Bibliographic record
Abstract
Abstract Telomeres are found at chromosome ends. When these ends are not protected by telomeric capping, the telomeres are recognized as double-strand breaks and the consequent recruitment of DNA repair machinery may affect cellular fate. Furthermore, telomeric capping proteins have been shown to interact with some of the proteins involved in DNA repair. A direct link thus exists between DNA repair and telomeres. However, few data are available on the changes in telomere structure associated with the different modes of DNA repair. To study the effects of three DNA-damaging agents on telomere structure, we exposed normal human primary fibroblasts to H202, gamma radiation, or UVB rays. The cells were then harvested at different times over a period of 24 hours. First the telomere nuclear architecture was studied by quantitative fluorescence in situ hybridization with a telomere-specific peptide nucleic acid probe followed by 3D telomere imaging. H202 treatment induced a significant reduction of telomere signals and a disruption of the nuclear volume that became normal after 24 hours of recovery. Also, telomere positioning was positively correlated to nuclear volume that disrupted over time. For gamma irradiation, the nuclear volume was positively correlated to the number of telomere signals and negatively correlated to telomere average intensity for each time point. UVB lead to a significant formation of telomeric aggregates and disruption of telomere nuclear shape by forming ellipsoid instead of circular shape. Next, we studied the effects of these different DNA damage agents on the expression profile of telomere shelterin genes. The most affected genes were TRF1, POT1, TIN2 and Rap1. For instance, while the three agents showed a high induction of TIN2, gamma and H202 treatments presented high induction for POT1 and only H202 treatment induced significant increase of TRF1. In conclusion, certain DNA-damaging events alter telomere structure by acting on nuclear telomere architecture and the expression profile of some telomere shelterin genes. The disruption of telomere structure due to acute insults might have an influence on cell homeostasis and the pathways involved can shed light for a better understanding of some pathological and therapeutic processes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2996. doi:10.1158/1538-7445.AM2011-2996
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".