Bibliographic record
Abstract
Introduction Most eukaryotic cells rely on ATP produced by oxidative phosphorylation for their normal function. This process requires the activity of five multisubunit enzyme complexes located in the inner mitochondrial membrane. Electron transport along complexes I-IV of the respiratory chain creates an electrochemical gradient for protons, which is used to drive the synthesis of ATP from ADP and inorganic phosphate by complex V, ATP synthetase. These multimeric complexes are unique in the cell in that the component polypeptide subunits are encoded by both the nuclear and mitochondrial (mtDNA) genomes. Of the approximately 80 structural subunits of oxidative phosphorylation, 13 are mtDNA-encoded, and all are essential for function. It has long been established that mtDNA is maternally inherited in mammals (Giles et al., 1980). As mitochondria are not made de novo, but rather only elaborated from other mitochondria, all of our mitochondria ultimately derive from those in one of our mother's oocytes. Paternal mitochondria containing mtDNA are present in the early embryo; however, they are rapidly degraded by a process that remains poorly understood. Mutations in mtDNA in humans are an important cause of a group of multisystem disorders usually referred to as mitochondrial encephalomyopathies because of the prominent involvement of the nervous system and striated muscle (Wallace, 1999; Schon, 2000; DiMauro and Schon, 2001). The minimum prevalence of these disorders has been estimated at about 1:8000 in a Caucasian population in northern England (Chinnery et al., 2000a). The rules governing the transmission and segregation of mtDNA in the female germline have thus taken on a renewed importance for genetic counselling and the clinical management of patients affected by these disorders. Further, the introduction of new reproductive technologies, such as cytoplasmic transfer, direct intracytoplasmic sperm injection (ICSI) and animal cloning, have forced a re-evaluation of the potential contribution of exogenous or paternally derived mitochondria to the next generation. In this chapter, the current knowledge in these areas will be reviewed. Mitochondrial DNA: structure, replication and expression The mtDNA of all mammals investigated has the same basic structure: a double-stranded circular DNA molecule of ∼16.5 kilobases (kb) (Figure 14.1). The two strands are referred to as heavy (H) and light (L) reflecting their behaviour in caesium chloride (CsCl) density gradients.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.004 |
| Scholarly communication | 0.003 | 0.004 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.014 | 0.007 |
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".