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- Busti, Stefano, et al.
(författare)
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Respiratory metabolism and calorie restriction relieve persistent endoplasmic reticulum stress induced by calcium shortage in yeast
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 6, s. Art. no. 27942-
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Tidskriftsartikel (refereegranskat)abstract
- Calcium homeostasis is crucial to eukaryotic cell survival. By acting as an enzyme cofactor and a second messenger in several signal transduction pathways, the calcium ion controls many essential biological processes. Inside the endoplasmic reticulum (ER) calcium concentration is carefully regulated to safeguard the correct folding and processing of secretory proteins. By using the model organism Saccharomyces cerevisiae we show that calcium shortage leads to a slowdown of cell growth and metabolism. Accumulation of unfolded proteins within the calcium-depleted lumen of the endoplasmic reticulum (ER stress) triggers the unfolded protein response (UPR) and generates a state of oxidative stress that decreases cell viability. These effects are severe during growth on rapidly fermentable carbon sources and can be mitigated by decreasing the protein synthesis rate or by inducing cellular respiration. Calcium homeostasis, protein biosynthesis and the unfolded protein response are tightly intertwined and the consequences of facing calcium starvation are determined by whether cellular energy production is balanced with demands for anabolic functions. Our findings confirm that the connections linking disturbance of ER calcium equilibrium to ER stress and UPR signaling are evolutionary conserved and highlight the crucial role of metabolism in modulating the effects induced by calcium shortage.
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| 3. |
- Koochaki, Mohammad Sadegh, et al.
(författare)
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Facile strategy toward the development of a self-healing coating by electrospray method
- 2019
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Ingår i: Materials Research Express. - : Institute of Physics (IOP). - 2053-1591. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- A self-healing anti-corrosion epoxy coating was prepared by the incorporation of dual capsule healing system. Microcapsules were prepared through the facile electrospray method by using Poly(styrene-co-acrylonitrile) polymer as shell material. Polyetheramine and Methylene diphenyl diisocyanate (MDI) based isocyanate prepolymer were utilized as core materials because of their high reactivity and low sensitivity in forming polyurea polymers. Scanning electron microscopy (sem) images confirmed the spherical morphology of the prepared microcapsules with average diameters of 0.93 ± 0.55 μm and 1.21 ± 0.68 μm for the encapsulated polyetheramine and isocyanate microcapsules, respectively. Moreover, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA) results confirmed the successful encapsulation of both core materials with a high encapsulation yield (71% and 68% for Polyetheramine and MDI based isocyanate respectively). Electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization technique were used to assess the effects of utilizing the aforementioned system on the intrinsic anti-corrosion barrier property (on pristine samples ) and the self-healing efficiency (after cross scratching) of the resulting smart coatings. The corrosion assessment results confirmed the self-healing performance of the incorporated capsules along with a high healing efficiency (85%) for the optimum microcapsule content.
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| 4. |
- Macchi, Chiara, et al.
(författare)
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Leptin, Resistin, and Proprotein Convertase Subtilisin/Kexin Type 9 - The Role of STAT3
- 2020
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Ingår i: The American journal of pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 190:11, s. 2226-2236
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Tidskriftsartikel (refereegranskat)abstract
- In a condition of dysfunctional visceral fat depots, as in the case of obesity, alterations in adipokines levels may be detrimental for the cardiovascular system. The proinflammatory leptin and resistin adipokines have been described as possible links between obesity and atherosclerosis. The present study was aimed at evaluating whether proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein metabolism, is induced by leptin and resistin through the involvement of the inflammatory pathway of signal transducer and activator of transcript 3 (STAT3). In HepG2 cells, leptin and resistin upregulated PCSK9 gene and protein expression as well as the phosphorylation of STAT3. Upon STAT3 silencing, leptin and resistin lost their ability to activate PCSK9. The knock-down of STAT3 did not affect the expression of leptin and resistin receptors as well as that of PCSK9. The analysis of human PCSK9 promoter region showed that the two adipokines raise PCSK9 promoter activity via the involvement of sterol regulatory element motif. In healthy male, a positive association between circulating leptin and PCSK9 levels was found only when BMI was < 25 kg/m2. In conclusion, our study identified STAT3 as one of the molecular regulators of leptin- and resistin-mediated transcriptional induction of PCSK9.
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- Magni, Stefano, et al.
(författare)
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Inferring upstream regulatory genes of FOXP3 in human regulatory T cells from time-series transcriptomic data
- 2024
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Ingår i: npj Systems Biology and Applications. - : Springer Nature. - 2056-7189. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of upstream regulatory genes of a gene of interest still remains challenging. Here we applied a scalable computational method to unbiasedly predict candidate regulatory genes of critical transcription factors by searching the whole genome. We illustrated our approach with a case study on the master regulator FOXP3 of human primary regulatory T cells (Tregs). While target genes of FOXP3 have been identified, its upstream regulatory machinery still remains elusive. Our methodology selected five top-ranked candidates that were tested via proof-of-concept experiments. Following knockdown, three out of five candidates showed significant effects on the mRNA expression of FOXP3 across multiple donors. This provides insights into the regulatory mechanisms modulating FOXP3 transcriptional expression in Tregs. Overall, at the genome level this represents a high level of accuracy in predicting upstream regulatory genes of key genes of interest.
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