| 1. |
- Gõmez-Elvira, Javier, et al.
(författare)
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Curiosity's rover environmental monitoring station : Overview of the first 100 sols
- 2014
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Ingår i: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:7, s. 1680-1688
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Tidskriftsartikel (refereegranskat)abstract
- In the first 100 Martian solar days (sols) of the Mars Science Laboratory mission, the Rover Environmental Monitoring Station (REMS) measured the seasonally evolving diurnal cycles of ultraviolet radiation, atmospheric pressure, air temperature, ground temperature, relative humidity, and wind within Gale Crater on Mars. As an introduction to several REMS-based articles in this issue, we provide an overview of the design and performance of the REMS sensors and discuss our approach to mitigating some of the difficulties we encountered following landing, including the loss of one of the two wind sensors. We discuss the REMS data set in the context of other Mars Science Laboratory instruments and observations and describe how an enhanced observing strategy greatly increased the amount of REMS data returned in the first 100 sols, providing complete coverage of the diurnal cycle every 4 to 6 sols. Finally, we provide a brief overview of key science results from the first 100 sols. We found Gale to be very dry, never reaching saturation relative humidities, subject to larger diurnal surface pressure variations than seen by any previous lander on Mars, air temperatures consistent with model predictions and abundant short timescale variability, and surface temperatures responsive to changes in surface properties and suggestive of subsurface layering. Key Points Introduction to the REMS results on MSL mission Overiview of the sensor information Overview of operational constraints
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| 2. |
- Esteller, Manel, et al.
(författare)
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DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis
- 2001
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 10:26, s. 3001-3007
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Tidskriftsartikel (refereegranskat)abstract
- Cancer cells have aberrant patterns of DNA methylation including hypermethylation of gene promoter CpG islands and global demethylation of the genome. Genes that cause familial cancer, as well as other genes, can be silenced by promoter hypermethylation in sporadic tumors, but the methylation of these genes in tumors from kindreds with inherited cancer syndromes has not been well characterized. Here, we examine CpG island methylation of 10 genes (hMLH1, BRCA1, APC, LKB1, CDH1, p16(INK4a), p14(ARF), MGMT, GSTP1 and RARbeta2) and 5-methylcytosine DNA content, in inherited (n = 342) and non-inherited (n = 215) breast and colorectal cancers. Our results show that singly retained alleles of germline mutated genes are never hypermethylated in inherited tumors. However, this epigenetic change is a frequent second "hit", associated with the wild-type copy of these genes in inherited tumors where both alleles are retained. Global hypomethylation was similar between sporadic and hereditary cases, but distinct differences existed in patterns of methylation at non-familial genes. This study demonstrates that hereditary cancers "mimic" the DNA methylation patterns present in the sporadic tumors.
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| 3. |
- Párraga, Alba Atienza, 1988-
(författare)
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The Epigenome of Multiple Myeloma : From genome-wide analysis to pharmacological manipulation
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nowadays epigenetic dysregulation is known to play a crucial role in virtually all cancers. In multiple myeloma (MM), an extensively heterogeneous malignancy, the key common feature among patients is the gene silencing imposed by the PRC2 complex through the addition of H3K27me3. This thesis focuses on the exploration of the MM epigenomic landscape, with an emphasis on both the interplay between H3K27me3 and other epigenetic tags, and on the effects of a series of inhibitors altering this profile.In paper I we provide the genome-wide H3K27me3 distribution unique to MM and demonstrate that the silencing of genes in the profile correlates with an advanced and poor-outcome disease. Reduction of H3K27me3 using the EZH2 inhibitor UNC1999 reactivates genes with anti-tumor activity and induces apoptosis in vitro.EZH2 inhibition also leads to downregulation of the MM oncogenes IRF-4, BLIMP-1, XBP-1 and c-MYC. Paper II identifies miR-125a-3p and miR-320c, predicted to target these oncogenes, as part of the PRC2 targets induced upon treatment.In addition, H3K27me3 can be recognized and bound by the PRC1 complex. In paper III we show that inhibition of PRC1 using PTC-209 induces apoptosis and this is further enhanced when PTC-209 is combined with UNC1999. Moreover, PTC-209 has been previously shown to reduce the expression of c-MYC. Combined treatment using PTC-209 and JQ1, demonstrated to downregulate c-MYC, results in additive and synergistic effects in reducing MM cell viability.In paper IV we present the first catalogue of genomic regulatory regions in normal plasma cells, as predicted by their combinations of histone marks. Using this, we demonstrate that in MM a subset of TSSs and enhancers become targeted by H3K27me3 and display high DNA methylation, pointing towards a possible silencing. Conversely, poised TSSs lose H3K27me3 and seemingly become de novo activated. Furthermore, we show that EZH2 physically interacts with the DNA methyltransferase DNMT1 and that combined inhibition using UNC1999 and the DNA hypomethylating agent AZA blocks the G2/M arrest triggered by AZA and induces apoptosis.In summary, this thesis highlights the complex interconnectivity of epigenetic mechanisms in MM and provides proof-of-principle of the anti-MM effects derived from inhibiting epigenetic components in single or combinatorial regimens.
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