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IMF-091-03-0001-en	Why does an insertion or deletion not divisible by three disrupt the whole downstream protein?	The code is read as nonoverlapping triplets in a frame set at initiation, so such an indel shifts every downstream codon.	Integrated Medical Foundations; chapter 91, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: f4dfd75df2f98ac7d467cbbdb1662ec88233708ce622d926cd91a536d7e04f6c; editorial review pending	imf lang::en chapter::091 module::091-03 review::pending
IMF-091-03-0002-en	Why is the accuracy of aminoacyl-transfer-RNA synthetases crucial to translation fidelity?	The ribosome verifies codon-anticodon pairing but generally cannot assess amino acid identity, so a mischarged transfer RNA inserts the wrong residue; editing sites guard against this.	Integrated Medical Foundations; chapter 91, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: f4dfd75df2f98ac7d467cbbdb1662ec88233708ce622d926cd91a536d7e04f6c; editorial review pending	imf lang::en chapter::091 module::091-03 review::pending
IMF-091-03-0003-en	Why is the ribosome described as a ribozyme?	Peptide-bond formation in the large subunit is catalysed by ribosomal RNA rather than by ribosomal protein.	Integrated Medical Foundations; chapter 91, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: f4dfd75df2f98ac7d467cbbdb1662ec88233708ce622d926cd91a536d7e04f6c; editorial review pending	imf lang::en chapter::091 module::091-03 review::pending
IMF-091-03-0004-en	Which features regulate eukaryotic initiation, the rate-limiting stage of translation?	The small subunit is recruited at the cap and scans to an AUG in favourable context; upstream open reading frames, RNA structure, internal entry, cap accessibility and initiation-factor phosphorylation modulate this.	Integrated Medical Foundations; chapter 91, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: f4dfd75df2f98ac7d467cbbdb1662ec88233708ce622d926cd91a536d7e04f6c; editorial review pending	imf lang::en chapter::091 module::091-03 review::pending
IMF-091-03-0005-en	Why do cells suppress general translation during nutrient deficiency, viral infection or endoplasmic-reticulum stress, and how?	Translation is energetically costly, using ATP for activation and GTP for elongation, so cells phosphorylate initiation factors to suppress general initiation while selected stress transcripts continue.	Integrated Medical Foundations; chapter 91, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: f4dfd75df2f98ac7d467cbbdb1662ec88233708ce622d926cd91a536d7e04f6c; editorial review pending	imf lang::en chapter::091 module::091-03 review::pending
IMF-091-03-0006-en	How do mTORC1 and AMP-activated kinase balance protein synthesis, and what happens when the balance is lost?	mTORC1 promotes synthesis and suppresses autophagy when nutrients and energy suffice, while AMP-activated kinase restrains it at low energy; excess anabolism supports cancer, excess suppression contributes to wasting.	Integrated Medical Foundations; chapter 91, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: f4dfd75df2f98ac7d467cbbdb1662ec88233708ce622d926cd91a536d7e04f6c; editorial review pending	imf lang::en chapter::091 module::091-03 review::pending
IMF-091-03-0007-en	Why do luminal domains of secretory-pathway membrane proteins end up facing the cell exterior?	Signal anchors and stop-transfer sequences fix topology in the endoplasmic reticulum, and vesicle transport preserves orientation, so luminal domains become extracellular after vesicle fusion.	Integrated Medical Foundations; chapter 91, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: f4dfd75df2f98ac7d467cbbdb1662ec88233708ce622d926cd91a536d7e04f6c; editorial review pending	imf lang::en chapter::091 module::091-03 review::pending
IMF-091-03-0008-en	How can a variant cause disease even though the protein retains catalytic activity in vitro?	Function also requires correct folding, modification, assembly and targeting, so a variant that disrupts localisation leaves an active enzyme in the wrong compartment.	Integrated Medical Foundations; chapter 91, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: f4dfd75df2f98ac7d467cbbdb1662ec88233708ce622d926cd91a536d7e04f6c; editorial review pending	imf lang::en chapter::091 module::091-03 review::pending
IMF-091-03-0009-en	How does histone acetylation tend to make chromatin more accessible?	Acetyltransferases add acetyl groups that weaken the positive charge of histones and recruit readers associated with open chromatin; deacetylases reverse this.	Integrated Medical Foundations; chapter 91, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: f4dfd75df2f98ac7d467cbbdb1662ec88233708ce622d926cd91a536d7e04f6c; editorial review pending	imf lang::en chapter::091 module::091-03 review::pending
IMF-091-03-0010-en	How are DNA methylation patterns propagated through replication, and how are new patterns set?	Maintenance methyltransferase recognises hemimethylated DNA after replication and copies the pattern to the new strand, while de novo enzymes establish new patterns.	Integrated Medical Foundations; chapter 91, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: f4dfd75df2f98ac7d467cbbdb1662ec88233708ce622d926cd91a536d7e04f6c; editorial review pending	imf lang::en chapter::091 module::091-03 review::pending
IMF-091-03-0011-en	Why can defects in the same imprinted chromosomal region cause different syndromes?	Imprinted genes are expressed according to parental origin, so the syndrome depends on which parent's active allele is lost through deletion, uniparental disomy, imprinting-centre defects or methylation change.	Integrated Medical Foundations; chapter 91, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: f4dfd75df2f98ac7d467cbbdb1662ec88233708ce622d926cd91a536d7e04f6c; editorial review pending	imf lang::en chapter::091 module::091-03 review::pending
IMF-091-03-0012-en	Why can heterozygous females show variable severity of X-linked disease?	Random X inactivation in most embryonic tissues makes them mosaic, and skewed inactivation or genes escaping inactivation change how much of the affected allele is expressed.	Integrated Medical Foundations; chapter 91, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: f4dfd75df2f98ac7d467cbbdb1662ec88233708ce622d926cd91a536d7e04f6c; editorial review pending	imf lang::en chapter::091 module::091-03 review::pending
IMF-091-03-0013-en	How can a structural variant activate a gene inappropriately without disrupting any coding sequence?	Cohesin loops and boundary proteins confine enhancers to domains; removing a boundary or repositioning an enhancer lets it reach and activate the wrong promoter.	Integrated Medical Foundations; chapter 91, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: f4dfd75df2f98ac7d467cbbdb1662ec88233708ce622d926cd91a536d7e04f6c; editorial review pending	imf lang::en chapter::091 module::091-03 review::pending
IMF-091-03-0014-en	A methylation difference is found in blood between exposed and unexposed groups. Why might it not reflect modification within cells?	Exposures such as inflammation or stress alter cell composition, so the difference may reflect altered cell composition rather than changed methylation within each cell.	Integrated Medical Foundations; chapter 91, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: f4dfd75df2f98ac7d467cbbdb1662ec88233708ce622d926cd91a536d7e04f6c; editorial review pending	imf lang::en chapter::091 module::091-03 review::pending
