hllj/quesmed huggingface dataset:
Initiated by CyclinE/CDK2, which of the following describes replication licensing?

Options:
explanation: Primer addition is a vital process in DNA replication in both bacteria and eukaryotes and is mediated by DnaG in bacteria and primase in eukaryotes. In eukaryotes, there is an extra step in which a DNA primer is added by DNA Pol-alpha. Further differences exist such as the removal of primers in bacteria by DNA Pol-1 via nick translation, compared to the removal of RNase H1 and flap endonuclease-1 then replacement by DNA pol-delta in eukaryotes.
name: Primase adds RNA primers to DNA strands, providing a basis for DNA polymerase activity on the leading strand and Okazaki fragments
label: d
answer: no
explanation: The 5' m7G cap of mRNA is required by most mRNAs for binding to the small ribosomal subunit. This can however be overcome by internal ribosome entry sites on some eukaryotic and viral mRNAs resulting in cap-independent translation.

<br>
name: The 5' m7G cap of mRNA mediates binding to the 40S subunit of the eukaryotic ribosome
label: e
answer: no
explanation: This is the spindle assembly checkpoint (SAC). When the SAC is satisfied, CDC20 is released and bound to APC/C, allowing it to ubiquitinate securin (and cyclin B) for degradation. Securin inhibits separase, so the ubiquitination of securin dis-inhibits separase which then cleaves the Scc1 component of cohesin. This allows chromatid separation by the contractile forces of kinetochore-microtubule depolymerisation, initiating anaphase.
name: Once each kinetochore is attached to two microtubules from opposite poles, anaphase can begin
label: c
answer: no
explanation: This is replication licensing, the process by which a finite number of the available origins are selected to be utilised before DNA replication begins to avoid under-replication or re-replication of the DNA.
name: Loading of MCM2-7 helicases onto origins of DNA replication
label: a
answer: yes
explanation: This occurs during the signalling that initiates replication, but is not replication licensing. Once Myc is activated, it promotes the transcription of Cyclin D which binds to CDK4 which in turn phosphorylates the retinoblastoma protein so that it can dissociate itself from E2F1. E2F1 then promotes Cyclin E transcription, moving the cell cycle from the G0 to G1 stage.
name: Mitogens act through tyrosine kinase receptors, activating Ras-Raf-Mek-MAPK signalling which activates pro-mitogenic transcription factors such as Myc
label: b
answer: no

Correct answer: a
Upon DNA damage, which of these processes occur as part of a mechanism to prevent cell cycling until the damage is repaired?

Options:
explanation: This occurs during the initiation of the cell cycle and is stimulated by mitogen pathways. It results in E2F1 promoting the transcription of Cyclin E. Excess CDK4-Cyclin D activity due to gain of function or over-expression is a common mechanism utilised by breast cancer cells and glioblastomas.
name: CDK4-Cyclin D phosphorylates retinoblastoma protein, dissociating it from E2F1
label: d
answer: no
explanation: This process occurs normally during the cell cycle, acting as a molecular switch. APC-CDH1 ubiquitinates Cyclin A to cause its degradation. CDK2-Cyclin A binds and phosphorylates CDH1, inactivating APC-CDH1. In G1, Cyclin A synthesis is low so APC-CDH1 predominates however, once the synthesis of Cyclin A is sufficient, the balance is shifted and CDK2-Cyclin A inhibition of APC-CDH1 predominates. The resultant rise in CDK2-Cyclin A promotes the shift from G1 to the S-phase.
name: CDK2-Cyclin A is activated, activating a negative feedback loop on APC-CDH1
label: c
answer: no
explanation: Once these kinases are activated, one of their actions is to phosphorylate Chk1/2 kinases which phosphorylate Wee1 kinase and Cdc25 phosphatase, activating and inhibiting them respectively. This results in increased phosphorylation of CDK1, inhibiting CDK1-Cyclin B complexes and inhibiting cell cycle progression at the G2/M checkpoint. This is known as the DNA damage checkpoint.
name: ATM/ATR kinases detect the free ends of damaged DNA
label: a
answer: yes
explanation: APC-CDC20 does ubiquitinate Cyclin B to promote its proteasomal degradation, but this is a normal process in mitosis, occurring at the start of anaphase alongside the degradation of securin and allowing the chromatids to separate.

<br>
name: APC-CDC20 promotes the degradation of Cyclin B, inhibiting G2/M progression
label: e
answer: no
explanation: These SMADs activate p107 binding to E2F4 which represses transcription of Cyclin E. SMADs also activate p15-INK4b which in turn represses CDK4-Cyclin D to further decrease Cyclin E transcription. This describes the inhibition of replication by external signals which prevents the G1/S transition, rather than the DNA damage checkpoint.
name: Anti-mitogens such as TGF-B bind receptors, activating SMADs
label: b
answer: no

Correct answer: a
The formation of the mitochondrial outer membrane pore (MOMP) leads to which of the following events?

Options:
explanation: Cytochrome C molecules released by the MOMP activate APAF1 which associates with pro-caspase 9 to form the apoptosome. Pro-caspase 9 is then cleaved, activating its own protease activity. Caspase 9 cleaves effector caspases 3 and 7 which activate apoptotic enzymes such as caspase-dependent DNase.
name: Pro-caspase 9 is cleaved
label: a
answer: yes
explanation: Cytochrome C molecules released by the MOMP activate APAF1 which associates with pro-caspase 9 to form the apoptosome. Pro-caspase 9 is then cleaved, activating its protease activity. Caspase 9 cleaves effector caspases 3 and 7 which activate apoptotic enzymes such as caspase-dependent DNase.
name: Released cytochrome C inhibits APAF1
label: d
answer: no
explanation: BH3-only is a protein activated by p53 after DNA damage or endoplasmic reticulum stress. It activates BAX/BAK which oligomerises in the mitochondrial outer membrane to form a pore through which factors including cytochrome C can be released to cause apoptosis. This action is therefore upstream of the MOMP.

<br>
name: BH3-only activates BAX/BAK
label: e
answer: no
explanation: XIAP is an inhibitor of apoptosis that is constitutively active in cells and inhibits the activity of caspase 9 in the apoptosome and effector caspases 3 and 7 to prevent the inappropriate activation of apoptosis. XIAP levels decrease upon apoptotic signalling. In type 1 cells (mostly immune cells), this is initiated by the activation of death receptors without the need for a MOMP. In type 2 cells (most other cells), this is mediated by MOMP release of SMAC which inhibits XIAP.
name: XIAP levels rise
label: c
answer: no
explanation: Caspase 8 is an initiator caspase which is activated by proximity to other caspase 8 molecules. This occurs upon trimeric death receptor activation by extracellular ligands, resulting in the recruitment of FADD to the cytoplasmic components which in turn recruits caspase 8. Caspase 8 can then cleave effector caspases 3/7 or cleave BID to tBID to activate BAX/BAK formation of the MOMP. This action is therefore upstream of the MOMP.
name: Caspase 8 activation
label: b
answer: no

Correct answer: a
Topoisomerase inhibitors prevent which part of DNA replication?

Options:
explanation: Due to the twisting nature of DNA, the progression of the replication fork rapidly causes super-coiling of the DNA which halts further progression unless topoisomerases cut the DNA and unwind it. Topoisomerase 1 cuts a single strand to unwind single DNA double helices, whilst topoisomerase 2 cuts both strands of the double helix to allow another to pass through to unwind the super-coiling. Topoisomerase inhibitors, therefore, inhibit replication fork progression and are used as antibiotics and chemotherapeutics.
name: Replication fork progression
label: a
answer: yes
explanation: DNA polymerase 3 is the leading strand DNA polymerase in bacterial DNA replication. Its continuous activity without dissociation during the replication of the leading strand is facilitated by its association with the sliding B-clamp processivity factor. Topoisomerases are not directly involved in this process.
name: DNA polymerisation
label: d
answer: no
explanation: DnaG is the bacterial primase which adds a single RNA primer to the leading strand and numerous RNA primers to the lagging strand to prime each Okazaki fragment. Topoisomerases are not directly involved in this process.
name: Priming by an RNA primer
label: c
answer: no
explanation: In bacteria, primers are replaced by DNA polymerase 1 which mediates nick translation. This involves the removal of RNA nucleotides and replacement with DNA nucleotides in the 5' to 3' direction. Once DNA polymerase 1 dissociates, the strands are re-joined by DNA ligases. Topoisomerases are not directly involved in this process.

<br>
name: Primer replacement
label: e
answer: no
explanation: DnaA is the origin recognition complex used to bind DnaA boxes, unwind AT-rich regions and load DnaC. This loads the DnaB helicase and then the DnaG primase, the DNA polymerase 3 holoenzyme and the B-clamp processivity factors to form the bacterial DNA replication complex. Topoisomerases are not directly involved in this process.
name: Binding of DnaA to bacterial origins
label: b
answer: no

Correct answer: a
Rho-dependent could be used to describe which of the following processes?

Options:
explanation: The spliceosome mediates RNA splicing at GT-AG consensus sequences. A 2' -OH group from the 3' end of an intron undergoes hydrophilic attack of a phosphate group at the 5' end of the intron, and is followed by the newly free 3' -OH group of the 5' exon attacking the phosphate of the 3' exon. This results in the removal of the intron in a circular lariat. Rho is not involved.

<br>
name: pre-mRNA splicing
label: e
answer: no
explanation: The stop codons UAA, UAG and UGA are complementary to release factor, a protein which binds to the A-site of the ribosome and causes the dissociation of the small and large ribosomal subunits. Rho is not involved.
name: Termination of translation
label: c
answer: no
explanation: Transcription is initiated when a promoter site is bound by the components of the pre-initiation complex. In eukaryotes, there is a TATA consensus motif 25 bases upstream of the translation start site to which TF2D (with the TATA-binding protein), other general transcription factors and RNA polymerase 2 bind to form the pre-initiation complex. Rho is not involved.
name: Initiation of transcription
label: b
answer: no
explanation: Rho-dependent termination occurs when the rho RNA helicase binds newly-translated C-rich RNA followed by a GC-rich hairpin and unwinds the RNA-DNA complex to mediate dissociation. In contrast, rho-independent termination of transcription occurs when the RNA polymerase reaches a palindromic GC-rich DNA sequence followed by an AT-rich DNA sequence and pauses then dissociates, with the RNA adopting a GC-rich hairpin and a string of uracils.
name: Termination of transcription
label: a
answer: yes
explanation: Translation is initiated when the small ribosomal subunit binds the 5' m7G cap (or IRES sequence) of an mRNA molecule. It then scans along the mRNA until the AUG start codon, at which point the large ribosomal subunit associates and the methionine tRNA is recruited to the A-site and translation begins. Rho is not involved.
name: Initiation of translation
label: d
answer: no

Correct answer: a
Picornaviruses use which method in their mRNAs to get hosts to express their proteins?

Options:
explanation: Picornavirus RNAs have IRES sequences in their RNAs which form 3-dimensional structures and bypass the need for 5' 7mG caps.
name: Internal ribosome entry sites (IRES)
label: a
answer: yes
explanation: Stealing 5' 7mG caps from host mRNAs is a viral DNA changing method employed by influenza's RNA-dependent RNA polymerases, but not by picornaviruses.
name: 5' cap stealing
label: b
answer: no
explanation: Intron removal by pre-mRNA splicing is not done in viruses as they contain no introns in their genomic material.

<br>
name: Intron removal by pre-mRNA splicing
label: e
answer: no
explanation: Cleaving 5' 7mG caps from host mRNAs is a change mediated by picornaviruses, but is not a change to picornavirus mRNAs.
name: 5' cap cleavage
label: c
answer: no
explanation: Highly active promoters are used by most viruses, including the 5' promoter element of picornavirus RNA genomes, but this is a constitutional state of viral genomic RNA rather than a change to mRNAs.
name: Use of highly active promoters
label: d
answer: no

Correct answer: a
A single nucleotide change causing a stop codon and truncating a protein without changing any subsequent amino acids is called what?

Options:
explanation: A missense mutation is a single nucleotide substitution which produces a non-redundant codon change, but does not introduce a stop codon. An example is the BRAF V600E mutation in cancers such as melanoma.
name: Missense
label: b
answer: no
explanation: This would not be a single nucleotide change as to remain in-frame, deletions must occur in multiples of 3 nucleotides. In-frame additions and deletions are common at 3-nucleotide repeat microsatellites, such as the CAG repeats in the Huntingtin gene.
name: In-frame deletion
label: c
answer: no
explanation: A frameshift mutation occurs upon the addition or deletion of nucleotides (not in multiples of 3) which alter the reading frame of the mRNA, meaning each subsequent amino acid is different. This makes the protein misfold and become non-functional.
name: Frameshift deletion
label: d
answer: no
explanation: A nonsense mutation is a single nucleotide substitution which produces a stop codon (UAA, UAG or UGA), truncating the protein without changing any other amino acids.
name: Nonsense
label: a
answer: yes
explanation: Splice-site mutations occur when a GT-AG splice consensus site is added or removed by a missense mutation. These can cause the inclusion of an intronic sequence or the removal of an exon. An example of a splice-site mutation is the  MYBPC3 gene in hypertrophic cardiomyopathy.

<br>
name: Splice-site mutation
label: e
answer: no

Correct answer: a
Xist, H3K27me3 and H3K9me3 are all associated with which process?

Options:
explanation: Transcription is up-regulated by enhancer elements which recruit enzymes such as p300, a histone acetylase which de-represses the target gene promoters that the sequences are folded to be adjacent to. Up-regulation of transcription does not involve Xist.
name: Up-regulation of transcription
label: d
answer: no
explanation: In cells with multiple X-chromosomes, one chromosome expresses Xist, a long non-coding RNA which coats the X-chromosome from which it is expressed and recruits a polycomb repressive complex which uses EZH2 to catalyse H3K27me3 formation. This results in the recruitment of SETDB1 which catalyses the formation of H3K9me3. DNA methyltransferases then methylate the DNA, and laminin B receptors are recruited to anchor the newly condensed Barr body to the nuclear membrane.
name: X-inactivation
label: a
answer: yes
explanation: Genomic imprinting is the process by which a subset of genes is expressed in a parent-of-origin-specific manner. This is mediated by the differential methylation of imprinting control regions during epigenetic reprogramming in utero. Genomic imprinting does not involve Xist.
name: Genomic imprinting
label: b
answer: no
explanation: Up-regulation of translation can be mediated by epi-transcriptomic changes. m6Adenine marks are the most common, added by METTL3/METTL14 at RRACH motifs. m6A binding proteins contain domains such as YTHDF2 which enhances mRNA translation. Up-regulation of translation does not involve Xist.

<br>
name: Up-regulation of translation
label: e
answer: no
explanation: Endogenous retroviruses are suppressed by specific KRAB zinc finger proteins binding to endogenous retroviral sequences and recruiting KAP1 to induce repressive chromatin remodelling using NuRD, HDAC and SETDB1. This promotes the methylation of endogenous retroviral promoters to repress transcription. piwi RNAs are also used during epigenetic reprogramming in germ cells and the blastocyst to prevent transcription when epigenetic markers are removed. Endogenous retrovirus suppression does not involve Xist.
name: Endogenous retrovirus suppression
label: c
answer: no

Correct answer: a
A neutral, non-visible genetic variant in a small, isolated island population founded by a single boat is unlikely to be in Hardy-Weinberg equilibrium because of what failed criterium?

Options:
explanation: A small island population founded by a single boat is unlikely to have a large enough population for the Hardy-Weinberg equilibrium to be applicable. Small populations increase the effect of random chance during mating on the proportion of a population with a specific genotype, increasing the chance of a genetic variant becoming fixed in a population, such as pp = 1.
name: Population size
label: a
answer: yes
explanation: A neutral variant is by definition not selected for or against. If a variant were to be selected for or against, the proportion surviving and reproducing would become non-random and disrupt the Hardy-Weinberg equilibrium by altering the proportions of each genotype. For example, if the q variant was selected against, the population proportions would shift towards pp = 1.
name: Selection
label: c
answer: no
explanation: A neutral, non-visible genetic variant is unlikely to affect mating choices. If it were to affect mating choices, then mating would become non-random and disrupt the Hardy-Weinberg equilibrium by altering the proportions of each genotype. For example, if individuals with pp genotypes attracted pp genotypes and qq genotypes attracted qq genotypes, the proportions would shift towards pp + qq = 1.
name: The variant affects mating choices
label: d
answer: no
explanation: An isolated population is unlikely to have significant migration. If there was migration, individuals with different genotypes may not immigrate or emigrate in equal proportions to their respective population size, altering the proportions of each genotype on the island.
name: Migration
label: b
answer: no
explanation: Although this is possible, it is very unlikely. Indeed, the population size is much more likely to affect the suitability for Hardy-Weinberg equilibrium. New mutations would disrupt the formula pp + 2pq + q = 1 by introducing another genetic variant, 'r'.

<br>
name: New mutations arise in the gene locus
label: e
answer: no

Correct answer: a
Which of the following describes shunting inhibition?

Options:
explanation: This describes spatial inhibition. This is a method by which an inhibitory synapse can make action potential firing less likely without negating signals from separate dendrites.
name: Inhibitory synapses on different dendrites to excitatory synapses subtract from their excitatory potential
label: d
answer: no
explanation: This describes shunting inhibition. This is a powerful way for excitatory potentials to be diminished, effectively turning the dendrite into a NOT logic gate in which sufficient excitatory synapses must be active, but not the inhibitory synapse, for an action potential to be stimulated.
name: Inhibitory synapses which are closer to the soma than excitatory synapses on the same dendrite divide the excitatory potential
label: a
answer: yes
explanation: This describes pre-synaptic inhibition. This is a powerful method by which an inhibitory synapse can entirely stop the chance of an action potential firing (but requires accurate timing).

<br>
name: Inhibitory synapses towards the end of an axon hyperpolarise the synaptic terminal as the action potential reaches it, preventing neurotransmitter release
label: e
answer: no
explanation: This describes temporal summation. This is the method by which strong signals through a smaller number of weak excitatory synapses can sum together to stimulate action potentials.
name: Multiple excitatory potentials transmitted rapidly after one another sum at the soma
label: c
answer: no
explanation: This describes spatial summation. This is the method by which multiple weak excitatory synapses from different sources can sum together to stimulate action potentials.
name: Multiple excitatory synapses on different dendrites sum their excitatory potentials at the soma
label: b
answer: no

Correct answer: a
Which of the following statements about skeletal muscle excitation-contraction coupling is true?

Options:
explanation: Action potentials propagate down transverse tubules to a triad structure consisting of a transverse tubule and two cisternal ends of sarcoplasmic reticulum. At these triads, modified dihydropyridine receptors which themselves cannot cause calcium flux alter their conformation when the membrane is depolarised, causing allosteric interaction with attached ryanodine receptors on the sarcoplasmic reticulum. This allows calcium to move down its electrochemical gradient from the sarcoplasmic reticulum into the sarcoplasm.
name: Action potentials activate dihydropyridine receptors coupled with sarcoplasmic reticulum ryanodine receptors, causing calcium release into the sarcoplasm
label: a
answer: yes
explanation: Muscle cells use ACh which binds nAChRs to achieve this initial depolarisation which stimulates neighbouring sodium channels to open, generating an action potential which spreads across the muscle cell.
name: Glutamate binds NMDA and AMPA receptors on skeletal muscle membranes, opening channels which allow sodium entry and depolarising the muscle cell
label: b
answer: no
explanation: Calcium flux through dihydropyridine receptors occurs in cardiac muscle but not skeletal muscle. This is necessary due to the poorly developed transverse tubules, particularly in the atria which only have caveolae.

<br>
name: Action potentials activate dihydropyridine receptors which subsequently allow calcium flux into the cytoplasm. This induces calcium-induced calcium release via ryanodine receptors on the sarcoplasmic reticulum
label: e
answer: no
explanation: Caldesmon is used in smooth muscle for this role whilst skeletal and cardiac muscle use troponin. In smooth muscle, there is also modulation of caldesmon activity by phosphorylation by protein kinase C (downstream of PLC which generates DAG and IP3 from PIP3) and modulation by calcium-calmodulin complexes.
name: Upon calcium flux into the cytoplasm, caldesmon undergoes a conformational change, removing tropomyosin from actin-binding sites, and allowing myosin cross-bridging
label: c
answer: no
explanation: Latch bridges are only formed in smooth muscle. These are used to fix the muscle at a set length without continuous ATP consumption. This occurs when myosin is dephosphorylated when it is bound to actin, whereas dephosphorylation when myosin is not bound to actin causes relaxation. Myosin is constantly activated in skeletal muscle, and the limiting factor is troponin moving tropomyosin to reveal actin binding sites, rather than myosin phosphorylation.
name: After contraction initiation, if myosin phosphatase removes the phosphate group from myosin, latch bridges are formed
label: d
answer: no

Correct answer: a