska perspektiv på personnamn, djurnamn och företagsnamn : fem smärre studier
- 2017
-
Ingår i: Ortnamnssällskapet i Uppsala årsskrift. - Uppsala : Ortnamnssällskapet i Uppsala. - 0473-4351. ; , s. 5-13
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This article presents five undergraduate dissertations in socio-onomastics written by students from Halmstad University in 2016 and presented during a visit to the Department of Scandinavian Languages, Scandinavian Onomastics, at Uppsala University in 2017. Two of the dissertations deal with personal names (a social constructionist approach to personal names in children’s literature, and perceptions of name and identity among senior citizens). Two others focus on animal names in contemporary times (a gender analysis of names of horses, and a comparative analysis of names within different dog breeds). The last undergraduate dissertation concerns the process of naming companies.
|
|
| 9. |
|
|
| 10. |
- Bischoff, Juliane, et al.
(författare)
-
Source, transport and fate of soil organic matter inferred from microbial biomarker lipids on the East Siberian Arctic Shelf
- 2016
-
Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 13:17, s. 4899-4914
-
Tidskriftsartikel (refereegranskat)abstract
- The Siberian Arctic contains a globally significant pool of organic carbon (OC) vulnerable to enhanced warming and subsequent release by both fluvial and coastal erosion processes. However, the rate of release, its behaviour in the Arctic Ocean and vulnerability to remineralisation is poorly understood. Here we combine new measurements of microbial biohopanoids including adenosylhopane, a lipid associated with soil microbial communities, with published glycerol dialkyl glycerol tetraethers (GDGTs) and bulk delta C-13 measurements to improve knowledge of the fate of OC transported to the East Siberian Arctic Shelf (ESAS). The microbial hopanoid-based soil OC proxy R'(soil) ranges from 0.0 to 0.8 across the ESAS, with highest values nearshore and decreases offshore. Across the shelf R'(soil) displays a negative linear correlation with bulk delta C-13 measurements (r(2) = -0.73, p = < 0 : 001). When compared to the GDGT-based OC proxy, the branched and isoprenoid tetraether (BIT) index, a decoupled (non-linear) behaviour on the shelf was observed, particularly in the Buor-Khaya Bay, where the R'(soil) shows limited variation, whereas the BIT index shows a rapid decline moving away from the Lena River outflow channels. This reflects a balance between delivery and removal of OC from different sources. The good correlation between the hopanoid and bulk terrestrial signal suggests a broad range of hopanoid sources, both fluvial and via coastal erosion, whilst GDGTs appear to be primarily sourced via fluvial transport. Analysis of ice complex deposits (ICDs) revealed an average R'(soil) of 0.5 for the Lena Delta, equivalent to that of the Buor-Khaya Bay sediments, whilst ICDs from further east showed higher values (0.6-0.85). Although R'(soil) correlates more closely with bulk OC than the BIT, our understanding of the endmembers of this system is clearly still incomplete, with variations between the different East Siberian Arctic regions potentially reflecting differences in environmental conditions (e.g. temperature, pH), but other physiological controls on microbial bacteriohopanepolyol (BHP) production under psychrophilic conditions are as yet unknown.
|
|
| 11. |
- Bjoreland, Anders, et al.
(författare)
-
Liquid ionization chamber calibrated gel dosimetry in conformal stereotactic radiotherapy of brain lesions
- 2008
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 47:6, s. 1099-1109
-
Tidskriftsartikel (refereegranskat)abstract
- Hypofractionated conformal stereotactic radiotherapy (HCSRT) is an established method of treating brain lesions such as arteriovenous malformations (AVMs) and brain metastases. The aim of this study was to investigate the reliability of treatment plans in the terms of dose distribution and absorbed dose for HCSRT. Methods and materials. Treatment plans for three different clinical intracerebral targets, AVMs, were transferred to a CT study of a spherical water filled phantom simulating the human head and recalculated for the phantom geometry using a standard treatment planning system utilizing a pencil beam algorithm for dose calculation. The calculated absorbed dose, relative three dimensional (3D) dose distribution and dose conformity were investigated using gel dosimetry normalized to liquid ionization chamber (LIC) measurements. Results. The measured absorbed dose to the dose reference point was found to be within 2% of the calculated dose for all three targets. The measured dose distribution was found to be within 3% and 2 mm of the calculated dose for more than 93% of all points in the target volume for all three targets. Conclusions. The results show that the investigated standard treatment planning system can correctly predict the absorbed dose and dose distribution in different types of intracerebral targets and that the treatment can be delivered according to the plan.
|
|
| 12. |
|
|
| 13. |
- Bodin, Aase Katarina, 1977, et al.
(författare)
-
Influence of cultivation conditions on mechanical and morphological properties of bacterial cellulose tubes
- 2007
-
Ingår i: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 97:2, s. 425-434
-
Tidskriftsartikel (refereegranskat)abstract
- Bacterial cellulose (BC) was deposited in tubular form by fermenting Acetobacter xylinum on top of silicone tubes as an oxygenated support and by blowing different concns. of oxygen, i.e., 21% (air), 35%, 50%, and 100%. Mech. properties such as burst pressure and tensile properties were evaluated for all tubes. The burst pressure of the tubes increased with an increase in oxygen ratio and reached a top value of 880 mmHg at 100% oxygen. The Young's modulus was approx. 5 MPa for all tubes, irresp. of the oxygen ratio. The elongation to break decreased from 30% to 10-20% when the oxygen ratio was increased. The morphol. of the tubes was characterized by SEM (SEM). All tubes had an even inner side and a more porous outer side. The cross section indicated that the tubes are composed of layers and that the amt. of layers and the yield of cellulose increased with an increase in oxygen ratio. We propose that an internal vessel wall with high d. is required for the tube to sustain a certain pressure. An increase in wall thickness by an increase in oxygen ratio might explain the increasing burst pressure with increasing oxygen ratio. The fermn. method used renders it possible to produce branched tubes, tubes with unlimited length and inner diams. Endothelial cells (ECs) were grown onto the lumen of the tubes. The cells formed a confluent layer after 7 days. The tubes potential as a vascular graft is currently under investigation in a large animal model at the Center of Vascular Engineering, Sahlgrenska University Hospital, Gothenburg.
|
|
| 14. |
- Bondesson, Maria, et al.
(författare)
-
A CASCADE of effects of bisphenol A.
- 2009
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 28:4, s. 563-7
-
Tidskriftsartikel (refereegranskat)
|
|
| 15. |
- Bonnet, Timothee, et al.
(författare)
-
Genetic variance in fitness indicates rapid contemporary adaptive evolution in wild animals
- 2022
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 376:6596, s. 1012-1016
-
Tidskriftsartikel (refereegranskat)abstract
- The rate of adaptive evolution, the contribution of selection to genetic changes that increase mean fitness, is determined by the additive genetic variance in individual relative fitness. To date, there are few robust estimates of this parameter for natural populations, and it is therefore unclear whether adaptive evolution can play a meaningful role in short-term population dynamics. We developed and applied quantitative genetic methods to long-term datasets from 19 wild bird and mammal populations and found that, while estimates vary between populations, additive genetic variance in relative fitness is often substantial and, on average, twice that of previous estimates. We show that these rates of contemporary adaptive evolution can affect population dynamics and hence that natural selection has the potential to partly mitigate effects of current environmental change.
|
|
| 16. |
- Ceberg, Sofie, et al.
(författare)
-
Dosimetric verification of breathing adapted radiotherapy using polymer gel
- 2006
-
Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6596 .- 1742-6588. ; 56:1, s. 300-303
-
Konferensbidrag (refereegranskat)abstract
- In radiation therapy patient movement caused by respiration can be a major challenge to the ambition to deliver a high absorbed dose to the target volume while minimizing the dose to normal tissues. Large respiratory motion requires increased margins, which implies an increased risk of morbidity from late toxicity. It is therefore important to take respiratory motion into account when treating targets in the thorax region. The aim of this study was to investigate the feasibility of using a 3D gel dosimeter for dose verification of breathing adapted radiotherapy
|
|
| 17. |
- Ceberg, Sofie, et al.
(författare)
-
Modelling the dynamic dose response of an nMAG polymer gel dosimeter.
- 2012
-
Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 57:15, s. 4845-4853
-
Tidskriftsartikel (refereegranskat)abstract
- Gel dosimetry measures the absorbed radiation dose with high spatial resolution in 3D. However, recently published data show that the response of metacrylic-based polymer gels depends on the segmented delivery pattern, which could potentially be a considerable disadvantage for measurements of modern dynamic radiotherapy techniques. The aim of this study is to design a dynamic compartment model for the response of a gel dosimeter, exposed to an arbitrary irradiation pattern (segmented delivery and intensity modulation), in order to evaluate the associated effects on absorbed dose measurements. The model is based on the separation of the protons affecting the magnetic resonance signal (i.e. the R2 value) into six compartments, described by a set of differential equations. The model is used to calculate R2 values for a number of different segmented delivery patterns between 0-4 Gy over 1-33 fractions. Very good agreement is found between calculated and measured R2 values, with an average difference of 0.3 ± 1.1% (1 SD). The model is also used to predict the behaviour of a gel dosimeter exposed to irradiation according to typical IMRT, VMAT and respiratory gating scenarios. The calculated R2 values are approximately independent of the segmented delivery, given that the same total dose is delivered during the same total time. It is concluded that this study helps to improve the theoretical understanding of the dependence of metacrylic-based polymer gel response to segmented radiation delivery.
|
|
| 18. |
- Ceberg, Sofie, et al.
(författare)
-
RapidArc treatment verification in 3D using polymer gel dosimetry and Monte Carlo simulation.
- 2010
-
Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 55:17, s. 4885-4898
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to verify the advanced inhomogeneous dose distribution produced by a volumetric arc therapy technique (RapidArc) using 3D gel measurements and Monte Carlo (MC) simulations. The TPS (treatment planning system)-calculated dose distribution was compared with gel measurements and MC simulations, thus investigating any discrepancy between the planned dose delivery and the actual delivery. Additionally, the reproducibility of the delivery was investigated using repeated gel measurements. A prostate treatment plan was delivered to a 1.3 liter nPAG gel phantom using one single arc rotation and a target dose of 3.3 Gy. Magnetic resonance imaging of the gel was carried out using a 1.5 T scanner. The MC dose distributions were calculated using the VIMC-Arc code. The relative absorbed dose differences were calculated voxel-by-voxel, within the volume enclosed by the 90% isodose surface (VOI(90)), for the TPS versus gel and TPS versus MC. The differences between the verification methods, MC versus gel, and between two repeated gel measurements were investigated in the same way. For all volume comparisons, the mean value was within 1% and the standard deviation of the differences was within 2.5% (1SD). A 3D gamma analysis between the dose matrices were carried out using gamma criteria 3%/3 mm and 5%/5 mm (% dose difference and mm distance to agreement) within the volume enclosed by the 50% isodose surface (VOI(50)) and the 90% isodose surface (VOI(90)), respectively. All comparisons resulted in very high pass rates. More than 95% of the TPS points were within 3%/3 mm of both the gel measurement and MC simulation, both inside VOI(50) and VOI(90). Additionally, the repeated gel measurements showed excellent consistency, indicating reproducible delivery. Using MC simulations and gel measurements, this verification study successfully demonstrated that the RapidArc plan was both accurately calculated and delivered as planned.
|
|
| 19. |
- Ceberg, Sofie, et al.
(författare)
-
Tumor-tracking radiotherapy of moving targets; verification using 3D polymer gel, 2D ion-chamber array and biplanar diode array
- 2010
-
Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 250:1, s. 235-239
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to carry out a dosimetric verification of a dynamic multileaf collimator (DMLC)-based tumor-tracking delivery during respiratory-like motion. The advantage of tumor-tracking radiation delivery is the ability to allow a tighter margin around the target by continuously following and adapting the dose delivery to its motion. However, there are geometric and dosimetric uncertainties associated with beam delivery system constraints and output variations, and several investigations have to be accomplished before a clinical integration of this tracking technique. Two types of delivery were investigated in this study I) a single beam perpendicular to a target with a one dimensional motion parallel to the MLC moving direction, and II) an intensity modulated arc delivery (RapidArc®) with a target motion diagonal to the MLC moving direction. The feasibility study (I) was made using an 2D ionisation chamber array and a true 3D polymer gel. The arc delivery (II) was verified using polymer gel and a biplanar diode array. Good agreement in absorbed dose was found between delivery to a static target and to a moving target with DMLC tracking using all three detector systems. However, due to the limited spatial resolution of the 2D array a detailed comparison was not possible. The RapidArc® plan delivery was successfully verified using the biplanar diode array and true 3D polymer gel, and both detector systems could verify that the DMLC-based tumor-tracking delivery system has a very good ability to account for respiratory target motion.
|
|
| 20. |
- Ceberg, Sofie, et al.
(författare)
-
Verification of dynamic radiotherapy: the potential for 3D dosimetry under respiratory-like motion using polymer gel.
- 2008
-
Ingår i: Physics in Medicine and Biology. - 1361-6560. ; 53:20, s. 387-396
-
Tidskriftsartikel (refereegranskat)abstract
- Following the implementation of advanced treatment procedures in radiotherapy, there is a need for dynamic dose verification in 3D. Gel dosimetry could potentially be used for such measurements. However, recently published data show that certain types of gels have a dose rate and fractionation dependence. The aim of this study was to investigate the feasibility of using a polymer gel dosimeter for dose verification of dynamic radiotherapy. To investigate the influence of dose rate dependence during respiratory-like motion in and out of the beam, a respiration robot together with two types of gel systems (normoxic methacrylic acid gel (nMAG) and normoxic polyacrylamide gel (nPAG)) were used. Reference measurements were obtained using a linear diode array (LDA). Expected results, if there was no influence of the dose rate variation, were calculated by convolving the static irradiated gel data with the motion function controlling the robot. To investigate the fractionation dependence, the gels were irradiated using gated and ungated deliveries. Magnetic resonance imaging was used to evaluate the absorbed dose response of the gel. The measured gel data coincided well with the LDA data. Also, the calculated data agreed well with the measured dynamic gel data, i.e. no dose rate dependence due to motion was observed. The difference in the R2 response for the gels receiving ungated and gated, i.e. fractionated, deliveries was less than 1% for the nPAG and 4% for the nMAG, for absorbed doses up to 2 Gy. The maximum difference was 1.2% for the nPAG and 9% for the nMAG, which occurred at the highest given dose (4 Gy). The investigated gels were found to be feasible detectors for dose measurements under respiratory-like motion. For dose verification of dynamic RT involving gated delivery, e.g. breathing-adapted radiotherapy, relative absorbed dose evaluation should be used in order to minimize the effects of fractionated irradiation.
|
|
| 21. |
- Farman, Helen H., 1983, et al.
(författare)
-
Extra-nuclear effects of estrogen on cortical bone in males require ERαAF-1
- 2017
-
Ingår i: Journal of Molecular Endocrinology. - 0952-5041. ; 58:2, s. 105-111
-
Tidskriftsartikel (refereegranskat)abstract
- Estradiol (E2) signaling via estrogen receptor alpha (ERα) is important for the male skeleton as demonstrated by ERα inactivation in both mice and man. ERα mediates estrogenic effects not only by translocating to the nucleus and affecting gene transcription but also by extra-nuclear actions e.g., triggering cytoplasmic signaling cascades. ERα contains various domains, and the role of activation function 1 (ERαAF-1) is known to be tissue specific. The aim of this study was to determine the importance of extra-nuclear estrogen effects for the skeleton in males and to determine the role of ERαAF-1 for mediating these effects. Five-month-old male wild-type (WT) and ERαAF-1-inactivated (ERαAF-10) mice were orchidectomized and treated with equimolar doses of 17β-estradiol (E2) or an estrogen dendrimer conjugate (EDC), which is incapable of entering the nucleus and thereby only initiates extra-nuclear ER actions or their corresponding vehicles for 3.5 weeks. As expected, E2 treatment increased cortical thickness and trabecular bone volume per total volume (BV/TV) in WT males. EDC treatment increased cortical thickness in WT males, whereas no effect was detected in trabecular bone. In ERαAF-10 males, E2 treatment increased cortical thickness, but did not affect trabecular bone. Interestingly, the effect of EDC on cortical bone was abolished in ERαAF-10 mice. In conclusion, extra-nuclear estrogen signaling affects cortical bone mass in males, and this effect is dependent on a functional ERαAF-1. Increased knowledge regarding estrogen signaling mechanisms in the regulation of the male skeleton may aid the development of new treatment options for male osteoporosis.
|
|
| 22. |
- Farman, Helen H., 1983, et al.
(författare)
-
Membrane estrogen receptor alpha is essential for estrogen signaling in the male skeleton
- 2018
-
Ingår i: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 239:3, s. 303-312
-
Tidskriftsartikel (refereegranskat)abstract
- The importance of estrogen receptor alpha (ER alpha) for the regulation of bone mass in males is well established. ERa mediates estrogenic effects both via nuclear and membraneinitiated ER alpha (mER alpha) signaling. The role of mERa signaling for the effects of estrogen on bone in male mice is unknown. To investigate the role of mERa signaling, we have used mice (Nuclear-Only-ER; NOER) with a point mutation (C451A), which results in inhibited trafficking of ER alpha to the plasma membrane. Gonadal-intact male NOER mice had a significantly decreased total body areal bone mineral density (aBMD) compared to WT littermates at 3, 6 and 9 months of age as measured by dual-energy X-ray absorptiometry (DEXA). High-resolution microcomputed tomography (mu CT) analysis of tibia in 3-month-old males demonstrated a decrease in cortical and trabecular thickness in NOER mice compared to WT littermates. As expected, estradiol (E2) treatment of orchidectomized (ORX) WT mice increased total body aBMD, trabecular BV/TV and cortical thickness in tibia compared to placebo treatment. E2 treatment increased these skeletal parameters also in ORX NOER mice. However, the estrogenic responses were significantly decreased in ORX NOER mice compared with ORX WT mice. In conclusion, mER alpha is essential for normal estrogen signaling in both trabecular and cortical bone in male mice. Increased knowledge of estrogen signaling mechanisms in the regulation of the male skeleton may aid in the development of new treatment options for male osteoporosis.
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Gustafsson, Helen, et al.
(författare)
-
EPID dosimetry: Effect of different layers of materials on absorbed dose response
- 2009
-
Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 36:12, s. 5665-5674
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Commercial EPIDs are normally used in indirect detection mode (iEPID) where incident x-ray photons are converted to optical photons in a phosphor scintillator, which are then detected by a photodiode array. The EPIDs are constructed from a number of nonwater equivalent materials which affect the dose response of the detector. The so-called direct detection EPIDs (dEPIDs), operating without the phosphor layer, have been reported to display dose response close to in-water data. In this study, the effect that different layers of materials in the EPID have on the dose response was experimentally investigated and evaluated with respect to changes in field size response and beam profiles. Methods: An iEPID was disassembled and the different layers of materials were removed or replaced with other materials. Data were also obtained on and off the support arm and with a sheet of opaque paper blocking the optical photons from the gadolinium oxysulfide (Gd2S2O: Tb) phosphor layer. Field size response was measured for field sizes ranging from 2 x 2 to 25 x 25 cm(2), and profiles for the 25 x 25 cm(2) beams were extracted from the data. Results: The iEPID configuration was found to be very sensitive to backscatter. The increases in output with solid water backscatter compared to the no backscatter case were 14.7% and 6.6% at the largest field size investigated for the 6 and 18 MV beams, respectively. The Gd2S2O: Tb phosphor layer had a large influence on field size response as well as beam profiles for 6 MV photons, while no major effects were observed for the 18 MV beam. For 18 MV large differences in dose response were found when the standard 1 mm Cu buildup was changed for d(max) equivalent Cu or solid water buildup, indicating that head scatter largely influences dose response for this energy. When the optical photons originating in the Gd2S2O: Tb layer were blocked from reaching the photodiodes, both field size output data and beam profiles corresponded well with data obtained in the dEPID configuration as well as reference ion chamber data for both energies. Conclusions: As expected, changing the layers of material in the EPID had a dramatic effect on dose response, which was often quite complex. For 6 MV, the complex dose response is mainly caused by the optical photons from the Gd2S2O: Tb layer, while insufficient filtering of scattered radiation largely affects the dose response for the 18 MV beam. The iEPID was also found to be very sensitive to backscatter for both energies. Blocking the optical photons created in the Gd2S2O: Tb layer essentially changed the iEPID configuration into the dEPID configuration, thus demonstrating great potential for a system that can be optimized for both imaging and dosimetry. (C) 2009 American Association of Physicists in Medicine.
|
|
| 26. |
|
|
| 27. |
- Gustafsson, Helen, et al.
(författare)
-
MAGIC-type polymer gel for three-dimensional dosimetry: intensity-modulated radiation therapy verification.
- 2003
-
Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 30:6, s. 1264-1271
-
Tidskriftsartikel (refereegranskat)abstract
- A new type of polymer gel dosimeter, which responds well to absorbed dose even when manufactured in the presence of normal levels of oxygen, was recently described by Fong et al. [Phys. Med. Biol. 46, 3105-3113 (2001)] and referred to by the acronym MAGIC. The aim of this study was to investigate the feasibility of using this new type of gel for intensity-modulated radiation therapy (IMRT) verification. Gel manufacturing was carried out in room atmosphere under normal levels of oxygen. IMRT inverse treatment planning was performed using the Helios software. The gel was irradiated using a linear accelerator equipped with a dynamic multileaf collimator, and intensity modulation was achieved using sliding window technique. The response to absorbed dose was evaluated using magnetic resonance imaging. Measured and calculated dose distributions were compared with regard to in-plane isodoses and dose volume histograms. In addition, the spatial and dosimetric accuracy was evaluated using the gamma formalism. Good agreement between calculated and measured data was obtained. In the isocenter plane, the 70% and 90% isodoses acquired using the different methods are mostly within 2 mm, with up to 3 mm disagreement at isolated points. For the planning target volume (PTV), the calculated mean relative dose was 96.8 +/- 2.5% (1 SD) and the measured relative mean dose was 98.6 +/- 2.2%. Corresponding data for an organ at risk was 34.4 +/- 0.9% and 32.7 +/- 0.7%, respectively. The gamma criterion (3 mm spatial/3% dose deviation) was fulfilled for 94% of the pixels in the target region. Discrepancies were found in hot spots the upper and lower parts of the PTV, where the measured dose was up to 11% higher than calculated. This was attributed to sub optimal scatter kernels used in the treatment planning system dose calculations. Our results indicate great potential for IMRT verification using MAGIC-type polymer gel.
|
|
| 28. |
- Gustafsson, Helen
(författare)
-
Radiotherapy Gel Dosimetry: Development and Application of Normoxic Polymer Gels
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In many radiotherapy applications, true three-dimensional dosimetry with good spatial resolution that can be achieved in a single measurement would be of great value. Polymer gel dosimetry fulfils many of the demands on such a system. In this study, methods to facilitate the implementation of gel dosimetry have been investigated. A new type of polymer gel, for which the response to absorbed dose is not negatively affected even if manufacturing is undertaken at normal levels of oxygen, called normoxic gel, was studied. The concept of percentage dose resolution was introduced to enable optimization of gel compositions for use in relative dosimetry applications. This concept was applied to demonstrate the effects of varying the gel composition on gel performance. Comparison between data obtained using magnetic resonance imaging and FT-Raman spectroscopy indicated that not all water protons attached to the polymer are accessible for exchange of magnetization with other proton groups. Dose response characteristics were investigated for a polymer gel containing the antioxidant tetrakis(hydroxymethyl)phosphonium. The transversal relaxation time (R2) versus dose response increased with increasing amounts of monomer, while no systematic dependence on antioxidant concentration was observed. The investigated normoxic gel exhibited a dependence on temperature during irradiation, leading to differences in absolute R2 as well as deviations in relative depth dose curves. It was suggested that the deviation in R2 can be attributed to structural differences in the polymer matrix, caused by varying polymerisation temperature. A linear relationship between absorbed dose and optical attenuation coefficient was observed, which demonstrates the potential for evaluation using light transmission measurements. Low-density gel was manufactured by mixing normal density normoxic gel with Styrofoamä spheres. A linear correlation between R2 and dose was observed for doses up to 15 Gy. Possible dose response dependence on linear energy transfer (LET) was investigated using proton beam absorbed dose measurements. An increased LET with depth was closely followed by a decrease in relative detector sensitivity, indicating that the response of this type of gel detector is dependent on LET. No significant effects were observed for LET < 2.5 keV/mm, indicating that the detector response would not be altered in the range of LET values expected for photons or electrons in a clinical range of energies. The feasibility of using normoxic gel for intensity-modulated radiation therapy verification was investigated. Good agreement between treatment planning system calculations and measured data was obtained. For the planning target volume, the calculated and the measured mean relative dose was 96.8±2.5% (±1 SD) and 98.6±2.2%, respectively. The results indicated great potential for intensity-modulated radiation therapy verification using normoxic polymer gel.
|
|
| 29. |
- Gustafsson, Karin L., 1987, et al.
(författare)
-
A tissue-specific role of membrane-initiated ERα signaling for the effects of SERMs
- 2022
-
Ingår i: Journal of Endocrinology. - 0022-0795. ; 253:2, s. 75-84
-
Tidskriftsartikel (refereegranskat)abstract
- Selective estrogen receptor modulators (SERMs) act as estrogen receptor (ER) agonists or antagonists in a tissue-specific manner. ERs exert effects via nuclear actions but can also utilize membrane-initiated signaling pathways. To dete rmine if membrane-initiated ERα (mERα) signaling affects SERM action in a tissue-specific manner, C451 A mice, lacking mERα signaling due to a mutation at palmitoylation site C451, were treated with Lasofoxifene (Las), Bazedoxifene (Bza), or estradi ol (E2), and various tissues were evaluated. Las and Bza treatment increased uterine weight to a similar extent in C451A and control mice, demonstrating mERα-independent uterine SERM effects, while the E2 effect on the uterus was predominantly mER α-dependent. Las and Bza treatment increased both trabecular and cortical bone mass in controls to a similar degree as E2, while both SERM and E2 treatment effects were abse nt in C451A mice. This demonstrates that SERM effects, similar to E2 effects, in th e skeleton are mERα- dependent. Both Las and E2 treatment decreased thymus weight in controls, while neither treatment affected the thymus in C451A mice, demonstrati ng mERα-dependent SERM and E2 effects in this tissue. Interestingly, both SERM and E2 treatments decreased the total body fat percent in C451A mice, demonstrating the ability of these treatments to affect fat tissue in the absence of functional mER α signaling. In conclusion, mERα signaling can modulate SERM responses in a tissue-specific manne r. This novel knowledge increases the understanding of the mechanisms behind SERM effects and may thereby facilitate the development of new improved SERMs.
|
|
| 30. |
- Gustafsson, Karin L., 1987, et al.
(författare)
-
Arginine site 264 in murine estrogen receptor alpha is dispensable for the regulation of the skeleton.
- 2021
-
Ingår i: American journal of physiology. Endocrinology and metabolism. - 1522-1555. ; 320:1
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogen protects against bone loss, but is not a suitable treatment due to adverse effects in other tissues. Increased knowledge regarding estrogen signaling in estrogen-responsive tissues is therefore warranted to aid the development of bone-specific estrogen treatments. Estrogen receptor alpha (ERα), the main mediator of estrogenic effects in bone, is widely subjected to posttranslational modifications (PTMs). In vitro studies have shown that methylation at site R260 in the human ERα affects receptor localization and intracellular signaling. The corresponding amino acid R264 in murine ERα has been shown to have a functional role in endothelium in vivo; albeit the methylation of R264 in the murine gene is yet to be empirically demonstrated. The aim of this study was to investigate if R264 in ERα is involved in the regulation of the skeleton in vivo. DXA analysis at three, six, nine, and twelve months of age showed no differences in total body areal BMD between R264A and WT in either female or male mice. Furthermore, analyses using CT demonstrated that trabecular bone mass in tibia and vertebra, and cortical thickness in tibia, were similar between R264A and WT mice. In addition, R264A females displayed a normal estrogen treatment response in trabecular bone mass, as well as in cortical thickness. Furthermore, uterus, thymus, and adipose tissue responded similarly in R264A and WT female mice after estrogen treatment. In conclusion, our novel finding that mutation of R264 in ERα does not affect the regulation of the skeleton, together with the known role of R264 for ERα-mediated endothelial effects, supports the concept that R264 determines tissue specificity of ERα.
|
|
| 31. |
- Gustafsson, Karin L., 1987, et al.
(författare)
-
ER alpha expression in T lymphocytes is dispensable for estrogenic effects in bone
- 2018
-
Ingår i: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 238:2, s. 129-136
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogen treatment has positive effects on the skeleton, and we have shown that estrogen receptor alpha (ERa) expression in cells of hematopoietic origin contributes to a normal estrogen treatment response in bone tissue. T lymphocytes are implicated in the estrogenic regulation of bone mass, but it is not known whether T lymphocytes are direct estrogen target cells. Therefore, the aim of this study was to determine the importance of ERa expression in T lymphocytes for the estrogenic regulation of the skeleton using female mice lacking ERa expression specifically in T lymphocytes (Lck-ERa-/-) and ERaflox/flox littermate (control) mice. Deletion of ERa expression in T lymphocytes did not affect bone mineral density (BMD) in sham-operated Lck-ERa-/compared to control mice, and ovariectomy (ovx) resulted in a similar decrease in BMD in control and Lck-ERa-/- mice compared to sham-operated mice. Furthermore, estrogen treatment of ovx Lck-ERa-/- led to an increased BMD that was indistinguishable from the increase seen after estrogen treatment of ovx control mice. Detailed analysis of both the appendicular (femur) and axial (vertebrae) skeleton showed that both trabecular and cortical bone parameters responded to a similar extent regardless of the presence of ERa in T lymphocytes. In conclusion, ERa expression in T lymphocytes is dispensable for normal estrogenic regulation of bone mass in female mice.
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
- Högberg, Carl, et al.
(författare)
-
The reversible oral P2Y(12) antagonist AZD6140 inhibits ADP-induced contractions in murine and human vasculature.
- 2010
-
Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 142, s. 187-192
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The platelet ADP P2Y(12) receptor which is a target for the antithrombotic drug clopidogrel is also distributed on vascular smooth muscle cells and stimulate contraction. This study investigates whether AZD6140, in contrast to clopidogrel, can inhibit ADP-mediated arterial contractions. METHODS: Mice were treated with clopidogrel, 50 mg/kg, 24 and 2 h before experiment. Thoracic aorta ring segments from both clopidogrel-treated (n=5) and untreated (n=4) mice were mounted in myograph baths. Contractions of human left internal mammary arteries (IMA) and small arteries were studied in an identical manner. RESULTS: Clopidogrel treatment per os did not inhibit contractions by the stable ADP analogue 2-MeSADP (10 microM). However, addition of 1 microM AZD6140 in vitro inhibited ADP contraction (% of maximal contraction by 60 mM K(+)) both in the clopidogrel-treated, from 64% to 32% (P=0.002) and in the untreated group, from 59% to 33% (P=0.015). 2-MeSADP contractions in human IMA and small arteries were inhibited by AZD6140. CONCLUSIONS: The antiplatelet drug AZD6140 blocks the contractile effects of ADP in both murine and human vasculature. These effects of AZD6140 could be beneficial in the management of conditions in which vasospasm may play a role.
|
|
| 35. |
|
|
| 36. |
- Jakobsson, Martin, et al.
(författare)
-
Evidence for an ice shelf covering the central Arctic Ocean during the penultimate glaciation
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- The hypothesis of a km-thick ice shelf covering the entire Arctic Ocean during peak glacial conditions was proposed nearly half a century ago. Floating ice shelves preserve few direct traces after their disappearance, making reconstructions difficult. Seafloor imprints of ice shelves should, however, exist where ice grounded along their flow paths. Here we present new evidence of ice-shelf groundings on bathymetric highs in the central Arctic Ocean, resurrecting the concept of an ice shelf extending over the entire central Arctic Ocean during at least one previous ice age. New and previously mapped glacial landforms together reveal flow of a spatially coherent, in some regions41-km thick, central Arctic Ocean ice shelf dated to marine isotope stage 6 (similar to 140 ka). Bathymetric highs were likely critical in the ice-shelf development by acting as pinning points where stabilizing ice rises formed, thereby providing sufficient back stress to allow ice shelf thickening.
|
|
| 37. |
- Justice, Anne E., et al.
(författare)
-
Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
-
Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
|
|
| 38. |
- Järlskog, Ida, 1991, et al.
(författare)
-
Occurrence of tire and bitumen wear microplastics on urban streets and in sweepsand and washwater
- 2020
-
Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 729
-
Tidskriftsartikel (refereegranskat)abstract
- Tire and road wear particles have been identified as a potential major source of microplastics in the environment. However, more knowledge of the emissions and their further fate in the environment is needed, and the effectiveness and benefits of potential measures must be investigated to support future risk management efforts. Here the concentrations of tire and bitumen microplastic particles (TBMP) on roads and in nearby in stormwater, sweepsand and washwater were measured for the first time within the same area and time period. The analysis also included plastic, paint and fiber particles. Road dust was sampled on the road surface using a wet dust sampler, before and after street sweeping on two occasions. On each of these occasions, and several occasions during a four-month period with frequent street sweeping, sweepsand and washwater, as well as flow-weighted sampling of stormwater, were collected. TBMP concentrations were operationally defined, using density separation for some samples, followed by analysis by stereo microscopy. Sodium iodide (NaI) was found to be effective for density separation of TBMP. The largest proportion of anthropogenic microplastics detected consisted of tire tread wear and bitumen. The number of TBMP ≥100 μm in the WDS samples was up to 2561 particles/L. Sweepsand and washwater contained high amounts of TBMP ≥100 μm, up to 2170 particles/kg dw and 4500 particles/L, respectively. The results show that the sweeper collects considerable amounts of TBMP, and thus weekly sweeping might prevent further transport of TBMP to the receiving stormwater. In stormwater the number of particles ≥100 μm was up to 3 particles/L and ≥ 20 μm was up to 5900 particles/L showing the importance of analysing smaller microparticle sizes than 100 μm in all samples in future studies. This study also confirms that there is a substantial volume of TBMP generated from traffic that enters the environment.
|
|
| 39. |
- Järlskog, Ida, 1991, et al.
(författare)
-
Traffic-related microplastic particles, metals, and organic pollutants in an urban area under reconstruction
- 2021
-
Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 774
-
Tidskriftsartikel (refereegranskat)abstract
- In urban environments, particularly areas under reconstruction, metals, organic pollutants (OP), and microplastics (MP), are released in large amounts due to heavy traffic. Road runoff, a major transport route for urban pollutants, contributes significantly to a deteriorated water quality in receiving waters. This study was conducted in Gothenburg, Sweden, and is unique because it simultaneously investigates the occurrence of OP, metals, and MP on roads and in stormwater from an urban area under reconstruction. Correlations between the various pollutants were also explored. The study was carried out by collecting washwater and sweepsand generated from street sweeping, road surface sampling, and flow-proportional stormwater sampling on several occasions. The liquid and solid samples were analyzed for metals, polycyclic aromatic hydrocarbons (PAH), oxy-PAH, aliphatics, aromatics, phthalates, and MP. The occurrence of OP was also analyzed with a non-target screening method of selected samples. Microplastics, i.e. plastic fragments/fibers, paint fragments, tire wear particles (TWP) and bitumen, were analyzed with a method based on density separation with sodium iodide and identification with a stereo microscope, melt-tests, and tactile identification. MP concentrations amounted to 1500 particles/L in stormwater, 51,000 particles/L in washwater, and 2.6 × 106 particles/kg dw in sweepsand. In stormwater, washwater and sweepsand, MP ≥20 μm were found to be dominated by TWP (38%, 83% and 78%, respectively). The results confirm traffic as an important source to MP, OP, and metal emissions. Concentrations exceeding water and sediment quality guidelines for metals (e.g. Cu and Zn), PAH, phthalates, and aliphatic hydrocarbons in the C16–C35 fraction were found in most samples. The results show that the street sweeper collects large amounts of polluted materials and thereby prevents further spread of the pollutants to the receiving stormwater.
|
|
| 40. |
- Kanoni, Stavroula, et al.
(författare)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
|
|
| 41. |
- Karlsson, Anna, et al.
(författare)
-
Dose integration characteristics in normoxic polymer gel dosimetry investigated using sequential beam irradiation
- 2007
-
Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 52:15, s. 4697-4706
-
Tidskriftsartikel (refereegranskat)abstract
- Dose integration properties were investigated for normoxic polymer gels based on methacrylic acid (nMAG) and acrylamide/ N, N'-methylenebisacrylamide (nPAG). The effect of sequential irradiation was studied for different fractionation schemes and varying amounts of methacrylic acid for the nMAG gels. Magnetic resonance imaging (MRI) was used for read out of the absorbed dose response. The investigated gels exhibited a dependence on the fractionation scheme. The response when the total dose was divided into fractions of 0.5 Gy was compared with the response when the total dose was delivered in a single fraction. The slope of the R2 versus the absorbed dose response decreased when the absorbed dose per fraction was increased. Also, for higher amounts of methacrylic acid in the nMAG system the difference in the response increased. For gels containing 2, 4, 6 and 8% methacrylic acid, the R2 versus the absorbed dose response increased by 35, 37, 63 and 93%, respectively. Furthermore, the effect of the fractionation was larger when a higher total absorbed dose was given. The effect was less pronounced for the investigated nPAG, containing 3% acrylamide and 3% N, N'-methylenebisacrylamide, than for the nMAG systems. Consequently, this study indicates that the nPAG system has preferable beam integration characteristics compared with the nMAG system.
|
|
| 42. |
- Karlsson, Helen, et al.
(författare)
-
Wear Particles from Studded Tires and Granite Pavement Induce Pro-inflammatory Alterations in Human Monocyte-Derived Macrophages : A Proteomic Study.
- 2011
-
Ingår i: Chemical Research in Toxicology. - : American Chemical Society. - 0893-228X .- 1520-5010. ; 24, s. 45-53
-
Tidskriftsartikel (refereegranskat)abstract
- Airborne particulate matter is considered to be one of the environmental contributors to the mortality in cancer, respiratory, and cardiovascular diseases. For future preventive actions, it is of major concern to investigate the toxicity of defined groups of airborne particles and to clarify their pathways in biological tissues. To expand the knowledge beyond general inflammatory markers, this study examined the toxicoproteomic effects on human monocyte derived macrophages after exposure to wear particles generated from the interface of studded tires and a granite-containing pavement. As comparison, the effect of endotoxin was also investigated. The macrophage proteome was separated using two-dimensional gel electrophoresis. Detected proteins were quantified, and selected proteins were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry. Among analyzed proteins, seven were significantly decreased and three were increased by exposure to wear particles as compared to unexposed control cells. Endotoxin exposure resulted in significant changes in the expression of six proteins: four decreased and two increased. For example, macrophage capping protein was significantly increased after wear particle exposure only, whereas calgizzarin and galectin-3 were increased by both wear particle and endotoxin exposure. Overall, proteins associated with inflammatory response were increased and proteins involved in cellular functions such as redox balance, anti-inflammatory response, and glycolysis were decreased. Investigating the effects of characterized wear particles on human macrophages with a toxicoproteomic approach has shown to be useful in the search for more detailed information about specific pathways and possible biological markers.
|
|
| 43. |
|
|
| 44. |
- Lagerquist, Marie K, et al.
(författare)
-
Acute fat loss does not affect bone mass
- 2021
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity has previously been thought to protect bone since high body weight and body mass index are associated with high bone mass. However, some more recent studies suggest that increased adiposity negatively impacts bone mass. Here, we aimed to test whether acute loss of adipose tissue, via adipocyte apoptosis, alters bone mass in age-related obese mice. Adipocyte apoptosis was induced in obese male FAT-ATTAC mice through AP20187 dimerizer-mediated activation of caspase 8 selectively in adipocytes. In a short-term experiment, dimerizer was administered to 5.5 month-old mice that were terminated 2 weeks later. At termination, the total fat mass weighed 58% less in dimerizer-treated mice compared with vehicle-treated controls, but bone mass did not differ. To allow for the detection of long-term effects, we used 9-month-old mice that were terminated six weeks after dimerizer administration. In this experiment, the total fat mass weighed less (- 68%) in the dimerizer-treated mice than in the controls, yet neither bone mass nor biomechanical properties differed between groups. Our findings show that adipose tissue loss, despite the reduced mechanical loading, does not affect bone in age-related obese mice. Future studies are needed to test whether adipose tissue loss is beneficial during more severe obesity.
|
|
| 45. |
- Larsson, Jenny, 1974-, et al.
(författare)
-
Anti-inflammatory effects of a titanium-peroxy gel: role of oxygen metabolites and apoptosis.
- 2004
-
Ingår i: Journal of biomedical materials research. Part A. - : Wiley. - 1549-3296 .- 0021-9304 .- 1097-4636. ; 68:3, s. 448-57
-
Tidskriftsartikel (refereegranskat)abstract
- Polymorphonuclear neutrophils (PMN) are among the first inflammatory cells to arrive at an implant interface, where they encounter with the foreign material and may produce reactive oxygen species (ROS). During the interaction between titanium and ROS, titanium-peroxy (Ti-peroxy) compounds may be formed. We used a Ti-peroxy gel, made from titanium and hydrogen peroxide, to study the effects of Ti-peroxy compounds on PMN. In the absence of serum, the Ti-peroxy gel decreased the oxidative response of PMN to yeast and PMA and reduced PMN apoptosis without inducing necrosis. These effects could not be ascribed to the release of hydrogen peroxide from the Ti-peroxy gel, because a steady-state hydrogen peroxide producing system failed to mimic the effects of the gel. The effects were similarly unaffected when PMN were preincubated with beta(2)-integrin antibodies, questioning the involvement of adhesion molecules. Nevertheless, when a filter was used to separate the Ti-peroxy gel from the cells, the gel effect on PMN life span was abolished, pointing to a contact-dependent mechanism. In the presence of serum, the Ti-peroxy gel had no effect on the PMN oxidative response and life span, but appeared rather inert. In summary, this study demonstrates that the Ti-peroxy gel has potentially anti-inflammatory properties through a combined peroxide and physical contact effect, supporting the notion that interactions between titanium and inflammatory cells are responsible for the good performance of titanium in vivo.
|
|
| 46. |
- Larsson, Jenny, 1974-, et al.
(författare)
-
Involvement of the ß2-integrin CD18 in apoptosis signal transduction in human neutrophils
- 2000
-
Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1023-3830 .- 1420-908X. ; 49:9, s. 452-459
-
Tidskriftsartikel (refereegranskat)abstract
- Objective and design: To examine the hypothesis that an accelerated rate of neutrophil apoptosis occurs following β2-integrin activation, and further investigate the signal transduction pathways involved.Material: Human polymorphonuclear neutrophils.Treatment: Neutrophils were challenged with pansorbins coated with antibodies towards the β2-integrin subunit CD18 in a proportion of 1:100 with or without the inhibitors diphenylene iodonium (10 M), cytochalasin B (5 μg/ml), genistein (10 nM), herbimycin A (10 M) and Z-VAD-FMK (10 μM).Methods: Measurement of phosphatidylserine exposure and DNA fragmentation in flow cytometry and assessment of H2O2-production through spectrofluorometry. The results were analysed using Mann Whitney U test and Kruskal Wallis.Results: Pansorbins coated with antibodies to CD18 induce apoptosis in neutrophils (p < 0.01), and activate the production of reactive oxygen species (p < 0.01). Pre-treatment with the inhibitors have no effect on anti-CD18 induced apoptosis.Conclusion: Anti-CD18 pansorbins induce apoptosis in neutrophils through an alternative pathway not involving reactive oxygen species and independent of tyrosine phosphorylation, cytoskeletal reorganisation and caspases.
|
|
| 47. |
- Larsson, Jenny, et al.
(författare)
-
Platelet-mediated inhibition of polymorphonuclear neutrophil apoptosis principally involves membranes structures : role of sialyl-Lewisχ epitopes and CD18
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective and design: To clarify the long-time effects of platelets on polymorphonuclear neutrophils (PMNs) apoptosis, with particular emphasis on the involvement of cell adhesion molecules (CAMs).Material: Isolated human platelets and PMNs.Treatment: PMNs were treated with antibodies towards adhesion molecules CD18 (2 µg/ml), sialyl-Lewisχ (2 µg/ml) or P-selectin glycoprotein ligand 1 (5 µg/ml) and then incubated in the absence or presence of resting, thrombin-activated or inhibited platelets (PMN:platelet ratio of 1:50), platelet membrane (0.7 mg/ml; equivalent to the 1:50 ratio), or supematant from thrombin-activated platelets.Methods: Measurement of DNA fragmentation using flow cytometry, microscopical evaluation of adhesion and cell death. Light transmission analysis for recording platelet aggregation.Results: Activated, and to lesser extent, resting platelets prevented spontaneous PMN apoptosis. Comparable effects were detected by using platelet membrane. Platelet-mediated suppression of PMN apoptosis and PMN-platelet adhesion were reversed by pretreatment with antibodies directed towards the adhesive structures sialyl-Lewisχ (p<0.001).Conclusions: Our results point to a central role of CAMs in plateletinduced inhibition of PMN apoptosis. Furthermore, the results add new evidences for a close association between the hemostatic and the inflammatory systems.
|
|
| 48. |
- Lindmark, Maria, et al.
(författare)
-
Lipophosphoglycan (LPG) from Leishmania donovani inhibits phagosomal maturation and oxygen redical production in human neutrophils
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lipophosphoglycan (LPG) is the major surface glycoconjugate on Leishmania donovani promastigotes. LPG inhibits phagosome maturation and is crucial for parasite survival in macrophages. Fusion of vesicles with the phagosome is essential for the formation of a mature phagolysosorne and depolymerization of periphagosomal F-actin is likely a prerequisite for vesicle fusion. In macrophages LPG induces an accumulation of periphagosomal F-actin which is correlated to inhibition of vesicle fusion to the phagosome. In this work we investigated the effects of LPG on phagosome maturation in human neutrophils. We found that ingestion of serum-opsonised, LPG-coated yeast particles induced increased levels of periphagosomal Factin in neutrophils. Phagosome maturation was studied using antibodies to CD63 (azurophil granules), synaptotagmin II (specific granules) and LAMP-1 (specific granules, secretory vesicles, multivesicular bodies/multilaminar compartments). Results showed impaired translocation of all these three markers to phagosomes containing LPG-coated prey. The translocation of the early endosome marker Rab5A to the phagosome was not affected by LPG. The late endosomal marker Rab7 was not found in human neutrophils. Chemiluminescence studies revealed that serum-opsonised, LPG-coated yeast induced less production of reactive oxygen metabolites (ROM) compared to controls and that the production was mainly intracellular.
|
|
| 49. |
- Locke, Adam E, et al.
(författare)
-
Genetic studies of body mass index yield new insights for obesity biology.
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
|
|
| 50. |
|
|
