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- Fornes, R., et al.
(author)
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The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams
- 2017
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Journal article (peer-reviewed)abstract
- Pregnant women with polycystic ovary syndrome (PCOS) are often overweight or obese. To study the effects of maternal androgen excess in obese dams on metabolism, placental function and fetal growth, female C57Bl6J mice were fed a control (CD) or a high fat/high sucrose (HF/HS) diet for 4-10 weeks, and then mated. On gestational day (GD) 15.5-17.5, dams were injected with dihydrotestosterone (CD-DHT, HF/HS-DHT) or a vehicle (CD-Veh, HF/HS-Veh). HF/HS dams had higher fat content, both before mating and on GD18.5, with no difference in glucose homeostasis, whereas the insulin sensitivity was higher in DHT-exposed dams. Compared to the CD groups, the livers from HF/HS dams weighed more on GD18.5, the triglyceride content was higher, and there was a dysregulation of liver enzymes related to lipogenesis and higher mRNA expression of Fitm1. Fetuses from HF/HS-Veh dams had lower liver triglyceride content and mRNA expression of Srebf1c. Maternal DHT exposure, regardless of diet, decreased fetal liver Pparg mRNA expression and increased placental androgen receptor protein expression. Maternal diet-induced obesity, together with androgen excess, affects maternal and fetal liver function as demonstrated by increased triglyceride content and dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage.
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| 2. |
- Larsson, S., et al.
(author)
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Simple method for quality factor estimation in resonating MEMS structures
- 2018
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In: Proceedings of the 17th International Conference on Micro and Nanotechnology for Power Generation and Energy Conversion Applications, 2017. - : IOP Publishing.
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Conference paper (peer-reviewed)abstract
- The quality factor of a packaged MEMS resonating structure depends on both the packaging pressure and the structure's proximity to the walls. This type of mechanical constraints, which causes energy dissipation from the structure to the surrounding air, are applicable for oscillating energy harvesters and should be considered in the design process. However, the modelling of energy losses or the measurements of their direct influence inside a packaged chip is not trivial. In this paper, a simple experimental method to quantify the energy loss in an oscillating MEMS structures due to the surrounding air is described together with preliminary results. The main advantage of the method is the ability to characterize the damping contributions under different vacuum and packaging conditions without requiring any packaging of the harvester chip or fabrication of multiple devices with different cavity depths. © Published under licence by IOP Publishing Ltd.
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| 3. |
- Levin, A., et al.
(author)
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Novel insights into the disease transcriptome of human diabetic glomeruli and tubulointerstitium
- 2020
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In: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 35:12, s. 2059-2072
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Journal article (peer-reviewed)abstract
- Background. Diabetic nephropathy (DN) is the most common cause of end-stage renal disease, affecting similar to 30% of the rapidly growing diabetic population, and strongly associated with cardiovascular risk. Despite this, the molecular mechanisms of disease remain unknown. Methods. RNA sequencing (RNAseq) was performed on paired, micro-dissected glomerular and tubulointerstitial tissue from patients diagnosed with DN [n = 19, 15 males, median (range) age: 61 (30-85) years, chronic kidney disease stages 1-4] and living kidney donors [n = 20, 12 males, median (range) age: 56 (30-70) years]. Results. Principal component analysis showed a clear separation between glomeruli and tubulointerstitium transcriptomes. Differential expression analysis identified 1550 and 4530 differentially expressed genes, respectively (adjusted P < 0.01). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses highlighted activation of inflammation and extracellular matrix (ECM) organization pathways in glomeruli, and immune and apoptosis pathways in tubulointerstitium of DN patients. Specific gene modules were associated with renal function in weighted gene co-expression network analysis. Increased messengerRNA (mRNA) expression of renal damage markers lipocalin 2 (LCN) and hepatitis A virus cellular receptor1 (HAVCR1) in the tubulointerstitial fraction was observed alongside higher urinary concentrations of the corresponding proteins neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in DN patients. Conclusions. Here we present the first RNAseq experiment performed on paired glomerular and tubulointerstitial samples from DN patients. We show that prominent disease-specific changes occur in both compartments, including relevant cellular processes such as reorganization of ECM and inflammation (glomeruli) as well as apoptosis (tubulointerstitium). The results emphasize the potential of utilizing high-throughput transcriptomics to decipher disease pathways and treatment targets in this high-risk patient population.
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