Frailty and Ageing

Question 1

Sarcopenia describes the loss of muscle mass and strength that occurs in conjunction with biological ageing. Which of the following hormonal and alterations is thought to contribute to the development of the sarcopenia?

Increased growth hormone secretion

Increased IGF-1 concentration

Increased myostatin concentration

Increased oestrogen secretion

Increased testosterone production

Answer 1

Increased myostatin concentration

Question 2

Biological ageing in humans is proposed to occur as a result of free radical exposure. By what mechanism is this proposed to contribute to ageing?

Alteration of a RNA splicing

Lowering of the Hayflick limit

Oxidation of macromolecules

Shortening of chromosomes

Upregulation of gene transcription

Answer 2

Oxidation of macromolecules

Question 3

Progerias such as Werner’s syndrome and Hutchinson Gilford syndrome are a set of rare diseases characterised by premature ageing. In these conditions cells enter into early senescense , a state in which cell division is arrested.

Which enzyme involved in the DNA replication is hypothesised to play a role in these conditions?

Gyrase

Ligase

Helicase

Telomerase

Topoisomerase

Answer 3

Helicase

Question 4

The fast and efficient folding of newly synthesised proteins is catalysed by which class of enzyme in protein misfolding disorders such as Parkinsons, Alzheimer’s and prion diseases?

Chaperonins

Cyclophilins

Peptidyl dipeptidases

Peptidyl prolyl cis-trans isomerases

Proetin disulphide isomerases

Answer 4

Chaperonins

Question 5

Many genetic mutations have been identified that cause cystic fibrosis. Class II mutations affect the post translational folding of the protein leading to loss of function due to errors in tertiary structure. Where in this cell does this folding occur?

Nucleus

Endoplasmic reticulum

Mitochondrion

Cytoplams

Plasma membrane

Answer 5

Endoplasmic reticulum

Question 6

Ubiquitination is a protein post-translational modification process that attaches ubiquitin to a protein. This process please and important role in the HIF pathway by marking HIF-1 alpha for degradation. What is ubiquitin?

Amino acid

Metal ion

Protein

Sugar moiety

Inorganic chemical

Answer 6

Protein

Question 7

You are revising muscle contraction which occurs in both skeletal muscle and non-pacemaker regions of the heart depend upon electrical excitation of myocytes/myofibres by an action potential. You note that the shape of the action potentials in these two tissues difference in their shape and duration. These differences can be explained by which ionic current?

inward long-lasting calcium current

inward transient calcium current

inward fast sodium current

inward slow sodium current

outward potassium current

Answer 7

inward long-lasting calcium current

Question 8

Skeletal muscle contraction requires opening of ion channels known as dihydropyridine receptors on the sarcolemma. What type of ion channels are these?

ligand-gated calcium channels

liand-gated potassium channels

voltage-gated calcium channels

voltage-gated potassium channels

voltage gated sodium channels

Answer 8

voltage-gated calcium channels

Question 9

Cardiomyocyte contraction is initiated by a rise in intracellular calcium mediated by the release of the ion from the sarcoplasmic reticulum. To which protein does Ca++ then bind?

Actin

Myosin

Tropomyosin

Tropnonin C

Troponin I

Answer 9

Tropnonin C

Question 10

You are a researcher investigating the role of platelet-derived growth factor (PDGF) signalling in airway remodelling in asthma. PDGF signals for cell proliferation via binding to its receptor leading to the activation of Janus kinase (JAK). Active JAK then phosphorylates Signal transducer and Activator of Transcription proteins enabling them to dimerise and translocate to the nucleus. Which protein domain of STAT is required for this dimerisation?

GTPase domain

Phosphatase domain

Serine?threonine kinase domain

SH2 domain

Tyrosine kinase domain

Question 11

Ras is a signalling molecule activated following binding of growth factors such as epidermal growth factor (EGF) to its receptor. Activity of the signalling pathway is dependent upon the net balance of a number of signalling and regulatory components. What change to the signalling pathway would promote cell proliferation?

decreased rasGAP activity

decreased rasGEF activity

decreased ras activity

increased GDP/GDP ratio

increased protein tyrosine phosphatase activity

Answer 11

decreased rasGAP activity

Question 12

The TG N1412 clinical trial made headlines in 2006 as a result of severe side-effects in six individuals given a potential new superagonist drug during a Phase 1 trial. What was the primary purpose of this trial?

to compare the new drug with the gold standard therapy

to determine the effectiveness of the new drug

to determine the safety of the new drug

to establish the optimal dose of the new drug

to establish the optimal mode of administration of the new drug

Answer 12

to determine the safety of the new drug

Phase 1 assess the safety of drug or technology in a small number of healthy volunteers.

Question 14

Cell death can be assessed in a number of ways in the laboratory including visualisation of chromatin condensation, membrane blebbing or uptake of dye (eg Tryptan blue) by microscopy. Other methods involve assessment of the DNA laddering gel electrophoresis and activation of caspase enzymes by fluorescence-based methods.

A positive result in which method would suggest necrosis rather than apoptosis?

Caspase activation

Chromatin condensation

DNA laddering

Membrane laddering

Uptake of dye

Answer 14

Uptake of dye