| 1. |
- Gjorgjieva, Tamara, et al.
(författare)
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Loss of beta-Actin Leads to Accelerated Mineralization and Dysregulation of Osteoblast-Differentiation Genes during Osteogenic Reprogramming
- 2020
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Ingår i: Advanced Science. - : Wiley. - 2198-3844. ; 7:23
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Tidskriftsartikel (refereegranskat)abstract
- Actin plays fundamental roles in both the cytoplasm and the cell nucleus. In the nucleus, beta-actin regulates neuronal reprogramming by consolidating a heterochromatin landscape required for transcription of neuronal gene programs, yet it remains unknown whether it has a role in other differentiation models. To explore the potential roles of beta-actin in osteogenesis, beta-actin wild-type (WT) and beta-actin knockout (KO) mouse embryonic fibroblasts (MEFs) are reprogrammed to osteoblast-like cells using small molecules in vitro. It is discovered that loss of beta-actin leads to an accelerated mineralization phenotype (hypermineralization), accompanied with enhanced formation of extracellular hydroxyapatite microcrystals, which originate in the mitochondria in the form of microgranules. This phenotype is a consequence of rapid upregulation of mitochondrial genes including those involved in oxidative phosphorylation (OXPHOS) in reprogrammed KO cells. It is further found that osteogenic gene programs are differentially regulated between WT and KO cells, with clusters of genes exhibiting different temporal expression patterns. A novel function for beta-actin in osteogenic reprogramming through a mitochondria-based mechanism that controls cell-mediated mineralization is proposed.
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| 2. |
- Manenti, Laura, et al.
(författare)
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Search for dark photons using a multilayer dielectric haloscope equipped with a single-photon avalanche diode
- 2022
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Ingår i: Physical Review D. - : American Physical Society (APS). - 2470-0010 .- 2470-0029. ; 105:5
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of the search for dark photons with mass around 1.5 eV/c(2) using a multilayer dielectric haloscope equipped with an affordable and commercially available photosensor. The multilayer stack, which enables the conversion of dark photons (DP) to Standard Model photons, is made of 23 bilayers of alternating SiO2 and Si3N4 thin films with linearly increasing thicknesses through the stack (a configuration known as a "chirped stack"). The thicknesses have been chosen according to an optimization algorithm in order to maximize the DP-photon conversion in the energy region where the photosensor sensitivity peaks. This prototype experiment, dubbed "MuDHI" (Multilayer Dielectric Haloscope Investigation) by the authors of this paper, has been designed, developed, and run at the Astroparticle Laboratory of New York University Abu Dhabi, which marks the first time a dark matter experiment has been operated in the Middle East. No significant signal excess is observed, and the method of maximum log likelihood is used to set exclusion limits at 90% confidence level on the kinetic mixing coupling constant between dark photons and ordinary photons.
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| 3. |
- Venit, Tomas, et al.
(författare)
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Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic reprogramming is one of the hallmarks of tumorigenesis. Here, we show that nuclear myosin 1 (NM1) serves as a key regulator of cellular metabolism. NM1 directly affects mitochondrial oxidative phosphorylation (OXPHOS) by regulating mitochondrial transcription factors TFAM and PGC1α, and its deletion leads to underdeveloped mitochondria inner cristae and mitochondrial redistribution within the cell. These changes are associated with reduced OXPHOS gene expression, decreased mitochondrial DNA copy number, and deregulated mitochondrial dynamics, which lead to metabolic reprogramming of NM1 KO cells from OXPHOS to aerobic glycolysis.This, in turn, is associated with a metabolomic profile typical for cancer cells, namely increased amino acid-, fatty acid-, and sugar metabolism, and increased glucose uptake, lactate production, and intracellular acidity. NM1 KO cells form solid tumors in a mouse model, suggesting that the metabolic switch towards aerobic glycolysis provides a sufficient carcinogenic signal. We suggest that NM1 plays a role as a tumor suppressor and that NM1 depletion may contribute to the Warburg effect at the onset of tumorigenesis.
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