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Date November 2011 Marks available 1 Reference code 11N.2.HL.TZ0.1
Level Higher level Paper Paper 2 Time zone TZ0
Command term Determine Question number 1 Adapted from N/A

Question

Type I diabetes is an autoimmune disease resulting from destruction of the insulin-producing β cells in the islets of Langerhans. Islet regeneration can occur when stem cells reach the pancreas after leaving the bone marrow.

Studies have shown a link between CXCL12 and type I diabetes. Mice predisposed to develop the disease were given an inhibitor of CXCL12 for 3 weeks. The incidence of diabetes was measured after 28 weeks and compared to control mice that were not given the inhibitor.

One important chemical in the mobilization of stem cells is a protein, CXCL12, which maintains the stem cells inside the bone marrow. The breakdown of CXCL12 causes the mobilization of stem cells to the blood vessels.

The graph below shows the mobilization of stem cells and the production of mRNA for CXCL12 when the bone marrow is treated with two different chemicals (isoprenaline and clenbuterol).

Stem cells in the bone marrow can be forced into blood vessels in a process called mobilization. Mobilization of stem cells from the bone marrow into the blood vessels represents the basis for modern bone marrow transplantation procedures.

To test the effect of light on the mobilization of stem cells, mice were subjected to a simulated “jet lag” by advancing the light-dark cycle by 12 hours. This was done by subjecting mice to a 24-hour light period before the results shown in the graph were recorded. The results were compared to the stem cells in control mice under normal conditions of 12 hours of light () and 12 hours of darkness
().

Outline the effect of CXCL12 inhibition on the incidence of diabetes.

[2]
f (i).

Suggest how the breakdown of CXCL12 in the bone marrow may be related to diabetes.

[1]
f (ii).

Evaluate the possible use of isoprenaline in the treatment of diabetes.

[2]
g.

Research is being conducted into treatment for diabetes based on stem cells. Discuss the ethical issues involved in stem cell research.

[3]
h.

State the maximum number of stem cells per ml blood in the control mice.

[1]
a (i).

Determine the number of hours of light needed to release the maximum number of stem cells in blood in control mice.

[1]
a (ii).

Distinguish between the trends shown in the number of stem cells per ml blood by the mice subjected to jet lag and the control mice.

[2]
b.

Other studies suggest that a greater number of blood stem cells for transplantation may be obtained if they are harvested during darkness. Evaluate this hypothesis.

[2]
c.

Explain how the amount of mRNA for CXCL12 gives an indication of the amount of protein CXCL12 produced.

[1]
d.

Compare the effect of isoprenaline and clenbuterol with the normal release of stem cells and the production of mRNA for CXCL12.

[3]
e.

Markscheme

CXCL12 inhibition initially decreases occurrence of diabetes;
in the first 25 / up to 26/27/28 weeks;
CXCL12 inhibition does not prevent occurrence of diabetes (just delays it) / eventually the same level of diabetes

f (i).

CXCL12 breakdown allows stem cell mobilization reducing incidence of diabetes / stem cells from the bone marrow can regenerate the islets (in pancreas)

f (ii).

isoprenaline is an inhibitor of CXCL12 / inhibits synthesis of CXCL12 mRNA;
delays onset of diabetes / allows stem cell mobilization / allows islet regeneration;
does not cure the disease;

g.

suffering of patients could be reduced / diseases could be cured / better treatments developed / might replace treatment with cure;
(possibly) less cost than treating disease/diabetes;
specific example of ethical conflict; (e.g. patient groups support use of embryotic stem cells but religious groups oppose / different views on the moral status of an embryo)
restrictions on research in some countries due to cultural/religious traditions;
still in experimental stages / risk to patient;
specific example of risk; (e.g. stem cells developing into tumours / rejection / need for immunosuppressants)
death of early-stage embryos / production of embryos for stem cell research;
use of stem cells from adults/patients could overcome these objections;

h.

83 (allow whole number answers in the range of 82 to 84)

a (i).

5 (allow 4)
Do not allow answers with two different numbers.

a (ii).

more stem cells are formed in control / jet lag reduces the release of stem cells into blood stream / greater range in control;
graph is rhythmic in control / control has more regular pattern;
greater number of stem cells produced in light period in control, whereas greater number in dark period in jet lag;
graph is shifted to the right in jet lag / stem cells are released later in time in jet lag;

b.

(hypothesis supported in control) if stem cells are harvested towards the end of the dark period / (hypothesis supported) as stem cells start increasing in dark period;
(hypothesis not supported) in control as peak of stem cells occurs during light period/lowest number during dark period;
(hypothesis supported) if patient is jet-lagged as more stem cells are produced in dark period;

c.

mRNA is translated to protein / involved in protein synthesis.

d.

clenbuterol and isoprenaline both produce more stem cells than control;
clenbuterol releases fewer stem cells than isoprenaline / isoprenaline releases the most stem cells;
isoprenaline produces the least mRNA for CXCL12;
clenbuterol produces the same amount of mRNA for CXCL12 as control;

e.

Examiners report

A similar pattern of student answers was seen in f, where many were picking each individual point on the graph, rather than giving an outline as asked. Students need to pay attention to the distinction between a "describe‟ and an "outline‟.

f (i).

In f(ii) students muddled the distinction between stem cells being produced and stem cells being released.

f (ii).

N/A

g.

The ethical discussions in h were somewhat weak, with most gaining a mark for the death of early-stage embryos. Students appear to be using "fetus‟ and "embryo‟ interchangeably. Many statements were nebulous, for example referring to "playing God‟ without adequately unpacking its meaning. In bioethics, "playing God‟ refers to undertaking a controversial action unilaterally without adequate consultation with stakeholders and runs counter to the precautionary principle. In this expanded form, the notion of playing God would make for a good answer to a discuss question. Few mentioned the positive ideas of reduction of suffering.

h.

In part a most students managed to give the correct answers for maximum number (between 82-84) of stem cells per ml of blood, though some misread the graph. The maximum number needed to be a whole number.

a (i).

The number of hours (5) needed to release the maximum number of cells was correctly identified by most, though some provided a longer amount of time.

a (ii).

In b most gained either 1 or both marks. Some students described similarities when only the distinctions were required.

b.

In c, weaker answers failed to state whether or not the hypothesis was supported or not. In addition others lost marks by failing to state whether they were referring to the control or the jet-lagged mice.

c.

In d many candidates failed to make the connection between mRNA and translation, with the weakest answers describing a numerical relationship. A number misread the graph in terms of under what conditions the peaks and lowest points occurred.

d.

In e there was a tendency to give descriptive answers, stating figures from the graph, without drawing a comparison using comparative terms. As an example, "clenbuterol releases 40 stem cells‟ would not earn a mark, but "isoprenaline releases more stem cells than clenbuterol‟ is. Students must use clear comparative terms and be specific in their comparisons when there are multiple treatment groups.

e.

Syllabus sections

Core » Topic 6: Human physiology » 6.2 The blood system
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