| 1. |
- Aevarsson, Arnthór, et al.
(författare)
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Going to extremes - a metagenomic journey into the dark matter of life
- 2021
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Ingår i: FEMS Microbiology Letters. - : Oxford University Press (OUP). - 1574-6968. ; 368:12
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Forskningsöversikt (refereegranskat)abstract
- The Virus-X-Viral Metagenomics for Innovation Value-project was a scientific expedition to explore and exploit uncharted territory of genetic diversity in extreme natural environments such as geothermal hot springs and deep-sea ocean ecosystems. Specifically, the project was set to analyse and exploit viral metagenomes with the ultimate goal of developing new gene products with high innovation value for applications in biotechnology, pharmaceutical, medical, and the life science sectors. Viral gene pool analysis is also essential to obtain fundamental insight into ecosystem dynamics and to investigate how viruses influence the evolution of microbes and multicellular organisms. The Virus-X Consortium, established in 2016, included experts from eight European countries. The unique approach based on high throughput bioinformatics technologies combined with structural and functional studies resulted in the development of a biodiscovery pipeline of significant capacity and scale. The activities within the Virus-X consortium cover the entire range from bioprospecting and methods development in bioinformatics to protein production and characterisation, with the final goal of translating our results into new products for the bioeconomy. The significant impact the consortium made in all of these areas was possible due to the successful cooperation between expert teams that worked together to solve a complex scientific problem using state-of-the-art technologies as well as developing novel tools to explore the virosphere, widely considered as the last great frontier of life.
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| 2. |
- Ahlgren, Serina, et al.
(författare)
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Description of the Agrosfär model – a tool for climate impact assessment of crop and animal production systems in Sweden : Version 1: Crops, milk and beef
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The agricultural sector in Sweden needs to cut GHG emissions and contribute to the climate goal of net-zero emissions by 2045. The GHG reduction goal for agricultural emissions is not quantified, but the Swedish climate policy framework states that ‘the Swedish food production shall increase as much as possible with as little climate impact as possible’ and multiple key actors within the sector of food and agriculture have developed roadmaps or industry specific goals for reducing GHG emissions from the sector. Consequently, requirements of transparent GHG accounting and reporting are increasing within the agricultural sector, both at national and international level. The purpose of the Agrosfär tool is to establish an automatic data driven climate calculator used to calculate GHG emissions from agricultural products and on farm enterprise level. The automation and automatic data collection will save time, increase accuracy of the calculations, and simplify updates of the tool to keep it aligned with the most recent climate data and climate reporting methodology. It will make it possible to continuously carry out follow-ups on climate performance indicators and measure improvements from climate measures taken. A working group consisting of Swedish agricultural life cycle assessment experts have developed the framework of the tool, e.g. setting system boundaries, selecting methodologies and input data. A technical team has developed algorithms, a digital interface and coupled the tool to other existing agricultural databases providing farm specific information on crop and animal production data, soil characteristics, carbon footprints and amounts of purchased inputs etc. The tool and user interface have been developed based on input from farmers through prototyping and in-depth interviews. For general guidelines on methodology the calculation model follows the Product Environmental Footprint Category Rules (PEFCR), the International Dairy Federation (IDF)’s approach for carbon footprint for the dairy sector and FAO Livestock Environmental Assessment and Performance guidelines (FAO LEAP). Where standards have diverged or where assumptions have been required the working group has made expert judgements on which method/guideline to follow or what assumptions to make. A first version of the tool, a so called minimal viable product (MVP) has been developed which will be the basis for further development. The MVP contains an animal and crop module and can calculate the carbon footprint of crops, milk and beef. Future development possibilities of the tool and calculation model is described in chapter 7, such as enabling climate calculations on enterprise level, develop modules for more animal production types, deepen the integration between the crop and animal modules, expand sources for automatic data collection, develop a carbon sequestration module and other technical and methodological improvements to ensure alignment with important climate reporting standards. The report will be repeatedly updated as the tool develops, and new versions of the tool are released.
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| 3. |
- Ahlgren, Serina, et al.
(författare)
-
Description of the Agrosfär model – a tool for the climate impact assessment of farms, crop and animal production systems in Sweden
- 2024
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The agricultural sector in Sweden needs to cut GHG emissions and contribute to the climate goal of net-zero emissions by 2045. The GHG reduction goal for agricultural emissions is not quantified, but the Swedish climate policy framework states that ‘Swedish food production shall increase as much as possible with as little climate impact as possible’. Multiple key actors within the sector of food and agriculture have developed roadmaps or industry specific goals for reducing GHG emissions from the sector. Consequently, requirements for transparent GHG accounting and reporting are increasing within the agricultural sector, both on a national and international level. The purpose of the Agrosfär tool is to establish an automatic data driven climate calculator used to calculate GHG emissions from agricultural products and on a farm enterprise level. Automation and automatic data collection will save time, increase the accuracy of the calculations, and simplify updates of the tool to keep it aligned with the most recent climate data and climate reporting methodology. It will make it possible to continuously carry out follow-ups on climate performance indicators and measure improvements from climate measures taken. A working group consisting of agricultural life cycle assessment experts has developed the framework of the tool (e.g., setting system boundaries, selecting methodologies and input data). A technical team has developed algorithms, a digital interface and coupled the tool to other existing agricultural databases, providing farm specific information on crop and animal production data, soil characteristics, carbon footprints and amounts of purchased inputs etc. The tool and user interface have been developed based on input from farmers through prototyping and in-depth interviews. The priority guidelines on which the calculation model is based are the Product Environmental Footprint Category Rules (PEFCR), the International Dairy Federation (IDF)’s approach for carbon footprint for the dairy sector, and FAO Livestock Environmental Assessment and Performance guidelines (FAO LEAP). From the farm perspective, the Greenhouse Gas Protocol (GHG Protocol) Corporate Standard, GHG Protocol Agricultural Guidance (Scope 1 & 2) and GHG Protocol Corporate value chain (Scope 3) Accounting and Reporting Standard are guiding standards. Where standards have diverged or where assumptions have been required, the working group has made expert judgements on which method/guideline to follow or what assumptions to make. A first version of the tool, first described in report version 1, was developed as the basis for further development. The first version contains an animal and a crop module, and can calculate the carbon footprint of crops, milk and beef. This report (version 1.1) has been updated to include the most recent developments of the tool. The main change is that the tool can now also be used to calculate farm climate impact on a yearly basis. Future possibilities to develop the tool and calculation model are described in chapter 7, including suggestions for developing modules for more animal production types, deepening the integration between the crop and animal modules, expanding sources for automatic data collection, developing a carbon sequestration module, and other technical and methodological improvements to ensure alignment with important climate reporting standards. The report will be repeatedly updated as the tool develops, and new versions of the tool are released.
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| 4. |
- Barmpatsalou, Vicky, et al.
(författare)
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Development and validation of a porcine artificial colonic mucus model reflecting the properties of native colonic mucus in pigs
- 2023
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 181
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Tidskriftsartikel (refereegranskat)abstract
- Colonic mucus plays a key role in colonic drug absorption. Mucus permeation assays could therefore provide useful insights and support rational formulation development in the early stages of drug development. However, the collection of native colonic mucus from animal sources is labor-intensive, does not yield amounts that allow for routine experimentation, and raises ethical concerns. In the present study, we developed an in vitro porcine artificial colonic mucus model based on the characterization of native colonic mucus. The structural properties of the artificial colonic mucus were validated against the native secretion for their ability to capture key diffusion patterns of macromolecules in native mucus. Moreover, the artificial colonic mucus could be stored under common laboratory conditions, without compromising its barrier properties. In conclusion, the porcine artificial colonic mucus model can be considered a biorelevant way to study the diffusion behavior of drug candidates in colonic mucus. It is a cost-efficient screening tool easily incorporated into the early stages of drug development and it contributes to the implementation of the 3Rs (refinement, reduction, and replacement of animals) in the drug development process.
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| 5. |
- Barmpatsalou, Vicky, et al.
(författare)
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Physiological properties, composition and structural profiling of porcine gastrointestinal mucus
- 2021
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 169, s. 156-167
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Tidskriftsartikel (refereegranskat)abstract
- The gastrointestinal mucus is a hydrogel that lines the luminal side of the gastrointestinal epithelium, offering barrier protection from pathogens and lubrication of the intraluminal contents. These barrier properties likewise affect nutrients and drugs that need to penetrate the mucus to reach the epithelium prior to absorption. In order to assess the potential impact of the mucus on drug absorption, we need information about the nature of the gastrointestinal mucus. Today, most of the relevant available literature is mainly derived from rodent studies. In this work, we used a larger animal species, the pig model, to characterize the mucus throughout the length of the gastrointestinal tract. This is the first report of the physiological properties (physical appearance, pH and water content), composition (protein, lipid and metabolite content) and structural profiling (rheology and gel network) of the porcine gastrointestinal mucus. These findings allow for direct comparisons between the characteristics of mucus from various segments and can be further utilized to improve our understanding of the role of the mucus on region dependent drug absorption. Additionally, the present work is expected to contribute to the assessment of the porcine model as a preclinical species in the drug development process.
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| 6. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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Life expectancy after bariatric surgery or usual care in patients with or without baseline type 2 diabetes in Swedish Obese Subjects.
- 2023
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Ingår i: International journal of obesity (2005). - 1476-5497. ; 47, s. 931-8
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Tidskriftsartikel (refereegranskat)abstract
- To determine life expectancy and causes of death after bariatric surgery in relation to baseline type 2 diabetes (T2D) in the prospective, Swedish Obese Subjects study.The study included 2010 patients with obesity who underwent bariatric surgery and 2037 matched controls, eligible for surgery. The surgery group underwent gastric bypass (n=265), banding (n=376), or vertical banded gastroplasty (n=1369). The control group (n=2037) received usual obesity care. Causes of death were obtained from the Swedish Cause of Death Register, case sheets and autopsy reports, in patients with baseline T2D (n=392 surgery patients/n=305 controls) or non-T2D (n=1609 surgery patients/n=1726 controls) during a median follow-up 26 years.In T2D and non-T2D subgroups, bariatric surgery was associated with increased life expectancy (2.1, 95% confidence interval (95% CI) 0.2-4.0; and 1.6, 0.5-2.7 years, respectively) and reduced overall mortality (adjusted hazard ratio (adjHR)=0.77, 95% CI: 0.61-0.97; and 0.82, 0.72-0.94, respectively), and the treatment benefit was similar (interaction p=0.615). Bariatric surgery was associated with reduced cardiovascular mortality in both subgroups (adjHR=0.65, 95% CI: 0.46-0.91; and 0.70, 0.55-0.88, respectively (interaction p=0.516)).Bariatric surgery is associated with similar reduction of overall and cardiovascular mortality and increased life expectancy regardless of baseline diabetes status.
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| 7. |
- Jasilionis, Andrius, et al.
(författare)
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AmiP from hyperthermophilic Thermus parvatiensis prophage is a thermoactive and ultrathermostable peptidoglycan lytic amidase
- 2023
-
Ingår i: Protein Science. - : Wiley. - 1469-896X .- 0961-8368. ; 32:3, s. 4585-4585
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Tidskriftsartikel (refereegranskat)abstract
- Bacteriophages encode a wide variety of cell wall disrupting enzymes that aid the viral escape in the final stages of infection. These lytic enzymes have accumulated notable interest due to their potential as novel antibacterials for infection treatment caused by multiple-drug resistant bacteria. Here, the detailed functional and structural characterization of Thermus parvatiensis prophage peptidoglycan lytic amidase AmiP, a globular Amidase_3 type lytic enzyme adapted to high temperatures is presented. The sequence and structure comparison with homologous lytic amidases reveals the key adaptation traits that ensure the activity and stability of AmiP at high temperatures. The crystal structure determined at a resolution of 1.8 Å displays a compact α/β-fold with multiple secondary structure elements omitted or shortened compared with protein structures of similar proteins. The functional characterization of AmiP demonstrates high efficiency of catalytic activity and broad substrate specificity toward thermophilic and mesophilic bacteria strains containing Orn-type or DAP-type peptidoglycan. The here presented AmiP constitutes the most thermoactive and ultrathermostable Amidase_3 type lytic enzyme biochemically characterized with a temperature optimum at 85°C. The extraordinary high melting temperature Tm 102.6°C confirms fold stability up to approximately 100°C. Furthermore, AmiP is shown to be more active over the alkaline pH range with pH optimum at pH 8.5 and tolerates NaCl up to 300 mM with the activity optimum at 25 mM NaCl. This set of beneficial characteristics suggests that AmiP can be further exploited in biotechnology.
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| 8. |
- Karlsson, Thomas, et al.
(författare)
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Ett stort Sorbus eller flera släkten
- 2020
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Ingår i: Svensk Botanisk Tidskrift. - 0039-646X. ; 114, s. 196-199
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 9. |
- Ortenlöf, Niklas, et al.
(författare)
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Characterization of choroid plexus in the preterm rabbit pup following subcutaneous administration of recombinant human IGF-1/IGFBP-3
- 2023
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Ingår i: Fluids and Barriers of the CNS. - 2045-8118. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates essential processes of vascular maturation and stabilization. Importantly, preterm birth is associated with reduced serum levels of IGF-1 as compared to in utero levels. Using a preterm rabbit pup model, we investigated the uptake of systemic recombinant human (rh) IGF-1 in complex with its main binding protein IGF-binding protein 3 (BP-3) to the brain parenchyma via the choroid plexus. Five hours after subcutaneous administration, labeled rhIGF-1/rhIGFBP-3 displayed a widespread presence in the choroid plexus of the lateral and third ventricle, however, to a less degree in the fourth, as well as in the perivascular and subarachnoid space. We found a time-dependent uptake of IGF-1 in cerebrospinal fluid, decreasing with postnatal age, and a translocation of IGF-1 through the choroid plexus. The impact of systemic rhIGF-1/rhIGFBP-3 on IGF-1 receptor activation in the choroid plexus decreased with postnatal age, correlating with IGF-1 uptake in cerebrospinal fluid. In addition, choroid plexus gene expression was observed to increase with postnatal age. Moreover, using choroid plexus in vitro cell cultures, gene expression and protein synthesis were further investigated upon rhIGF-1/rhIGFBP-3 stimulation as compared to rhIGF-1 alone, and found not to be differently altered. Here, we characterize the uptake of systemic rhIGF-1/rhIGFBP-3 to the preterm brain, and show that the interaction between systemic rhIGF-1/rhIGFBP-3 and choroid plexus varies over time.
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| 10. |
- Radke, Katarzyna, et al.
(författare)
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Anti-tumor effects of rigosertib in high-risk neuroblastoma
- 2021
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Ingår i: Translational Oncology. - : Elsevier BV. - 1936-5233. ; 14:8
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Tidskriftsartikel (refereegranskat)abstract
- High-risk neuroblastoma has a poor prognosis despite intense treatment, demonstrating the need for new therapeutic strategies. Here we evaluated the effects of rigosertib (ON-01910.Na) in preclinical models of high-risk neuroblastoma. Among several hundred cancer cell lines representing 24 tumor types, neuroblastoma was the most sensitive to rigosertib. Treatment of MYCN-amplified neuroblastoma organoids resulted in organoid disintegration, decreased cell viability, and increased apoptotic cell death. Neuroblastoma response to rigosertib involved G2M cell cycle arrest and decreased phosphorylation of AKT (Ser473) and ERK1/2 (Thr202/Tyr204). Rigosertib delayed tumor growth and prolonged survival of mice carrying neuroblastoma MYCN-amplified PDX tumors (median survival: 31 days, treated; 22 days, vehicle) accompanied with increased apoptosis in treated tumors. We further identified vincristine and rigosertib as a potential promising drug combination treatment. Our results show that rigosertib might be a useful therapeutic agent for MYCN-amplified neuroblastomas, especially in combination with existing agents.
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