| 1. |
- Vizoso, Miguel, et al.
(författare)
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Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR
- 2015
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 21:7, s. 741-
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Tidskriftsartikel (refereegranskat)abstract
- Metastasis is responsible for most cancer-related deaths, and, among common tumor types, melanoma is one with great potential to metastasize. Here we study the contribution of epigenetic changes to the dissemination process by analyzing the changes that occur at the DNA methylation level between primary cancer cells and metastases. We found a hypomethylation event that reactivates a cryptic transcript of the Rab GTPase activating protein TBC1D16 (TBC1D16-47 kDa; referred to hereafter as TBC1D16-47KD) to be a characteristic feature of the metastatic cascade. This short isoform of TBC1D16 exacerbates melanoma growth and metastasis both in vitro and in vivo. By combining immunoprecipitation and mass spectrometry, we identified RAB5C as a new TBC1D16 target and showed that it regulates EGFR in melanoma cells. We also found that epigenetic reactivation of TBC1D16-47KD is associated with poor clinical outcome in melanoma, while conferring greater sensitivity to BRAF and MEK inhibitors.
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| 2. |
- Peris-Frau, Patricia, et al.
(författare)
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Comparative evaluation of DNA integrity using sperm chromatin structure assay and Sperm-Ovis-Halomax during in vitro capacitation of cryopreserved ram spermatozoa
- 2019
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Ingår i: Reproduction in domestic animals. - : WILEY. - 0936-6768 .- 1439-0531. ; 54, s. 46-49
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to compare the ability of sperm chromatin structure assay (SCSA (R)) and Sperm-Ovis-Halomax (R) to detect DNA fragmentation in frozen-thawed ram spermatozoa incubated under capacitating conditions in synthetic oviductal fluid (SOF) supplemented with oestrous sheep serum (SOF-ESS) at multiple time points (0-240 min). Incubation in SOF-ESS had no significant effects on SCSA (R) parameters while the percentage of spermatozoa with fragmented DNA measured by Sperm-Ovis-Halomax (R) increased after 180 min of incubation. In addition, no correlation or agreement was found between the techniques, suggesting that SCSA (R) and Sperm-Ovis-Halomax (R) may quantify different types of DNA damage in ram spermatozoa under these experimental conditions.
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| 3. |
- Peris-Frau, Patricia, et al.
(författare)
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Unravelling how in vitro capacitation alters ram sperm chromatin before and after cryopreservation
- 2021
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Ingår i: Andrology. - : WILEY. - 2047-2919 .- 2047-2927. ; 9:1, s. 414-425
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Tidskriftsartikel (refereegranskat)abstract
- Background Sperm chromatin structure provides valuable information for the prediction of male fertility and can be altered during different procedures. Previous studies have shown that sperm chromatin condensation decreased during in vitro capacitation. Moreover, cryopreservation can affect sperm DNA integrity and chromatin compaction. Objectives This study aimed to investigate dynamic modifications produced in the chromatin structure of ram spermatozoa during in vitro capacitation before and after cryopreservation. Materials and methods Chromatin decondensation (AB+), DNA methylation, DNA fragmentation index (%DFI) and high DNA stainability (HDS) were evaluated in fresh and frozen-thawed ram spermatozoa incubated under capacitating (CAP) conditions at 1, 5, 15, 30, 60, 120, 180 and 240 minutes and under non-capacitating (NC) conditions at 0, 15 and 240 minutes. Results Incubation in NC conditions did not induce significant changes in chromatin condensation (P > .05; AB + and HDS). However, incubation of fresh and cryopreserved ram spermatozoa under CAP conditions significantly increased chromatin decondensation (P < .05), reaching the highest percentage of AB + and HDS from 180 to 240 minutes in fresh samples and from 5 to 30 minutes in cryopreserved samples. Both variables (HDS and AB+) were positively correlated with tyrosine phosphorylation, total motility, progressive motility, curvilinear velocity and amplitude of lateral head displacement, as well as between them under CAP conditions in fresh and cryopreserved spermatozoa. DNA methylation significantly increased in cryopreserved spermatozoa (P < .05), but only after extended incubation under CAP conditions (60-240 minutes), while the %DFI, albeit higher in cryopreserved samples, remained constant under CAP and NC conditions in both types of sample (P > .05). Discussion and conclusions Our results suggest that sperm chromatin condensation decreased progressively during in vitro capacitation of ram spermatozoa, while sperm DNA integrity remained intact. Such changes in chromatin condensation appeared faster after sperm cryopreservation.
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| 4. |
- Suarez, David Orozco, et al.
(författare)
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CMAG : A Mission to Study and Monitor the Inner Corona Magnetic Field
- 2023
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Ingår i: Aerospace. - 2226-4310. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- Measuring magnetic fields in the inner corona, the interface between the solar chromosphere and outer corona, is of paramount importance if we aim to understand the energetic transformations taking place there, and because it is at the origin of processes that lead to coronal heating, solar wind acceleration, and of most of the phenomena relevant to space weather. However, these measurements are more difficult than mere imaging because polarimetry requires differential photometry. The coronal magnetograph mission (CMAG) has been designed to map the vector magnetic field, line-of-sight velocities, and plane-of-the-sky velocities of the inner corona with unprecedented spatial and temporal resolutions from space. This will be achieved through full vector spectropolarimetric observations using a coronal magnetograph as the sole instrument on board a spacecraft, combined with an external occulter installed on another spacecraft. The two spacecraft will maintain a formation flight distance of 430 m for coronagraphic observations, which requires a 2.5 m occulter disk radius. The mission will be preferentially located at the Lagrangian L5 point, offering a significant advantage for solar physics and space weather research. Existing ground-based instruments face limitations such as atmospheric turbulence, solar scattered light, and long integration times when performing coronal magnetic field measurements. CMAG overcomes these limitations by performing spectropolarimetric measurements from space with an external occulter and high-image stability maintained over time. It achieves the necessary sensitivity and offers a spatial resolution of 2.5 '' and a temporal resolution of approximately one minute, in its nominal mode, covering the range from 1.02 solar radii to 2.5 radii. CMAG relies on proven European technologies and can be adapted to enhance any other solar mission, offering potential significant advancements in coronal physics and space weather modeling and monitoring.
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