| 1. |
- Diaz Cruz, Maria Araceli, et al.
(författare)
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Characterization of methylation patterns associated with lifestyle factors and vitamin D supplementation in a healthy elderly cohort from Southwest Sweden
- 2022
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Ingår i: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have shown that lifestyle factors, such as regular physical activity and vitamin D intake, may remarkably improve overall health and mental wellbeing. This is especially important in older adults whose vitamin D deficiency occurs with a high prevalence. This study aimed to examine the influence of lifestyle and vitamin D on global DNA methylation patterns in an elderly cohort in Southwest of Sweden. We also sought to examine the methylation levels of specific genes involved in vitamin D's molecular and metabolic activated pathways. We performed a genome wide methylation analysis, using Illumina Infinium DNA Methylation EPIC 850kBeadChip array, on 277 healthy individuals from Southwest Sweden at the age of 70-95. The study participants also answered queries on lifestyle, vitamin intake, heart medication, and estimated health. Vitamin D intake did not in general affect methylation patterns, which is in concert with other studies. However, when comparing the group of individuals taking vitamin supplements, including vitamin D, with those not taking supplements, a difference in methylation in the solute carrier family 25 (SCL25A24) gene was found. This confirms a previous finding, where changes in expression of SLC25A24 were associated with vitamin D treatment in human monocytes. The combination of vitamin D intake and high physical activity increased methylation of genes linked to regulation of vitamin D receptor pathway, the Wnt pathway and general cancer processes. To our knowledge, this is the first study detecting epigenetic markers associated with the combined effects of vitamin D supplementation and high physical activity. These results deserve to be further investigated in an extended, interventional study cohort, where also the levels of 25(OH)D3 can be monitored.
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| 2. |
- Ekstrand, Eva-Maria, 1985-, et al.
(författare)
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Identifying targets for increased biogasproduction through chemical and organicmatter characterization of digestate from full‑scale biogas plants : what remains and why?
- 2022
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Ingår i: Biotechnology for Biofuels and Bioproducts. - London, United Kingdom : BioMed Central. - 2731-3654. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study examines the destiny of macromolecules in different full-scale biogas processes. From previousstudies it is clear that the residual organic matter in outgoing digestates can have significant biogas potential,but the factors dictating the size and composition of this residual fraction and how they correlate with the residualmethane potential (RMP) are not fully understood. The aim of this study was to generate additional knowledge of thecomposition of residual digestate fractions and to understand how they correlate with various operational and chemicalparameters. The organic composition of both the substrates and digestates from nine biogas plants operating onfood waste, sewage sludge, or agricultural waste was characterized and the residual organic fractions were linked tosubstrate type, trace metal content, ammonia concentration, operational parameters, RMP, and enzyme activity.Results: Carbohydrates represented the largest fraction of the total VS (32–68%) in most substrates. However, inthe digestates protein was instead the most abundant residual macromolecule in almost all plants (3–21 g/kg). Thedegradation efficiency of proteins generally lower (28–79%) compared to carbohydrates (67–94%) and fats (86–91%).High residual protein content was coupled to recalcitrant protein fractions and microbial biomass, either from thesubstrate or formed in the degradation process. Co-digesting sewage sludge with fat increased the protein degradationefficiency with 18%, possibly through a priming mechanism where addition of easily degradable substrates alsotriggers the degradation of more complex fractions. In this study, high residual methane production (> 140 L CH4/kgVS) was firstly coupled to operation at unstable process conditions caused mainly by ammonia inhibition (0.74 mgNH3-N/kg) and/or trace element deficiency and, secondly, to short hydraulic retention time (HRT) (55 days) relative tothe slow digestion of agricultural waste and manure.Conclusions: Operation at unstable conditions was one reason for the high residual macromolecule content andhigh RMP. The outgoing protein content was relatively high in all digesters and improving the degradation of proteinsrepresents one important way to increase the VS reduction and methane production in biogas plants. Post-treatment
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| 3. |
- Karlsson, Lars O, 1975, et al.
(författare)
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Constitutive PGC-1α Overexpression in Skeletal Muscle Does Not Contribute to Exercise-Induced Neurogenesis.
- 2021
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Ingår i: Molecular neurobiology. - : Springer Science and Business Media LLC. - 1559-1182 .- 0893-7648. ; 58, s. 1465-1481
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Tidskriftsartikel (refereegranskat)abstract
- Physical exercise can improve age-dependent decline in cognition, which in rodent is partly mediated by restoration of an age-dependent decline in neurogenesis. Exercise-inducible myokines in the circulation present a link in muscle-brain crosstalk. The transcription factor PGC-1α regulates the release of such myokines with neurotrophic properties into the circulation. We study how chronic muscular overexpression of PGC-1α could contribute to exercise-induced effects on hippocampal neurogenesis and if this effect could be enhanced in a running wheel paradigm. We used 3- and 11-month-old transgenic mice with overexpression of PGC-1α under the control of muscle creatinine kinase promoter (MCK-PGC-1α), which have a constitutively developed endurance muscle phenotype. Wild-type and MCK-PGC-1α mice were single housed with free access to running wheels. Four weeks of running in female animals increased the levels of newborn cells, immature neurons, and, for young animals, new mature neurons, compared to sedentary controls. However, no difference in these parameters was observed between wild-type and transgenic mice under sedentary or running conditions. Multiplex analysis of serum cytokines, chemokines, and myokines suggested several differences in serum protein concentrations between genotypes with musclin found to be significantly upregulated 4-fold in male MCK-PGC-1α animals. We conclude that constitutive muscular overexpression of PGC-1α, despite systemic changes and difference in serum composition, does not translate into exercise-induced effects on hippocampal neurogenesis, independent of the age of the animal. This suggests that chronic activation of PGC-1α in skeletal muscle is by itself not sufficient to mimic exercise-induced effects or to prevent decline of neurogenesis in aging.
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| 4. |
- Alijagic, Andi, 1992-, et al.
(författare)
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A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles
- 2023
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.
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| 5. |
- Alijagic, Andi, 1992-, et al.
(författare)
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Immunotoxic, genotoxic, and endocrine disrupting impacts of polyamide microplastic particles and chemicals
- 2024
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 183
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Tidskriftsartikel (refereegranskat)abstract
- Due to their exceptional properties and cost effectiveness, polyamides or nylons have emerged as widely used materials, revolutionizing diverse industries, including industrial 3D printing or additive manufacturing (AM). Powder-based AM technologies employ tonnes of polyamide microplastics to produce complex components every year. However, the lack of comprehensive toxicity assessment of particulate polyamides and polyamide-associated chemicals, especially in the light of the global microplastics crisis, calls for urgent action. This study investigated the physicochemical properties of polyamide-12 microplastics used in AM, and assessed a number of toxicity endpoints focusing on inflammation, immunometabolism, genotoxicity, aryl hydrocarbon receptor (AhR) activation, endocrine disruption, and cell morphology. Specifically, microplastics examination by means of field emission scanning electron microscopy revealed that work flow reuse of material created a fraction of smaller particles with an average size of 1-5 µm, a size range readily available for uptake by human cells. Moreover, chemical analysis by means of gas chromatography high-resolution mass spectrometry detected several polyamide-associated chemicals including starting material, plasticizer, thermal stabilizer/antioxidant, and migrating slip additive. Even if polyamide particles and chemicals did not induce an acute inflammatory response, repeated and prolonged exposure of human primary macrophages disclosed a steady increase in the levels of proinflammatory chemokine Interleukin-8 (IL-8/CXCL-8). Moreover, targeted metabolomics disclosed that polyamide particles modulated the kynurenine pathway and some of its key metabolites. The p53-responsive luciferase reporter gene assay showed that particles per se were able to activate p53, being indicative of a genotoxic stress. Polyamide-associated chemicals triggered moderate activation of AhR and elicited anti-androgenic activity. Finally, a high-throughput and non-targeted morphological profiling by Cell Painting assay outlined major sites of bioactivity of polyamide-associated chemicals and indicated putative mechanisms of toxicity in the cells. These findings reveal that the increasing use of polyamide microplastics may pose a potential health risk for the exposed individuals, and it merits more attention.
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| 6. |
- Katsogiannos, Petros, et al.
(författare)
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Rapid changes in neuroendocrine regulation may contribute to reversal of type 2 diabetes after gastric bypass surgery
- 2020
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Ingår i: Endocrine. - : SPRINGER. - 1355-008X .- 1559-0100. ; 67:2, s. 344-353
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore the role of hormones and the autonomic nervous system in the rapid remission of diabetes after Roux-en-Y Gastric Bypass (RYGB).Research design and methods: Nineteen obese patients with type 2 diabetes, 7 M/12 F, were randomized (2:1) to RYGB or standard-of-care medical treatment (control). At baseline and 4 and 24 weeks post surgery, fasting blood sampling, OGTT, intravenous arginine challenge, and heart-rate variability (HRV) assessments were performed.Results: At both 4 and 24 weeks post-RYGB the following effects were found: arginine-stimulated insulin secretion was reduced. GLP-1, GIP, and glucagon rise during OGTT was enhanced. IGF-1 and GH levels increased. In addition, total HRV and spectral components P-LF (power of low frequency) and P-HF (power of high frequency) increased. At 4 weeks, morning cortisol was lower than baseline and 24 weeks. At 24 weeks, NEFA levels during OGTT, and the P-LF/P-HF ratio decreased. None of these changes were seen in the control group.Conclusions: There were rapid changes within 4 weeks after RYGB: signs of enhanced parasympathetic nerve activity, reduced morning cortisol, and enhanced incretin and glucagon responses to glucose. The findings suggest that neurohormonal mechanisms can contribute to the rapid improvement of insulin resistance and glycemia following RYGB in type 2 diabetes.
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| 7. |
- Ulfenborg, Benjamin, 1985-, et al.
(författare)
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Multi-Assignment Clustering : Machine learning from a biological perspective
- 2021
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Ingår i: Journal of Biotechnology. - : Elsevier. - 0168-1656 .- 1873-4863. ; 326, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- A common approach for analyzing large-scale molecular data is to cluster objects sharing similar characteristics. This assumes that genes with highly similar expression profiles are likely participating in a common molecular process. Biological systems are extremely complex and challenging to understand, with proteins having multiple functions that sometimes need to be activated or expressed in a time-dependent manner. Thus, the strategies applied for clustering of these molecules into groups are of key importance for translation of data to biologically interpretable findings. Here we implemented a multi-assignment clustering (MAsC) approach that allows molecules to be assigned to multiple clusters, rather than single ones as in commonly used clustering techniques. When applied to high-throughput transcriptomics data, MAsC increased power of the downstream pathway analysis and allowed identification of pathways with high biological relevance to the experimental setting and the biological systems studied. Multi-assignment clustering also reduced noise in the clustering partition by excluding genes with a low correlation to all of the resulting clusters. Together, these findings suggest that our methodology facilitates translation of large-scale molecular data into biological knowledge. The method is made available as an R package on GitLab (https://gitlab.com/wolftower/masc).
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| 8. |
- Valiente Bermejo, María Asunción, 1972-, et al.
(författare)
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Microstructure of laser metal deposited duplex stainless steel : Influence of shielding gas and heat treatment
- 2021
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Ingår i: Welding in the World. - : Springer. - 0043-2288 .- 1878-6669. ; 65, s. 525-541
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Tidskriftsartikel (refereegranskat)abstract
- This research work is the first step in evaluating the feasibility of producing industrial components by using Laser Metal Deposition with duplex stainless steel Wire (LMDw). The influence of Ar and N2 shielding gases was investigated in terms of nitrogen loss and in the microstructure and austenite content of different deposited geometries. The evolution of the microstructure in the build-up direction of the Ar and N2-shielded blocks was compared in the heat-treated and as-deposited conditions. The susceptibility for oxygen pick-up in the LMDw deposits was also analyzed, and oxygen was found to be in the range of conventional gas-shielded weldments. Nitrogen loss occurred when Ar-shielding was used; however, the use of N2-shielding prevented nitrogen loss. Austenite content was nearly doubled by using N2-shielding instead of Ar-shielding. The heat treatment resulted in an increase of the austenite content and of the homogeneity in the microstructure regardless of the shielding gas used. The similarity in microstructure and the low spread in the phase balance for the as-deposited geometries is a sign of having achieved a stable and consistent LMDw process in order to proceed with the build-up of more complex geometries closer to industrial full-size components.
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