| 1. |
- Cvjetkovic, Aleksander, et al.
(författare)
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Extracellular vesicles in motion
- 2017
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Ingår i: Science Matters. - : Sciencematters. - 2297-8240 .- 2297-9239.
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Tidskriftsartikel (refereegranskat)abstract
- By secreting extracellular vesicles (EVs), including exosomes and microvesicles, into the extracellular milieu, cells can convey complex biological messages between each other. These vesicles are generally thought to be static packages lacking the flexibility of their parental cells in terms of motility and the ability to change shape. However, cryo-electron micrographs reveal the presence of actin-like filaments in a subpopulation of EVs, raising the question if these vesicles could possess motile capabilities similar to that produced by actin in cells. We here show that fluorescently labeled EVs change their shape in a matter of minutes, regardless of whether they are isolated from human body fluids, mouse tissue or cell culture of human cells or yeast. Our findings therefore cast doubt on movement being confined to cells, suggesting that some EVs indeed have an intrinsic capacity to move. This novel observation showing morphological plasticity among EVs adds another level of complexity to the already multifaceted vesicular secretome, and may lead to new ways in which we perceive these nano-carriers of intercellular signals.
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| 2. |
- Zabeo, Davide, 1992, et al.
(författare)
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3D ultrastructure of multi-vesicular bodies in fission yeast
- 2017
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Ingår i: Science Matters. - : Sciencematters. - 2297-8240 .- 2297-9239. ; 3:3
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Tidskriftsartikel (refereegranskat)abstract
- The multi-vesicular body (MVB) organelle and the cellular sorting pathway associated with it are very well characterized in budding yeast (Saccharomyces cerevisiae). However, little is known about MVB structure and function in fission yeast (Schizosaccharomyces pombe). In this work, we investigated and characterized the three-dimensional ultrastructure of MVBs in S. pombe using electron tomography. We discovered a positive correlation between MVB size and the number of intralumenal vesicles (ILVs) contained in them. MVBs grew larger with the progression of the cell cycle, hinting at an unknown interaction between the regulation of the two processes. Larger MVBs were also observed in the temperature-sensitive cdc25-22 mutant, which is defective in cell cycle progression into mitosis at the restrictive temperature. This study offers, to our knowledge, the first electron microscopic observation and tomographic reconstruction of MVBs in S. pombe.
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| 3. |
- Cantù, Claudio, et al.
(författare)
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Unexpected survival of mice carrying a mutation in Pygo2 that strongly reduces its binding to Bcl9/9l
- 2016
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Ingår i: Matters Select. - Zürich : ScienceMatters AG. - 2297-9239.
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Tidskriftsartikel (refereegranskat)abstract
- Pygopus is a transcriptional activator important for the Wnt signaling pathway. It binds to the beta-catenin transcriptional complex via the adaptor proteins Bcl9 and Bcl9l (Bcl9/9l). This complex is considered to be a suitable target for the treatment of tumors that display activated Wnt signaling. In the mouse, there are two Pygopus-encoding genes, Pygo1 and Pygo2 (Pygo1/2), with the latter playing a major role. Here we introduce a single amino acid substitution in Pygo2, which was previously shown to abrogate binding to Bcl9/9l, and cause lethality in Drosophila melanogaster. We confirm that mutant Pygo2 protein fails in interacting with Bcl9 but, unexpectedly, homozygous mice with this mutation are viable and fertile, even when this mutant allele is combined with a null mutation of the potentially redundant Pygo1. Based on this observation, we conjecture that the Pygo-Bcl9/9l interaction requires scant affinity in vivo to fulfill developmental functions and thrust forward the notion that this interaction surface could be targeted in cancer therapy without major consequences on homeostatic functions.
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| 4. |
- Turner, Russell T, et al.
(författare)
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Effects of a Four-day Spaceflight and Recombinant Human Growth Hormone on Cancellous Bone Microarchitecture in Femoral Head of Rapidly Growing Male Rats
- 2019
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Ingår i: Matters Select. - : Sciencematters. - 2297-9239.
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Tidskriftsartikel (refereegranskat)abstract
- Spaceflight results in reduced bone accrual and muscle atrophy in growing rodents. Some studies suggest that the detrimental effects of spaceflight are due, in part, to impaired growth hormone (GH) signaling. An experiment flown aboard STS-41 (October 6–10, 1990) evaluated the efficacy of recombinant human growth hormone (rhGH) in ameliorating the detrimental effects of spaceflight on the musculoskeletal system in male Sprague Dawley rats. The rats were 39 days old at launch and sacrificed following the 4–day flight. Ground controls (n=11/treatment group) and flight animals (n=8/treatment group) were treated with rhGH or excipient delivered using osmotic pumps implanted subcutaneously one day prior to launch. For the present examination, cancellous bone in the femoral head was evaluated using X-ray microtomography (microcomputed tomography), a technology not available when the study was performed. Spaceflight resulted in lower cancellous bone volume fraction, connectivity density, trabecular thickness and trabecular number, and higher trabecular separation. rhGH had no independent effect on cancellous bone architecture and there were no spaceflight by rhGH interactions. These findings suggest that a short interval of microgravity during rapid growth was sufficient to reduce accrual of cancellous bone and alter bone microarchitecture at an important weight bearing skeletal site. Additionally, increasing growth hormone levels was ineffective in preventing cancellous osteopenia in flight animals and did not increase cancellous bone volume fraction in ground controls.
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