271 research outputs found
The heavy ion composition in 3HE-rich solar flares
The 3He-rich flares show a tendency to be enriched in heavy ions, and that this enrichment covers the charge range through Fe. The discovery of this association was responsible, in part, for the discarding of 3He enrichment models which involved spallation or thermonuclear reactions, since such models were unable to produce heavy nuclei enhancement. Results of a survey of heavy nucleus abundances observed in 66 3He-rich flares which occurred over the period October 1978 to June 1982 are presented
The heavy ion compositional signature in 3He-rich solar particle events
A survey of the approx. 1 MeV/nucleon heavy ion abundances in 66 He3-rich solar particle events was performed using the Max-Planck-Institut/University of Maryland and Goddard Space Flight Center instruments on the ISEE-3 spacecraft. The observations were carried out in interplanetary space over the period 1978 October through 1982 June. Earlier observations were confirmed which show an enrichment of heavy ions in HE3-rich events, relative to the average solar energetic particle composition in large particle events. For the survey near 1.5 MeV/nucleon the enrichments compared to large solar particle events are approximately He4:C:O:Ne:Mg:Si:Fe = 0.44:0.66:1.:3.4:3.5:4.1:9.6. Surprising new results emerging from the present broad survey are that the heavy ion enrichment pattern is the same within a factor of approx. 2 for almost all cases, and the degree of heavy ion enrichment is uncorrelated with the He3 enrichment. Overall, the features established appear to be best explained by an acceleration mechanism in which the He3 enrichment process is not responsible for the heavy ion enrichment, but rather the heavy ion enrichment is a measure of the ambient coronal composition at the sites where the He3-rich events occur
Statistical characterisation of full-disk EUV/XUV solar irradiance and correlation with solar activity
We investigate the distribution of fluctuations in solar irradiance when
integrated over the full disk, obtained using extreme ultraviolet/soft X-ray
observations from the SOHO CELIAS/SEM instrument. This time series sums over
both the contributions of single distinguishable flares, and of many other
processes. By detrending we select events with timescales of less than a few
hours such as waves, slow flows, and CMEs. The statistics generated by this
range of phenomena can be characterised by power-law-tailed distributions. We
show that (i) during the high-activity period 2000 Jan-June the tail exponent
a(T)=1.5 +/- 0.1; (ii) during the low-activity period 1996 Jan-June a(T)=3.0
+/- 0.2; and (iii) in general a(T) decreases with increasing activity.Comment: 4 pages, 5 figures; v.2 R-squared goodness of fits adde
TERT promoter mutation and aberrant hypermethylation are associated with elevated expression in medulloblastoma and characterise the majority of non-infant SHH subgroup tumours.
Validation of the MethylationEPIC BeadChip for fresh-frozen and formalin-fixed paraffin-embedded tumours
Active medulloblastoma enhancers reveal subgroup-specific cellular origins
Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Here, using H3K27ac and BRD4 chromatin immunoprecipitation followed by sequencing (ChIP-seq) coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-seq, that is responsible for subgroup divergence, and implicates candidate cells of origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins
Medulloblastoma and ependymoma cells display levels of 5-carboxylcytosine and elevated TET1 expression
Background
Alteration of DNA methylation (5-methylcytosine, 5mC) patterns represents one of the causes of tumorigenesis and cancer progression. Tet proteins can oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine (5caC). Although the roles of these oxidised forms of 5mC (oxi-mCs) in cancer pathogenesis are still largely unknown, there are indications that they may be involved in the mechanisms of malignant transformation. Thus, reduction of 5hmC content represents an epigenetic hallmark of human tumours and, according to our recent report; 5caC is enriched in a proportion of breast cancers and gliomas. Nevertheless, the distribution of oxi-mCs in paediatric brain tumours has not been assessed.
Findings
Here we analyse the global levels and spatial distribution of 5hmC and 5caC in 4 brain tumour cell lines derived from paediatric sonic hedgehog (SHH) pathway activated medulloblastomas (Daoy and UW228-3) and ependymomas (BXD-1425EPN and DKFZEP1NS). We show that, unlike HeLa cells, the paediatric tumour cell lines possess both 5hmC and 5caC at immunochemically detectable levels, and demonstrate that both modifications display high degrees of spatial overlap in the nuclei of medulloblastomas and ependymomas. Moreover, although 5hmC levels are comparable in the 4 brain tumour cell lines, 5caC staining intensities differ dramatically between them with highest levels of this mark in a subpopulation of DKFZ-EP1NS cells. Remarkably, the 5caC enrichment does not correlate with 5hmC levels and is not associated with alterations in Thymine DNA Glycosylase (TDG) expression in SHH medulloblastoma and ependymoma cell lines, but corresponds to elevated levels of TET1 transcript in UW228-3 and DKFZ-EP1NS cells.
Conclusions
We demonstrate that both 5caC enrichment and elevated TET1 expression are observed in SHH medulloblastomas and ependymomas. Our results suggest that increased Tet-dependent 5mC oxidation may represent one of the epigenetic signatures of cancers with neural stem cell origin and, thus, may contribute to development of novel approaches for diagnosis and therapy of the brain tumours
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