| id |
dc6b1283-ca23-42d1-9c37-b909b09b9b5f |
| user_id |
8684964a-bab1-4235-93a8-5fd5e24a1d0a |
| job_id |
fkjaceic-2926 |
| base_model_name |
xevyo |
| base_model_path |
/home/sid/tuning/finetune/backend/output/xevyo-bas /home/sid/tuning/finetune/backend/output/xevyo-base-v1/merged_fp16_hf... |
| model_name |
The role of polyamines i |
| model_desc |
The role of polyamines in protein-dependent |
| model_path |
/home/sid/tuning/finetune/backend/output/fkjaceic- /home/sid/tuning/finetune/backend/output/fkjaceic-2926/merged_fp16_hf... |
| source_model_name |
xevyo |
| source_model_path |
/home/sid/tuning/finetune/backend/output/xevyo-bas /home/sid/tuning/finetune/backend/output/xevyo-base-v1/merged_fp16_hf... |
| source_job_id |
xevyo-base-v1 |
| dataset_desc |
“The Role of Polyamines in Protein-Dependent Hypox “The Role of Polyamines in Protein-Dependent Hypoxic Tolerance of Drosophila” is a research article that investigates why dietary proteins and amino acids drastically reduce survival under chronic low-oxygen conditions (hypoxia), using Drosophila melanogaster as the model organism. The study reveals a surprising and biologically important mechanism linking amino acids, polyamines, and hypoxic stress tolerance.
Core Finding
Under chronic hypoxia (5% oxygen), even small amounts of dietary protein dramatically shorten the lifespan of adult flies. This effect is not seen under normal oxygen. The researchers discovered that this life-shortening effect is driven by:
Amino acids themselves
Their metabolic intermediates (L-ornithine, L-citrulline)
Polyamines (putrescine, spermidine, spermine)
Every natural amino acid tested decreased fly survival under hypoxia, even at low millimolar concentrations.
The role of polyamines in prote…
Why proteins become toxic in hypoxia
The study shows that chronic hypoxia unmasks a harmful effect of amino acid metabolism:
Amino acids feed into the polyamine synthesis pathway.
Polyamines, in turn, promote hypusination of eIF5A, a unique post-translational modification required for the active form of this protein.
Both polyamines and eIF5A hypusination are shown to reduce hypoxic tolerance and shorten lifespan.
The role of polyamines in prote…
Thus, amino acids → polyamines → eIF5A hypusination → reduced hypoxic survival.
Pharmacological evidence
Two inhibitors were used to dissect the mechanism:
DFMO, an inhibitor of ornithine decarboxylase (the first enzyme in polyamine synthesis), partially protected hypoxic flies from amino-acid toxicity but had no effect against polyamines themselves. This shows that polyamines are downstream of amino acids.
The role of polyamines in prote…
GC7, a potent inhibitor of eIF5A hypusination, partially rescued flies from both amino-acid- and polyamine-induced death. This demonstrates that eIF5A activation is a key step linking amino acids to reduced hypoxic tolerance.
The role of polyamines in prote…
Hypoxia-inducible factor (HIF-1α/Sima)
The authors investigated whether the classic hypoxia-response pathway played a role. They found:
Chronic hypoxia did not activate strong HIF-1α signalling in adult flies.
Loss-of-function mutants for sima (Drosophila HIF-1α) still showed the same amino-acid toxicity.
The role of polyamines in prote…
Thus, the mechanism is independent of HIF-1α, and represents a separate amino-acid sensing pathway.
Broader biological significance
The study provides strong evidence that:
Low-protein diets dramatically improve hypoxic tolerance, while proteins—through amino acids and polyamines—make tissues more vulnerable during oxygen shortage.
These mechanisms likely have parallels in mammals, where polyamine levels rise in ischemic conditions (stroke, myocardial infarction).
The role of polyamines in prote…
This suggests potential therapeutic strategies: targeting polyamine synthesis or eIF5A hypusination to improve survival under ischemic or hypoxic stress.
Conclusion
The paper identifies a previously unknown mechanism by which dietary amino acids reduce survival under chronic hypoxia. The key pathway is:
Amino acids → polyamine synthesis → eIF5A hypusination → reduced hypoxic tolerance
This mechanism explains why low-protein diets increase hypoxic survival and opens possibilities for treatments against hypoxia-related diseases.... |
| dataset_meta |
{"num_examples": 162, "bad_lines": {"num_examples": 162, "bad_lines": 0}... |
| dataset_path |
/home/sid/tuning/finetune/backend/output/fkjaceic- /home/sid/tuning/finetune/backend/output/fkjaceic-2926/data/fkjaceic-2926.json... |
| training_output |
null |
| status |
completed |
| created_at |
1764398087 |
| updated_at |
1764398447 |
| source_adapter_path |
NULL |
| adapter_path |
/home/sid/tuning/finetune/backend/output/fkjaceic- /home/sid/tuning/finetune/backend/output/fkjaceic-2926/adapter... |
| plugged_in |
False |