Characterization of astrocytes derived from fibroblasts of patients with amyotrophic lateral sclerosis
Bibliographic record
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular degenerative disease, targeting the motor neurons of the brain stem, motor cortex and spinal cord.Various lines of evidence have shown that glial cells contribute to disease development and progression.We derived astrocytes from fibroblasts of patients with familial ALS associated with SOD1 mutation and compared them to astrocytes derived from fibroblasts of age-and sex-matched controls.In order to assess astrocytic maturity, we compared the mRNA expression of astrocytic markers in astrocytes derived from three different protocols to that of human fetal astrocytes (HFA).Protocol 1 incorporated 10 weeks of astrogenesis.Protocol 2 incorporated 3 weeks of neurogenesis and 10 weeks of astrogenesis, and protocol 3 incorporated 2 weeks of astrogenesis.Our data show that astrocytes from all three protocols are similar in mRNA expression of astrocytic markers to HFA.However, morphologically, astrocytes from protocol 1 and 2 had astrocyte-like projections and therefore looked more like astrocytes compared to astrocytes from protocol 3. Next, we derived astrocytes from ALS patients, using protocol 2 and compared them to their age-and sexmatched controls.We found that the mRNA levels of EAAT2 and NESTIN were lower and the mRNA levels of glutamine synthetase, connexin43 and TGFB1 were higher in ALS astrocytes compared to their controls.Since the phenotypes observed in this study corroborate with previous literature exploring the role of astrocytes in ALS, these astrocytes may offer a system in which ALS can be studied in human cells.unconditional love and support through all the uncertainty and hardships that this career path brings.
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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) | 0.001 | 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".