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| 3. |
- Andersson, Sören, 1957-, et al.
(författare)
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CHIMERIC MOMP ANTIGEN
- 2015
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Patent (populärvet., debatt m.m.)
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| 4. |
- Xu, Bo, 1980-
(författare)
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Evolutionary and Pharmacological Studies of NPY and QRFP Receptors
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The neuropeptide Y (NPY) system consists of 3-4 peptides and 4-7 receptors in vertebrates. It has powerful effects on appetite regulation and is involved in many other biological processes including blood pressure regulation, bone formation and anxiety. This thesis describes studies of the evolution of the NPY system by comparison of several vertebrate species and structural studies of the human Y2 receptor, which reduces appetite, to identify amino acid residues involved in peptide-receptor interactions.The NPY system was studied in zebrafish (Danio rerio), western clawed frog (Xenopus tropicalis), and sea lamprey (Petromyzon marinus). The receptors were cloned and functionally expressed and their pharmacological profiles were determined using the native peptides in either binding studies or a signal transduction assay. Some peptide-receptor preferences were observed, indicating functional specialization.A receptor family closely related to the NPY receptors, called the QRFP receptors, was investigated. A QRFP receptor was cloned from amphioxus, Branchistoma floridae, showing that the receptor arose before the origin of the vertebrates. Evolutionary studies demonstrated that the ancestral vertebrate had as many as four QRFP receptors, only one of which remains in mammals today. This correlates with the NPY receptor family, located in the same chromosomal regions, which had seven members in the ancestral vertebrate but only 4-5 in living mammals. Some vertebrates have considerably more complex NPY and QRFP receptor systems than humans and other mammals.Two studies investigated interactions of NPY-family peptides with the human Y2 receptor. Candidate residues, selected based on structural modeling and docking, were mutated to disrupt possible interactions with peptide ligands. The modified receptors were expressed in cultured cells and investigated by measuring binding and functional responses. Several receptor residues were found to influence peptide-receptor interactions, some of which are involved in maintaining receptor structure. In a pilot study, the kinetics of peptide-receptor interaction were found to be very slow, of the order several hours.In conclusion, this thesis clarifies evolutionary relationships for the complex NPY and QRFP peptide-receptor systems and improves the structural models of the human NPY-family receptors, especially Y2. These results will hopefully facilitate drug design for targeting of NPY-family receptors.
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| 5. |
- Rolfö, Linda, et al.
(författare)
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Predictors of Preference for the Activity-based Flexible Office
- 2019
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Ingår i: Human Systems Engineering and Design. - Cham : Springer. - 9783030020521 - 9783030020538 ; 876, s. 547-553
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Konferensbidrag (refereegranskat)abstract
- Activity-based Flexible Offices (A-FOs) are implemented with varying degree of success. Employees relocate from cell or open-plan offices, from different organizational backgrounds, varying design and implementation processes, and have different types of work tasks. This study aims at investigating whether preference for the A-FO correlate with these preconditions. The results from Chi-square tests and Spearman’s non-parametric correlation of post-relocation questionnaires distributed to 11 A-FO sites, showed that a high preference for the A-FO correlated strongest with an A-FO preference prior to relocation, being a former open-plan office occupier and with frequent performance of innovation. Low preference for the A-FO correlated with frequent performance of concentration demanding tasks. Working with tasks with high confidentiality did not predict the preference ratings.
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| 6. |
- Syberg, K., et al.
(författare)
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Toward a Conceptual Approach for Assessing Risks from Chemical Mixtures and Other Stressors to Coastal Ecosystem Services
- 2017
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Ingår i: Integrated Environmental Assessment and Management. - : Wiley. - 1551-3777 .- 1551-3793. ; 13:2, s. 376-386
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Tidskriftsartikel (refereegranskat)abstract
- Growth of human populations and increased human activity, particularly in coastal areas, increase pressure on coastal ecosystems and the ecosystem services (ES) they provide. As a means toward being able to assess the impact of multiple stressors on ES, in the present study we propose an 8-step conceptual approach for assessing effects of chemical mixtures and other stressors on ES in coastal areas: step A, identify the relevant problems and policy aims; step B, identify temporal and spatial boundaries; step C, identify relevant ES; step D, identify relevant stressors (e.g., chemicals); step E, translate impacts into ES units; step F, assess cumulative risk in ES units; step G, rank stressors based on their contribution to adverse effects on ES; and step H, implement regulation and management as appropriate and necessary. Two illustrative case studies (Swedish coastal waters and a coastal lagoon in Costa Rica) are provided; one focuses on chemicals that affect human food supply and the other addresses pesticide runoff and trade-offs among ES. The 2 cases are used to highlight challenges of such risk assessments, including use of standardized versus ES-relevant test species, data completeness, and trade-offs among ES. Lessons learned from the 2 case studies are discussed in relation to environmental risk assessment and management of chemical mixtures. Integr Environ Assess Manag 2017;13:376-386. (C) 2016 SETAC
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| 7. |
- Ågren, Rasmus, 1982, et al.
(författare)
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Identification of anticancer drugs for hepatocellular carcinoma through personalized genome-scale metabolic modeling
- 2014
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Synopsis Personalized GEMs for six hepatocellular carcinoma patients are reconstructed using proteomics data and a task-driven model reconstruction algorithm. These GEMs are used to predict antimetabolites preventing tumor growth in all patients or in individual patients. The presence of proteins encoded by 15,841 genes in tumors from 27 HCC patients is evaluated by immunohistochemistry. Personalized GEMs for six HCC patients and GEMs for 83 healthy cell types are reconstructed based on HMR 2.0 and the tINIT algorithm for task-driven model reconstruction. 101 antimetabolites are predicted to inhibit tumor growth in all patients. Antimetabolite toxicity is tested using the 83 cell type-specific GEMs. Genome-scale metabolic models (GEMs) have proven useful as scaffolds for the integration of omics data for understanding the genotype-phenotype relationship in a mechanistic manner. Here, we evaluated the presence/absence of proteins encoded by 15,841 genes in 27 hepatocellular carcinoma (HCC) patients using immunohistochemistry. We used this information to reconstruct personalized GEMs for six HCC patients based on the proteomics data, HMR 2.0, and a task-driven model reconstruction algorithm (tINIT). The personalized GEMs were employed to identify anticancer drugs using the concept of antimetabolites; i.e., drugs that are structural analogs to metabolites. The toxicity of each antimetabolite was predicted by assessing the in silico functionality of 83 healthy cell type-specific GEMs, which were also reconstructed with the tINIT algorithm. We predicted 101 antimetabolites that could be effective in preventing tumor growth in all HCC patients, and 46 antimetabolites which were specific to individual patients. Twenty-two of the 101 predicted antimetabolites have already been used in different cancer treatment strategies, while the remaining antimetabolites represent new potential drugs. Finally, one of the identified targets was validated experimentally, and it was confirmed to attenuate growth of the HepG2 cell line.
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| 8. |
- Gyllensten, Hanna, 1979, et al.
(författare)
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Economic Impact of Adverse Drug Events – A Retrospective Population-Based Cohort Study of 4970 Adults
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Background The aim was to estimate the direct costs caused by ADEs, including costs for dispensed drugs, primary care, other outpatient care, and inpatient care, and to relate the direct costs caused by ADEs to the societal COI (direct and indirect costs), for patients with ADEs and for the entire study population. Methods We conducted a population-based observational retrospective cohort study of ADEs identified from medical records. From a random sample of 5025 adults in a Swedish county council, 4970 were included in the analyses. During a three-month study period in 2008, direct and indirect costs were estimated from resource use identified in the medical records and from register data on costs for resource use. Results Among 596 patients with ADEs, the average direct costs per patient caused by ADEs were USD 444.9 [95% CI: 264.4 to 625.3], corresponding to USD 21 million per 100 000 adult inhabitants per year. Inpatient care accounted for 53.9% of all direct costs caused by ADEs. For patients with ADEs, the average societal cost of illness was USD 6235.0 [5442.8 to 7027.2], of which direct costs were USD 2830.1 [2260.7 to 3399.4] (45%), and indirect costs USD 3404.9 [2899.3 to 3910.4] (55%). The societal cost of illness was higher for patients with ADEs compared to other patients. ADEs caused 9.5% of all direct healthcare costs in the study population. Conclusions Healthcare costs for patients with ADEs are substantial across different settings; in primary care, other outpatient care and inpatient care. Hence the economic impact of ADEs will be underestimated in studies focusing on inpatient ADEs alone. Moreover, the high proportion of indirect costs in the societal COI for patients with ADEs suggests that the observed costs caused by ADEs would be even higher if including indirect costs. Additional studies are needed to identify interventions to prevent and manage ADEs.
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| 9. |
- Ašmonaitė, Giedrė, 1989, et al.
(författare)
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Size matters: ingestion of relatively large microplastics contaminated with environmental pollutants posed little risk for fish health and fillet quality.
- 2018
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Ingår i: Environmental science & technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X.
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we investigated biological effects associated with ingestion of polystyrene (PS) microplastic (MPs) in fish. We examined whether ingestion of contaminated PS MPs (100-400 µm) results in chemical stress in rainbow trout (Oncorhynchus mykiss) liver and we explored whether this exposure can affect the oxidative stability of the fillet during ice storage. Juvenile rainbow trout were fed for 4 weeks with four different experimental diets: control (1) and feeds containing virgin PS MPs (2) or PS MPs exposed to sewage (3) or harbor (4) effluent. A suite of ecotoxicological biomarkers for oxidative stress and xenobiotic-related pathways was investigated in the hepatic tissue, and included gene expression analyses and enzymatic measurements. The potential impact of MPs exposure on fillet quality was investigated in a storage trial where lipid hydroperoxides, loss of redness and development of rancid odor were assessed as indications of lipid peroxidation. Although, chemical analysis of PS MPs revealed that particles sorb environmental contaminants (e.g. PAHs, nonylphenol and alcohol ethoxylates and others), the ingestion of relatively high doses of these PS MPs did not induce adverse hepatic stress in fish liver. Apart from a small effect on redness loss in fillets, PS MPs ingestion did not affect lipid peroxidation or rancid odor development, thus did not affecting fillet's quality.
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| 10. |
- Scholz, Birger, et al.
(författare)
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Neuropeptidomic analysis of the embryonic Japanese quail diencephalon
- 2010
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Ingår i: BMC Developmental Biology. - 1471-213X. ; 10, s. 30-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Endogenous peptides such as neuropeptides are involved in numerous biological processes in the fully developed brain but very little is known about their role in brain development. Japanese quail is a commonly used bird model for studying sexual dimorphic brain development, especially adult male copulatory behavior in relation to manipulations of the embryonic endocrine system. This study uses a label-free liquid chromatography mass spectrometry approach to analyze the influence of age (embryonic days 12 vs 17), sex and embryonic day 3 ethinylestradiol exposure on the expression of multiple endogenous peptides in the developing diencephalon.Results: We identified a total of 65 peptides whereof 38 were sufficiently present in all groups for statistical analysis. Age was the most defining variable in the data and sex had the least impact. Most identified peptides were more highly expressed in embryonic day 17. The top candidates for EE2 exposure and sex effects were neuropeptide K (downregulated by EE2 in males and females), gastrin-releasing peptide (more highly expressed in control and EE2 exposed males) and gonadotropin-inhibiting hormone related protein 2 (more highly expressed in control males and displaying interaction effects between age and sex). We also report a new potential secretogranin-2 derived neuropeptide and previously unknown phosphorylations in the C-terminal flanking protachykinin 1 neuropeptide.Conclusions: This study is the first larger study on endogenous peptides in the developing brain and implies a previously unknown role for a number of neuropeptides in middle to late avian embryogenesis. It demonstrates the power of label-free liquid chromatography mass spectrometry to analyze the expression of multiple endogenous peptides and the potential to detect new putative peptide candidates in a developmental model.
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