Investigation of Ring Finger Protein 8 in Mammalian Physiology and Pathogenesis
Bibliographic record
Abstract
While genomic stability is often viewed as a cellular shield against malignant transformation, DNA double-strand breaks (DSBs) are probably the most dangerous threat to the maintenance of a stable cellular genome. Mammalian cells have evolved a sophisticated DNA damage response (DDR) network that senses the physical existence of DNA DSBs, followed by signal propagation to repair these genetic lesions. Interestingly, DSBs are not only hazardous, but are also programmed to occur during normal physiological processes such as immunoglobulin heavy chain (IgH) class switch recombination (CSR), an important mechanism for antibody diversification and specification of immunoglobulin effector function during a humoral immune response in mammals. Through catalyzing ubiquitylation of the H2A-type histones flanking DNA DSBs, the E3 ligase Ring finger protein 8 (Rnf8) orchestrates the assembly of components of homologous recombination (HR) and nonhomologous end joining (NHEJ) repair machineries into DSB-induced foci. To examine the in vivo functions of Rnf8 during mammalian development and determine the effects of its deficiency on the development of various diseases, we generated Rnf8 knockout mouse models and elucidated the pleiotropic in vivo functions of Rnf8. Overall, this thesis highlights the physiological significance of Rnf8 in shielding against DNA DSB repair defects, genomic instability, male infertility, immunodeficiency and cancer development at the organism level.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
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".