| 1. |
- Jansen, Willemijn J, et al.
(author)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Journal article (peer-reviewed)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 2. |
- Ekblad, Alf, 1957-, et al.
(author)
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The production and turnover of extramatrical mycelium of ectomycorrhizal fungi in forest soils : role in carbon cycling
- 2013
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In: Plant and Soil. - : Springer Science and Business Media LLC. - 0032-079X .- 1573-5036. ; 366:1-2, s. 1-27
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Research review (peer-reviewed)abstract
- There is growing evidence of the importance of extramatrical mycelium (EMM) of mycorrhizal fungi in carbon (C) cycling in ecosystems. However, our understanding has until recently been mainly based on laboratory experiments, and knowledge of such basic parameters as variations in mycelial production, standing biomass and turnover as well as the regulatory mechanisms behind such variations in forest soils is limited. Presently, the production of EMM by ectomycorrhizal (EM) fungi has been estimated at similar to 140 different forest sites to be up to several hundreds of kg per ha per year, but the published data are biased towards Picea abies in Scandinavia. Little is known about the standing biomass and turnover of EMM in other systems, and its influence on the C stored or lost from soils. Here, focussing on ectomycorrhizas, we discuss the factors that regulate the production and turnover of EMM and its role in soil C dynamics, identifying important gaps in this knowledge. C availability seems to be the key factor determining EMM production and possibly its standing biomass in forests but direct effects of mineral nutrient availability on the EMM can be important. There is great uncertainty about the rate of turnover of EMM. There is increasing evidence that residues of EM fungi play a major role in the formation of stable N and C in SOM, which highlights the need to include mycorrhizal effects in models of global soil C stores.
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| 3. |
- Lindgaard, S. C., et al.
(author)
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Hepatic arterial therapy with oxaliplatin and systemic capecitabine for patients with liver metastases from breast cancer
- 2019
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In: Breast. - : Elsevier BV. - 0960-9776. ; 43, s. 113-119
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Journal article (peer-reviewed)abstract
- Objectives: Hepatic arterial treatment (HAT) for liver metastases in patients with metastatic breast cancer (MBC) has only been investigated in few studies. Materials and methods: Two phase II trials were initiated simultaneously to evaluate capecitabine in combination with oxaliplatin in patients with MBC and liver metastases. These two trials are reported together. Continuous capecitabine (1300 mg/m2) was combined with oxaliplatin (85 mg/m2) alternating between systemic treatment and HAT followed by degradable starch microspheres with EmboCept® S every second week. Four patients participated in a pharmacokinetic analysis of oxaliplatin. Each patient had samples taken when receiving oxaliplatin systemically and as HAT with and without EmboCept® S. Results: Totally, 52 patients received HAT: 14 with liver metastases only and 38 patients with additional limited metastatic disease. The patients had previously received a median of 2 (range 0–6) chemotherapeutic regimens for MBC. The response rate was 42.3% (95% confidence interval (CI) 28.7–56.8%) with 7.7% complete and 34.6% partial responses. Median progression free survival was 10.8 months (95% CI 6.9–14.7 months) and median overall survival 27.6 months (95% CI 20.4–34.8 months). The toxicity was moderate with hand-foot syndrome (15.4%), neuropathy (9.6%), fatigue (9.6%), and abdominal pain (9.6%) being the most common grade 3 adverse events. There was no clear difference between systemic blood concentrations of oxaliplatin when given systemic or as HAT. Conclusion: HAT oxaliplatin in combination with capecitabine is safe and efficient in patients with MBC. The results are promising with high response rates and a long median progression free and overall survival.
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| 4. |
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| 5. |
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| 6. |
- Abomaray, F, et al.
(author)
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The Effect of Mesenchymal Stromal Cells Derived From Endometriotic Lesions on Natural Killer Cell Function
- 2021
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In: Frontiers in cell and developmental biology. - : Frontiers Media SA. - 2296-634X. ; 9, s. 612714-
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Journal article (peer-reviewed)abstract
- Endometriosis is an inflammatory disease that presents with ectopic endometriotic lesions. Reduced immunosurveillance of these lesions has been proposed to be playing a role in the pathology of endometriosis. Mesenchymal stromal cells (MSC) are found in ectopic lesions and may decrease immunosurveillance. In the present study, we examined if MSC contribute to reduced immunosurveillance through their immunosuppressive effects on natural killer (NK) cells. Stromal cells from endometriotic ovarian cysts (ESCcyst) and eutopic endometrium (ESCendo) of women with endometriosis and their conditioned medium were used in co-cultures with allogeneic peripheral blood NK cells. Following culture, NK cells were examined phenotypically for their expression of activating, inhibitory, maturation, and adhesion receptors and co-receptors, as well as the degranulation (CD107a) marker and the immunostimulatory (interferon-γ) and immunosuppressive (transforming growth factor beta 1 and interleukin-10) cytokines. Moreover, NK cell cytotoxicity was examined using chromium 51 release killing assays. There were no differences between ESCcyst and ESCendo regarding their effects on NK cell cytotoxicity in both conditioned medium and direct co-culture experiments. Additionally, there were no differences between ESCcyst and ESCendo regarding their impact on NK cells’ phenotype and degranulation in both conditioned medium and direct co-culture experiments. Although there were no differences found for DNAX accessory molecule-1 (DNAM-1) and NKp44, we found that the expression of the NK cell ligand CD155 that binds DNAM-1 and proliferating cell nuclear antigen (PCNA) that binds NKp44 was significantly less on ESCcyst than on ESCendo. These findings were not supported by the results that the expression of the known and unknown ligands on ESCcyst for DNAM-1 and NKp44 using chimeric proteins was not significantly different compared to ESCendo. In conclusion, the results suggest that ectopic MSC may not contribute to reduced immunosurveillance in endometriosis through their inhibitory effects on NK cells. This suggests that NK cell inhibition in the pelvic cavity of women with endometriosis develops due to other factors.
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| 7. |
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| 8. |
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| 9. |
- Aldred, Nick, et al.
(author)
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In situ study of surface exploration by barnacle cyprids (Semibalanus balanoides) using imaging surface plasmon resonance
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Other publication (other academic/artistic)abstract
- Imaging surface plasmon resonance (iSPR) was employed to investigate the interfacial adhesion phenomena that occur during the exploration of immersed surfaces by barnacle cyprids (Semibalanus balanoides). It was hypothesised that since the footprint material used by cyprids for temporary adhesion has previously been related to a large cuticular glycoprotein (SIPC), the passive deposition of cyprid footprints and the binding of SIPC to surfaces might correlate. Increased surface exploration (and footprint deposition) has also been related to increased likelihood of settlement in barnacle cyprids. If a correlation between footprint deposition and SIPC binding were to exist, therefore, there would be potential for the development of a high‐throughput assay to determine the efficacy of putative antifouling chemistries against cyprids prior to, or instead of, lengthy bio‐assays. Footprints were deposited in large numbers on carboxyl‐terminated self‐assembled monolayers (SAMs) and in very small numbers on ethylene glycol‐containing SAMs and hydrogel coatings. SIPC binding also followed the same trend. An exception to the correlation was an amineterminated SAM that accumulated few cyprid footprints, but bound SIPC strongly. It is concluded that there is great potential for the iSPR technique to be used in the evaluation of putatively non‐fouling surfaces as well as improving our understanding of the nature of the cyprid footprint material and its interactions with surfaces of different chemistry. However, the use of SIPC binding as a predictor of footprint accumulation/likelihood of settlement of cyprids to surfaces would be premature at this stage without first understanding the exceptions highlighted in this study.
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| 10. |
- Andersson, C David, et al.
(author)
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Discovery of Ligands for ADP-Ribosyltransferases via Docking-Based Virtual Screening
- 2012
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:17, s. 7706-7718
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Journal article (peer-reviewed)abstract
- The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyses the transfer of ADP-ribose units onto substrate proteins, using nicotinamide adenine dinucleotide (NAD(+)) as a co-substrate. They have a documented role in chromatin remodelling and DNA repair; and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The detailed function of most other ARTDs is still unknown. Using virtual screening we identified small ligands of ARTD7 (PARP15/BAL3) and ARTD8 (PARP14/BAL2). Thermal-shift assays confirmed that 16 compounds, belonging to eight structural classes, bound to ARTD7/ARTD8. Affinity measurements with isothermal titration calorimetry for two isomers of the most promising hit compound confirmed binding in the low micromolar range to ARTD8. Crystal structures showed anchoring of the hits in the nicotinamide pocket. These results form a starting point in the development of chemical tools for the study of the role and function of ARTD7 and ARTD8.
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| 11. |
- Björk, Robert G., 1974, et al.
(author)
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Climate-related soil changes in tundra ecosystems at Latnjajaure, northern Sweden – an ITEX-IPY project
- 2010
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In: International Polar Year Oslo Science Conference.
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Conference paper (peer-reviewed)abstract
- During the 90'ies, the International Tundra Experiment (ITEX) was established as a leading project in arctic and alpine ecology, and has become a model for many later network establishments. The present study capitalizes on the early efforts of ITEX and aims at assessing ecosystem changes in the alpine areas of northern Sweden above timberline, i.e. the tundra, in relation to global change. By using the "old" ITEX plots established during the early years of the program we have measured ecosystem respiration (ER), the Normalized Difference Vegetation Index, and nitrogen (N) mineralization over the growing season. In addition, have soil samples been taken to quantify changes in the carbon (C) and N pool, including 13C and 15N. After 12 to 15 years of open top chamber (OTC) treatment no statistical effect was found on the soil temperature (10 cm soil depth), although the was an overall increase in all OTC by +0.2°C. However, the soil moisture decreased significantly by 3-14%, depending on plant community, in the OTCs compared to ambient conditions. Preliminary, there was a 20-37% non-significant higher mean ER in the OTC compared to the ambient plots over the growing season. Furthermore, the OTC treatment did not affect the growing season mineralization of inorganic N, or total C and N content of the soil. The stable isotope data showed both enrichment and depletion as a consequence of the OTC treatment, but no general pattern was discerned. Thus, this non-significant higher ER is most likely of plant origin than soil, as the plant standing biomass has increased in the OTCs. This study does not support the current consensus that tundra soils will alter their C and N dynamics in response to climate change.
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| 12. |
- Björk, Robert G., 1974, et al.
(author)
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Long-term warming effects on carbon and nitrogen dynamics in tundra soils
- 2012
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In: 20th Anniversary ITEX Workshop, El Paso, USA, 17–21 January 2012.
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Conference paper (other academic/artistic)abstract
- During IPY 2008 we used the ITEX experiment in Latnjajaure (northern Sweden), established during the early years of the program, to investigate long-term warming effects on ecosystem respiration (ER), carbon (C) and nitrogen (N) pool (including d13C and d15N), soil organic C (SOC) chemical composition, and N mineralization among plant communities. After 12 to 15 years of open top chamber (OTC) treatment no statistical effect was found on the soil temperature (10 cm soil depth), although the was an overall increase in all OTC by +0.2°C. However, the soil moisture decreased significantly by 3-14%, depending on plant community, in the OTCs compared to ambient conditions. Preliminary, there was a 19-61% non-significant increase in annual growing season ER in the OTC compared to the ambient plots over the growing season. The were distinct differences in the SOM functional composition among plant communities with c 10% more O-alkyls stored in tussock tundra than in dry meadow. The OTCs did not consistently alter the SOM composition among the vegetation types but clearly showed a trend for reduced aliphatic and O-alkyl C in the OTCs suggesting increased decomposition (or reduced inputs) of these compounds. Thus, the non-significantly higher ER may in some communities be of plant origin linked to greater plant biomass in the OTCs, and in other (e.g. tussock tundra) from increased decomposition rates. In conclusion, this study showed that 12-15 years of OTC treatment had a modest effects impact C and N dynamics in tundra soils specific to distinct plant communities.
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| 13. |
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| 14. |
- Dereke, J., et al.
(author)
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Structural and immunoendocrine remodeling in gut, pancreas and thymus in weaning rats fed powdered milk diets rich in Maillard reactants
- 2022
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12
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Journal article (peer-reviewed)abstract
- Western diet is extending worldwide and suspected to be associated with various metabolic diseases. Many food products have skim milk powder added to it and, during processing, lactose reacts with milk proteins and Maillard reaction products (MRPs) are formed. Dietary MRPs are suggested risk factors for metabolic dysregulation, but the mechanisms behind are still enigmatic. Here we describe that weaning rats fed diets rich in MRPs are affected in both their immune and endocrine systems. Marked structural changes in pancreas, intestine and thymus are noted already after 1 week of exposure. The pancreatic islets become sparser, the intestinal mucosa is thinner, and thymus displays increased apoptosis and atrophy. Glucagon- like peptide-1 (GLP-1) seems to play a key role in that the number of GLP-1 expressing cells is up-regulated in endocrine pancreas but down-regulated in the intestinal mucosa. Further, intestinal GLP-1-immunoreactive cells are juxta positioned not only to nerve fibres and tuft cells, as previously described, but also to intraepithelial CD3 positive T cells, rendering them a strategic location in metabolic regulation. Our results suggest dietary MRPs to cause metabolic disorders, dysregulation of intestinal GLP-1- immunoreactive cells, arrest in pancreas development and thymus atrophy.
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| 15. |
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| 16. |
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| 17. |
- Ekblad, A, et al.
(author)
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Soft Tissue Repair with Easy-Accessible Autologous Newborn Placenta or Umbilical Cord Blood in Severe Malformations: A Primary Evaluation
- 2017
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In: Stem cells international. - : Hindawi Limited. - 1687-966X .- 1687-9678. ; 2017, s. 1626741-
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Journal article (peer-reviewed)abstract
- Disrupted organogenesis leads to permanent malformations that may require surgical correction. Autologous tissue grafts may be needed in severe lack of orthotopic tissue but include donor site morbidity. The placenta is commonly discarded after birth and has a therapeutic potential. The aim of this study was to determine if the amnion from placenta or plasma rich of growth factors (PRGF) with mononuclear cells (MNC) from umbilical cord blood (UCB), collected noninvasively, could be used as bio-constructs for autologous transplantation as an easy-accessible no cell culture-required method. Human amnion and PRGF gel were isolated and kept in culture for up to 21 days with or without small intestine submucosa (SIS). The cells in the constructs showed a robust phenotype without induced increased proliferation (Ki67) or apoptosis (caspase 3), but the constructs showed decreased integrity of the amnion-epithelial layer at the end of culture. Amnion-residing cells in the SIS constructs expressed CD73 or pan-cytokeratin, and cells in the PRGF-SIS constructs expressed CD45 and CD34. This study shows that amnion and UCB are potential sources for production of autologous grafts in the correction of congenital soft tissue defects. The constructs can be made promptly after birth with minimal handling or cell expansion needed.
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| 18. |
- Ekblad, C., et al.
(author)
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Enzymatic-mechanical pulping of bast fibers from flax and hemp
- 2005
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In: Cellulose Chemistry and Technology. - 0576-9787. ; 39:02-jan, s. 95-103
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Journal article (peer-reviewed)abstract
- A technique for pulping of bast fibers of flax (Linum usitatissimum) and hemp (Cannabis sativa), based on treatment with cellulolytic and pectinolytic enzymes has been developed. Initially the bast fibers were mechanically separated from shieves and subjected to washing with diluted acid, followed by enzyme treatment, an alkaline hydrogen peroxide bleaching step that also inactivated the enzymes, and finally beating in a laboratory beater. Brightness, dewatering and strength of handsheets were comparable with the traditionally-made pulps. Fibers not treated with enzymes could not be beaten. The main pulping effect is related to cellulases, but the presence of pectinases influenced both brightness and strength properties.
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| 19. |
- Ekblad, Eva, et al.
(author)
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Innervation of the small intestine.
- 2002
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In: Biology of the Intestine in Growing Animals. - 9780444509284 - 0444509283 ; , s. 235-235
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Book chapter (other academic/artistic)abstract
- Intestinal activities are controlled and co-ordinated by way of neuronal reflexes involving both extrinsic and intramural neurones, the enteric nervous system (ENS). This review focuses on the organisation, development and functional properties of the intestinal innervation and of the neurotransmitters utilised.
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| 20. |
- Ekblad, S, et al.
(author)
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Help for refugees
- 1997
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In: World health forum. - 0251-2432. ; 18:3-4, s. 305-310
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Journal article (peer-reviewed)
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| 21. |
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| 22. |
- Ekblad, Torun, et al.
(author)
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Towards small molecule inhibitors of mono-ADP-ribosyltransferases
- 2015
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In: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 95, s. 546-551
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Journal article (peer-reviewed)abstract
- Protein ADP-ribosylation is a post-translational modification involved in DNA repair, protein degradation, transcription regulation, and epigenetic events. Intracellular ADP-ribosylation is catalyzed predominantly by ADP-ribosyltransferases with diphtheria toxin homology (ARTDs). The most prominent member of the ARTD family, poly(ADP-ribose) polymerase-1 (ARTD1/PARP1) has been a target for cancer drug development for decades. Current PARP inhibitors are generally non-selective, and inhibit the mono-ADP-ribosyltransferases with low potency. Here we describe the synthesis of acylated amino benzamides and screening against the mono-ADP-ribosyltransferases ARTD7/PARP15, ARTD8/PARP14, ARTD10/PARP10, and the poly-ADP-ribosyltransferase ARTD1/PARP1. The most potent compound inhibits ARTD10 with sub-micromolar IC50.
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| 23. |
- Garofalo, Fabio, et al.
(author)
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Statistic estimation of cell compressibility based on acoustophoretic separation data
- 2020
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In: Microfluidics and Nanofluidics. - : Springer Science and Business Media LLC. - 1613-4982 .- 1613-4990. ; 24:8
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Journal article (peer-reviewed)abstract
- We present a new experimental method that measures the compressibility of phenotype-specific cell populations. This is done by performing statistical analysis of the cell counts from the outlets of an acoustophoresis chip as a function of the increasing actuator voltage (i.e. acoustic energy density) during acoustophoretic separation. The theoretical separation performance curve, henceforth, Side-Stream Recovery (SSR), vs the piezo-actuator voltage (V) is derived by moment analysis of a one-dimensional model of acoustophoresis separation, accounting for distributions of the cell or microparticle properties and the system parameters (hydrodynamics, radiation force, drag enhancement, and acoustic streaming). The acoustophoretic device is calibrated with polymer microbeads of known properties by fitting the experimental SSR with the theoretical SSR , in which the acoustic energy density is considered proportional to the squared voltage, i.e. Eac=αV2. The fitting parameter α for the calibration procedure is the device effectivity, reflecting the efficiency in performing acoustophoretic microparticle displacement. Once calibrated, the compressibility of unknown cells is estimated by fitting experimental SSR cell data points with the theoretical SSR curve. In this procedure, the microparticle compressibility is the fitting parameter. The method is applied to estimate the compressibility of a variety of cell populations showing its utility in terms of rapid analysis and need for minute sample amounts.
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| 24. |
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| 25. |
- Kannisto, P, et al.
(author)
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Existence and coexistence of peptides in nerves of the mammalian ovary and oviduct demonstrated by immunocytochemistry
- 1986
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In: Histochemistry. - : Springer Science and Business Media LLC. - 0301-5564 .- 1432-119X. ; 86:1, s. 25-34
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Journal article (peer-reviewed)abstract
- The immunocytochemical distribution of substance P (SP), gastrin releasing peptide (GRP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), and neuropeptide Y (NPY) was studied in the ovary and the Fallopian tube (oviduct) of rats, guinea-pigs, cows, pigs and humans. Generally, the nerve supply was better developed in the oviduct than in the ovary. GRP fibers were most scarce in all tissues. Nerves containing SP were particularly numerous in the oviduct of rat and guinea-pig, supplying the muscular wall and blood vessels. VIP and PHI coexisted in dense plexuses of nerves, not only around blood vessels but also in the follicular wall and the interstitial gland of the ovary, as well as within the smooth muscle layers and subepithelially in the oviduct. The general distribution of NPY was similar, but these immunoreactive nerves were even more numerous. Sequential staining for dopamine-beta-hydroxylase and NPY together with results of chemical sympathectomy with 6-hydroxydopamine suggested that NPY was stored in the noradrenergic sympathetic nerves.
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| 26. |
- Ladd, Brenton, et al.
(author)
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Carbon isotopic signatures of soil organic matter correlate with leaf area index across woody biomes
- 2014
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In: Journal of Ecology. - : Wiley. - 0022-0477 .- 1365-2745. ; 102:6, s. 1606-1611
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Journal article (peer-reviewed)abstract
- Leaf area index (LAI), a measure of canopy density, is a key variable for modelling and understanding primary productivity, and also water use and energy exchange in forest ecosystems. However, LAI varies considerably with phenology and disturbance patterns, so alternative approaches to quantifying stand-level processes should be considered. The carbon isotope composition of soil organic matter (C-13(SOM)) provides a time-integrated, productivity-weighted measure of physiological and stand-level processes, reflecting biomass deposition from seasonal to decadal time scales.Our primary aim was to explore how well LAI correlates with C-13(SOM) across biomes.Using a global data set spanning large environmental gradients in tropical, temperate and boreal forest and woodland, we assess the strength of the correlation between LAI and C-13(SOM); we also assess climatic variables derived from the WorldClim database.We found that LAI was strongly correlated with C-13(SOM), but was also correlated with Mean Temperature of the Wettest Quarter, Mean Precipitation of Warmest Quarter and Annual Solar Radiation across and within biomes.Synthesis. Our results demonstrate that C-13(SOM) values can provide spatially explicit estimates of leaf area index (LAI) and could therefore serve as a surrogate for productivity and water use. While C-13(SOM) has traditionally been used to reconstruct the relative abundance of C-3 versus C-4 species, the results of this study demonstrate that within stable C-3- or C-4-dominated biomes, C-13(SOM) can provide additional insights. The fact that LAI is strongly correlated to C-13(SOM) may allow for a more nuanced interpretation of ecosystem properties of palaeoecosystems based on palaeosol C-13 values.
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| 27. |
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| 28. |
- Lin, CH, et al.
(author)
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Human ex vivo spinal cord slice culture as a useful model of neural development, lesion, and allogeneic neural cell therapy
- 2020
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In: Stem cell research & therapy. - : Springer Science and Business Media LLC. - 1757-6512. ; 11:1, s. 320-
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Journal article (peer-reviewed)abstract
- BackgroundThere are multiple promising treatment strategies for central nervous system trauma and disease. However, to develop clinically potent and safe treatments, models of human-specific conditions are needed to complement in vitro and in vivo animal model-based studies.MethodsWe established human brain stem and spinal cord (cross- and longitudinal sections) organotypic cultures (hOCs) from first trimester tissues after informed consent by donor and ethical approval by the Regional Human Ethics Committee, Stockholm (lately referred to as Swedish Ethical Review Authority), and The National Board of Health and Welfare, Sweden. We evaluated the stability of hOCs with a semi-quantitative hOC score, immunohistochemistry, flow cytometry, Ca2+signaling, and electrophysiological analysis. We also applied experimental allogeneic human neural cell therapy after injury in the ex vivo spinal cord slices.ResultsThe spinal cord hOCs presented relatively stable features during 7–21 days in vitro (DIV) (except a slightly increased cell proliferation and activated glial response). After contusion injury performed at 7 DIV, a significant reduction of the hOC score, increase of the activated caspase-3+cell population, and activated microglial populations at 14 days postinjury compared to sham controls were observed. Such elevation in the activated caspase-3+population and activated microglial population was not observed after allogeneic human neural cell therapy.ConclusionsWe conclude that human spinal cord slice cultures have potential for future structural and functional studies of human spinal cord development, injury, and treatment strategies.
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| 29. |
- Lin, CH, et al.
(author)
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In Vitro Study of Human Immune Responses to Hyaluronic Acid Hydrogels, Recombinant Spidroins and Human Neural Progenitor Cells of Relevance to Spinal Cord Injury Repair
- 2021
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In: Cells. - : MDPI AG. - 2073-4409. ; 10:7
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Journal article (peer-reviewed)abstract
- Scaffolds of recombinant spider silk protein (spidroin) and hyaluronic acid (HA) hydrogel hold promise in combination with cell therapy for spinal cord injury. However, little is known concerning the human immune response to these biomaterials and grafted human neural stem/progenitor cells (hNPCs). Here, we analyzed short- and long-term in vitro activation of immune cells in human peripheral blood mononuclear cells (hPBMCs) cultured with/without recombinant spidroins, HA hydrogels, and/or allogeneic hNPCs to assess potential host–donor interactions. Viability, proliferation and phenotype of hPBMCs were analyzed using NucleoCounter and flow cytometry. hPBMC viability was confirmed after exposure to the different biomaterials. Short-term (15 h) co-cultures of hPBMCs with spidroins, but not with HA hydrogel, resulted in a significant increase in the proportion of activated CD69+ CD4+ T cells, CD8+ T cells, B cells and NK cells, which likely was caused by residual endotoxins from the Escherichia coli expression system. The observed spidroin-induced hPBMC activation was not altered by hNPCs. It is resource-effective to evaluate human compatibility of novel biomaterials early in development of the production process to, when necessary, make alterations to minimize rejection risk. Here, we present a method to evaluate biomaterials and hPBMC compatibility in conjunction with allogeneic human cells.
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| 30. |
- Lindgren, Anders E. G., et al.
(author)
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Chemical Probes to Study ADP-Ribosylation : Synthesis and Biochemical Evaluation of Inhibitors of the Human ADP-Ribosyltransferase ARTD3/PARP3
- 2013
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 56:23, s. 9556-9568
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Journal article (peer-reviewed)abstract
- The racemic 3-(4-oxo-3,4-dihydroquinazolin-2-yl)-N-[1-(pyridin-2-yl)ethyl]propanamide, 1, has previously been identified as a potent but unselective inhibitor of diphtheria toxin-like ADP-ribosyltransferase 3 (ARTD3). Herein we describe synthesis and evaluation of SS compounds in this class. It was found that the stereochemistry is of great importance for both selectivity and potency and that substituents on the phenyl ring resulted in poor solubility. Certain variations at the meso position were tolerated and caused a large shift in the binding pose. Changes to the ethylene linker that connects the quinazolinone to the amide were also investigated but proved detrimental to binding. By combination of synthetic organic chemistry and structure-based design, two selective inhibitors of ARTD3 were discovered.
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| 31. |
- Lindgren, Anders E. G., et al.
(author)
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PARP Inhibitor with Selectivity Toward ADP-Ribosyltransferase ARTD3/PARP3
- 2013
-
In: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 8:8, s. 1698-1703
-
Journal article (peer-reviewed)abstract
- Inhibiting ADP-ribosyl transferases with PARP-inhibitors is considered a promising strategy for the treatment of many cancers and ischemia, but most of the cellular targets are poorly characterized. Here, we describe an inhibitor of ADP-ribosyltransferase-3/poly(ADP-ribose) polymerase-3 (ARTD3), a regulator of DNA repair and mitotic progression. In vitro profiling against 12, members of the enzyme family suggests selectivity for ARTD3, and crystal structures illustrate the molecular basis for inhibitor selectivity. The compound is active in cells, where it elicits ARTD3-specific effects at submicromolar concentration. Our results show that by targeting the nicotinamide binding site, selective inhibition can be achieved among the closest relatives of the validated clinical target, ADP-ribosyltransferase-1/poly(ADP-ribose) polymerase-1.
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| 32. |
- Menichetti, Lorenzo, et al.
(author)
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Increase in soil stable carbon isotope ratio relates to loss of organic carbon : results from five long-term bare fallow experiments
- 2015
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In: Oecologia. - New York : Springer Verlag. - 0029-8549 .- 1432-1939. ; 177:3, s. 811-821
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Journal article (peer-reviewed)abstract
- Changes in the 12C/13C ratio (expressed as δ13C) of soil organic C (SOC) has been observed over long time scales and with depth in soil profiles. The changes are ascribed to the different reaction kinetics of 12C and 13C isotopes and the different isotopic composition of various SOC pool components. However, experimental verification of the subtle isotopic shifts associated with SOC turnover under field conditions is scarce. We determined δ13C and SOC in soil sampled during 1929–2009 in the Ap-horizon of five European long-term bare fallow experiments kept without C inputs for 27–80 years and covering a latitudinal range of 11°. The bare fallow soils lost 33–65 % of their initial SOC content and showed a mean annual δ13C increase of 0.008–0.024 ‰. The 13C enrichment could be related empirically to SOC losses by a Rayleigh distillation equation. A more complex mechanistic relationship was also examined. The overall estimate of the fractionation coefficient (ε) was −1.2 ± 0.3 ‰. This coefficient represents an important input to studies of long-term SOC dynamics in agricultural soils that are based on variations in 13C natural abundance. The variance of ε may be ascribed to site characteristics not disclosed in our study, but the very similar kinetics measured across our five experimental sites suggest that overall site-specific factors (including climate) had a marginal influence and that it may be possible to isolate a general mechanism causing the enrichment, although pre-fallow land use may have some impact on isotope abundance and fractionation.
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| 33. |
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| 34. |
- Oja, C., et al.
(author)
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Awareness of parental illness: a grounded theory of upholding family equilibrium in parents on long-term sick-leave in primary health care
- 2021
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In: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 39:3, s. 268-278
-
Journal article (peer-reviewed)abstract
- Objective To understand the main concern of chronically ill parents and how they resolve this concern in relation to their children. Design Grounded theory. Setting Three primary health care clinics in Sweden. Subjects Thirty-two interviewed parents and their children. Main outcome measures Processes and typologies of upholding family relationships. Results A concern of chronically ill parents is sustaining family equilibrium, achieved through a process of upholding family relationships. How a parent upholds depends upon his/her comprehension of the illness and of their child's need for parenting. In response to the parent's upholding behaviours, children mirror the effect of the illness to the parent, the child's specific behaviour depending on his/her level of comprehension regarding the parent's illness. Their combined behaviours create an awareness context that may be closed, concealed, suspicious, conflicted, mutual pretence or open. When the parent drives and facilitates the evolution of comprehension, the context quickly evolves from closed to open. When the parent hinders the process by masking and resisting the child responds by probing and proving and they become locked into a suspicious or conflicted awareness context with high relational tension. To create family equilibrium the parent needs to reveal and facilitate the awareness process. Conclusion Parents on long-term sick leave in primary health care can need assistance to facilitate the awareness context of themselves and their child. Implications: Clinicians can identify the current awareness context of their patient and help their patient towards increased understanding of their illness; their child's needs and the parental capacities needed to reveal the illness and its impacts.
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| 35. |
- Oja, C., et al.
(author)
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Informing children of their parent's illness: A systematic review of intervention programs with child outcomes in all health care settings globally from inception to 2019
- 2020
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:5
-
Journal article (peer-reviewed)abstract
- Introduction Children are impacted when parents are ill. This systematic review gives an overview of the current state of research and extracts what children and parents found helpful in the interventions aimed at informing children of their parent's illness. Methods This review was registered with PROSPERO and conducted in accordance with PRISMA guidelines. Five health and social science databases were searched from inception to November 2019 to identify original, peer-reviewed articles in English describing effective interventions. The authors selected and reviewed the studies independently, and any inconsistencies were resolved by discussion in face-to-face meetings and emails. A descriptive synthesis of evidence-based concepts from quantitative and qualitative studies was conducted. Results A total of 13 892 titles and 144 full-text articles were reviewed with 32 selected for final inclusion, 21 quantitative, 11 qualitative and no mixed-method studies published from 1993 to November 2019. Most of the research was conducted in mental health, including substance abuse (n = 22), but also in cancer care (n = 6) and HIV care (n = 4). Most studies using quantitative method showed a small to moderately positive statistically significant intervention effect on the child's level of internalized symptoms. Content analysis of the results of studies employing qualitative methodology resulted in four concepts important to both children and parents in interventions (increased knowledge, more open communication, new coping strategies and changed feelings) and three additional concepts important to parents (observed changes in their children's behavior, the parent's increased understanding of their own child and the relief of respite). Conclusions In the literature there is evidence of mild to moderate positive effects on the child's level of internalized symptoms as well as concepts important to children and parent's worth noting when trying to bridge the still existing knowledge gaps. In further efforts the challenges of implementation as well as adaptation to differing clinical and personal situations appear key to address.
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| 36. |
- Oja, C., et al.
(author)
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Making life work for both themselves and their parents alone- how children aged 11-16 view themselves in relation to their chronically ill parents in a primary health care setting
- 2019
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In: International Journal of Adolescence and Youth. - : Informa UK Limited. - 0267-3843 .- 2164-4527. ; 24:4, s. 408-420
-
Journal article (peer-reviewed)abstract
- This study explores the main concern and life strategies of children whose parents are chronically ill in a Primary Health Care (PHC) center in Stockholm, Sweden. Data was collected through semi-structured individual interviews, and qualitative inductive constant comparative analysis resulted in a conceptual model. The two main strategies the children used were to understand the situation and to adopt a parental role. Children saw themselves as main contributors into the functioning of their families. Results show that these children also viewed their situation as difficult. It is an important mental health task for professionals in PHC to reach out and inform both ill parents and their children that children are very interested and involved in their parents' health. These children need respect for both their capacity and their vulnerability as they struggle to make life stable and functional for themselves and their parents. Further research and development of appropriate interventions are needed in this ethically challenging area.
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| 37. |
- Orlova, Anna, et al.
(author)
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Site-specific radiometal labeling and improved biodistribution using ABY-027, a novel HER2-targeting affibody molecule-albumin-binding domain fusion protein
- 2013
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 54:6, s. 961-968
-
Journal article (peer-reviewed)abstract
- Because of their better penetration, smaller targeting proteins may be superior to antibodies for radioimmunotherapy of solid tumors. Therefore, Affibody molecules (6.5 kDa) have a potential for being suitable as targeted moiety for radiolabeled therapeutic proteins. Previous studies have demonstrated that a fusion of an Affibody molecule with an albumin-binding domain (ABD) provides a strong noncovalent binding to albumin in vivo. This strong noncovalent binding can be used for reduction of the renal uptake of the Affibody molecule while maintaining a size smaller than that of an antibody, which is important when using residualizing radionuclide labels conjugated to Affibody molecules. The goal of this study was to design and evaluate a new targeting Affibody - ABD fusion protein with improved biodistribution properties for radionuclide therapy. Methods: A novel Affibody-based construct, Z HER2:2891-ABD035-DOTA (ABY-027), was created by fusion of the reengineered HER2-binding Affibody molecule ZHER2:2891 to the N terminus of the high-affinity ABD035, and a maleimido-derivative of DOTA was conjugated at the C terminus of the construct. Binding and processing of 177Lu-ABY-027 by HER2-expressing cells were evaluated in vitro. Targeting of HER2-expressing SKOV-3 xenografts was evaluated in BALB/C nu/nu mice and compared with targeting of previously reported ABD-(Z HER2:342)2. Results: The binding affinity (dissociation constant) of ABY-027 to HER2 (74 pM) was the same as for the parental Z HER2:2891 (76 pM). ABY-027 was stably labeled with 177Lu and 111In with preserved specific binding to HER2-expressing cells in vitro. In vivo receptor saturation experiments demonstrated that targeting of SKOV-3 xenografts in BALB/C nu/nu mice was HER2-specific. 177Lu-ABY- 027 demonstrated substantially (2- to 3-fold) lower renal and hepatic uptake than previously assessed HER2-specific Affibody-based albumin-binding agents. Tumor uptake of radiolabeled ABY-027 at 48 h after injection was 2-fold higher than that for previously reported ABD-(ZHER2:342)2. Conclusion: An optimized molecular design of an ABD fusion protein resulted in an Affibody molecule construct with better properties for therapy. Fully preserved in vivo targeting of the fusion protein was shown in xenografted mice. Site-specific coupling of DOTA provides a uniform conjugate and creates the potential for labeling with a broad range of therapeutic radionuclides. The biodistribution of 177Lu-ABY-027 in a murine model suggests it is more suitable for therapy than alternative approaches.
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| 38. |
- Rijk, Ingrid. J. C., 1985-, et al.
(author)
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Carbon and nitrogen cycling in a lead polluted grassland evaluated using stable isotopes (δ13C and δ15N) and microbial, plant and soil parameters
- 2020
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In: Plant and Soil. - : Kluwer Academic Publishers. - 0032-079X .- 1573-5036. ; 449:1-2, s. 249-266
-
Journal article (peer-reviewed)abstract
- Aims: Carbon (C) and nitrogen (N) cycling are key ecosystem functions potentially altered by heavy metal pollution. We used an ecosystem approach to study the long-term effect of lead (Pb) on C and N cycles in a natural grassland in a former shooting range.Methods: Microbial activity was evaluated by substrate-induced respiration (SIR) in situ, adding isotopically labelled C4-sugar to the soil. C and N contents and natural abundance of isotopes were measured in grass leaves, soil and microbial biomass together with root biomass.Results: A reduced microbial activity and microbial biomass per area, together with a higher soil C stock and C:N ratio suggested a lower microbial decomposition in high Pb compared to low Pb areas. A more closed N cycle in the high Pb area was indicated by 2–3‰ lower δ15N in leaves and soil compared to low Pb areas. Higher δ13C in leaves and higher root biomass but similar leaf nutrient contents indicated plant responses and adaptions to the high Pb. Conclusions: The applied ecosystem approach revealed that Pb slowed down the C and N cycles, possibly by indirect effects rather than by direct toxicity. The ecosystem seems to have adapted to altered conditions.
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| 39. |
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| 40. |
- Thomsson, Elisabeth, 1975, et al.
(author)
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Recombinant glycoprotein E produced in mammalian cells in large-scale as an antigen for varicella-zoster-virus serology.
- 2011
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In: Journal of virological methods. - : Elsevier BV. - 1879-0984 .- 0166-0934. ; 175:1, s. 53-9
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Journal article (peer-reviewed)abstract
- A recombinant glycoprotein E (gE) from varicella-zoster virus (VZV) was generated and produced in Chinese Hamster Ovary (CHO) cells, in the development of a specific antigen for analysis of IgG antibodies to VZV. Several stable gE-secreting clones were established and one clone was adapted to growth in serum-free suspension culture. When the cells were cultured in a perfusion bioreactor, gE was secreted into the medium, from where it could be easily purified. The recombinant gE was then evaluated as a serological antigen in ELISA. When compared to a conventional whole virus antigen, the VZV gE showed similar results in ELISA-based seroprevalence studies of 854 samples derived from blood donors, students, ischemic stroke patients and their controls, including samples with border-line results in previous analyses. Eight samples (0.9%) were discordant, all being IgG-negative by the VZV gE ELISA and positive by the whole virus ELISA. The sensitivity and specificity of the VZV gE ELISA were 99.9% and 100%, respectively, compared to 100% and 88.9% for the VZV whole virus ELISA. The elderly subjects showed similar reactivities to both antigens, while VZV gE gave lower signals in the younger cohorts, suggesting that antibodies to gE may increase with age. It was concluded that the recombinant VZV gE from CHO cells was suitable as a serological antigen for the detection of IgG antibodies specific for VZV.
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| 41. |
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| 42. |
- Tuisku, Jouni, et al.
(author)
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Effects of age, BMI and sex on the glial cell marker TSPO : a multicentre [11C]PBR28 HRRT PET study
- 2019
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 46:11, s. 2329-2338
-
Journal article (peer-reviewed)abstract
- Purpose The purpose of this study was to investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [C-11]PBR28. Methods [C-11]PBR28 data from 140 healthy volunteers (72 males and 68 females; N = 78 with HAB and N = 62 MAB genotype; age range 19-80 years; BMI range 17.6-36.9) were acquired with High Resolution Research Tomograph at three centres: Karolinska Institutet (N = 53), Turku PET centre (N = 62) and Yale University PET Center (N = 25). The total volume of distribution (V-T) was estimated in global grey matter, frontal, temporal, occipital and parietal cortices, hippocampus and thalamus using multilinear analysis 1. The effects of age, BMI and sex on TSPO availability were investigated using linear mixed effects model, with TSPO genotype and PET centre specified as random intercepts. Results There were significant positive correlations between age and V-T in the frontal and temporal cortex. BMI showed a significant negative correlation with V-T in all regions. Additionally, significant differences between males and females were observed in all regions, with females showing higher V-T. A subgroup analysis revealed a positive correlation between V-T and age in all regions in male subjects, whereas age showed no effect on TSPO levels in female subjects. Conclusion These findings provide evidence that individual biological properties may contribute significantly to the high variation shown in TSPO binding estimates, and suggest that age, BMI and sex can be confounding factors in clinical studies.
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| 43. |
- Wallander, Håkan, et al.
(author)
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Evaluation of methods to estimate production, biomass and turnover of ectomycorrhizal mycelium in forests soils : a review
- 2013
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In: Soil Biology and Biochemistry. - : Elsevier BV. - 0038-0717 .- 1879-3428. ; 57, s. 1034-1047
-
Research review (peer-reviewed)abstract
- Mycorrhizal fungi constitute a considerable sink for carbon in most ecosystems. This carbon is used for building extensive mycelial networks in the soil as well as for metabolic activity related to nutrient uptake. A number of methods have been developed recently to quantify production, standing biomass and turnover of extramatrical mycorrhizal mycelia (EMM) in the field. These methods include minirhizotrons, in-growth mesh bags and cores, and indirect measurements of EMM based on classification of ectomycorrhizal fungi into exploration types. Here we review the state of the art of this methodology and discuss how it can be developed and applied most effectively in the field, Furthermore, we also discuss different ways to quantify fungal biomass based on biomarkers such as chitin, ergosterol and PLFAs, as well as molecular methods, such as qPCR. The evidence thus far indicates that mycorrhizal fungi are key components of microbial biomass in many ecosystems. We highlight the need to extend the application of current methods to focus on a greater range of habitats and mycorrhizal types enabling incorporation of mycorrhizal fungal biomass and turnover into biogeochemical cycling models.
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| 44. |
- Wennerberg, Erik, et al.
(author)
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Human anaplastic thyroid carcinoma cells are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract NK cells
- 2014
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In: Clinical Cancer Research. - 1078-0432. ; 20:22, s. 5733-5744
-
Journal article (peer-reviewed)abstract
- PURPOSE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive forms of cancer with no curative therapies available. To date, strategies to target ATC by immunotherapy have not been evaluated. We investigated whether ATC would be a suitable target for natural killer (NK) cell-based immunotherapy.EXPERIMENTAL DESIGN: We first established seven new cell lines from ATC tumors, three from papillary thyroid carcinoma tumors and analyzed them together with eight additional ATC cell lines. Cells were analyzed for sensitivity to lysis by NK cells and their ability to chemoattract and regulate the activity of NK cells. In addition, fresh tumor samples and peripheral blood from six patients with ATC were analyzed for NK cell infiltration and phenotype.RESULTS: We observed that ATC cell lines are sensitive to lysis by ex vivo expanded NK cells and that the lysis was abrogated upon blockade of NKG2D. Sensitivity of thyroid cancer cell lines to NK cell-mediated lysis correlated with surface expression of UL16-binding protein 2 on tumor cells. Moreover, ATC cell lines produced high levels of CXCL10 and stimulated migration of expanded NK cells and ATC tumors were enriched for NK cells expressing the cognate chemokine receptor CXCR3. However, compared with NK cells in peripheral blood, ATC tumor-derived NK cells displayed a suppressed phenotype with a downregulated expression of NKG2D. In vitro, suppression of NK cell-mediated lysis and NKG2D expression by ATC cells was restored upon neutralization of prostaglandin-E2.CONCLUSIONS: ATC cell lines are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract CXCR3-positive NK cells. Patients with ATC may benefit from NK cell-based immunotherapy.
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| 45. |
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| 46. |
- Yuan, Xiaotian, et al.
(author)
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GABPA inhibits invasion/metastasis in papillary thyroid carcinoma by regulating DICER1 expression
- 2019
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In: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 38:7, s. 965-979
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Journal article (peer-reviewed)abstract
- The ETS family transcription factor GABPA is suggested as an oncogenic element, which is further supported by the recent reporting of it as the sole ETS member to activate the mutant TERT promoter in thyroid carcinomas (TC). However, it remains unclear how GABPA contributes to TC pathogenesis. The present study is designed to address this issue. TERT expression was significantly diminished in TERT promoter-mutated TC cells upon GABPA inhibition. Surprisingly, GABPA depletion led to robustly increased cellular invasion independently of TERT promoter mutations and TERT expression. DICER1, a component of the microRNA machinery, was identified as a downstream effector of GABPA. GABPA facilitated Dicer1 transcription while its depletion reduced Dicer1 expression. The mutation of the GABPA binding site in the DICER1 promoter led to diminished basal levels of DICER1 promoter activity and abolishment of GABPA-stimulated promoter activity as well. The forced DICER1 expression abrogated the invasiveness of GABPA-depleted TC cells. Consistently, the analyses of 93 patients with papillary thyroid carcinoma (PTC) revealed a positive correlation between GABPA and DICER1 expression. GABPA expression was negatively associated with TERT expression and promoter mutations, in contrast to published observations in cancer cell lines. Lower GABPA expression was associated with distant metastasis and shorter overall/disease-free survival in PTC patients. Similar results were obtained for PTC cases in the TCGA dataset. In addition, a positive correlation between GABPA and DICER1 expression was seen in multiple types of malignancies. Taken together, despite its stimulatory effect on the mutant TERT promoter and telomerase activation, GABPA may itself act as a tumor suppressor rather than an oncogenic factor to inhibit invasion/metastasis in TCs and be a useful predictor for patient outcomes.
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| 47. |
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| 48. |
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| 49. |
- Zhao, J., et al.
(author)
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Transdifferentiation of autologous bone marrow cells on a collagen-poly(epsilon-caprolactone) scaffold for tissue engineering in complete lack of native urothelium
- 2014
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In: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 11:96
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Journal article (peer-reviewed)abstract
- Urological reconstructive surgery is sometimes hampered by a lack of tissue. In some cases, autologous urothelial cells (UCs) are not available for cell expansion and ordinary tissue engineering. In these cases, we wanted to explore whether autologous mesenchymal stem cells (MSCs) from bone marrow could be used to create urological transplants. MSCs from human bone marrow were cultured in vitro with medium conditioned by normal human UCs or by indirect co-culturing in culture well inserts. Changes in gene expression, protein expression and cell morphology were studied after two weeks using western blot, RT-PCR and immune staining. Cells cultured in standard epithelial growth medium served as controls. Bone marrow MSCs changed their phenotype with respect to growth characteristics and cell morphology, as well as gene and protein expression, to a UC lineage in both culture methods, but not in controls. Urothelial differentiation was also accomplished in human bone marrow MSCs seeded on a three-dimensional poly(epsilon-caprolactone) (PCL)-collagen construct. Human MSCs could easily be harvested by bone marrow aspiration and expanded and differentiated into urothelium. Differentiation could take place on a three-dimensional hybrid PCL-reinforced collagen-based scaffold for creation of a tissue-engineered autologous transplant for urological reconstructive surgery.
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