Questions and Parts of the Specification How Science Works: Validity, reliability, peer review and how findings

are presented to the scientific community How Science Works, Point 7 Explain how scientific theories are developed, refined, supported or refuted as new data or new interpretations of data become available.

How Science Works, Point 11 Discuss the importance of critical evaluation of new data or new interpretations of data which challenge established scientific theories or propose new theories. Describe how the process of communication through journals and conferences, and peer review contribute to validation of new scientific theories by the scientific community Example Questions 1. Paragraph 7: "In general, lifespan tends to correlate with body size". Another study concluded that a larger body size caused a longer lifespan. Explain why this may not be a valid conclusion. Answers a. Correlation does not necessarily mean causation. b. In general - if size caused the lifespan to change, then the statement would always be true. c. Not enough data may have been collected to prove that the correlation is a causation. Suggest how the conclusions of the investigations conducted could be accepted by the scientific community. Answers 0. 1. 2. 3. Publish results in scientific journals Present results at conferences Peer review Any explanation for peer review (e.g. scientists in the same field conduct the experiment to check its validity whether the results are similar).

Testing on animals - risks and benefits How Science Works, Point 9 Evaluate activities in terms of their associated benefits and risks to humans, other organisms and the environment.

Example Questions 1. Paragraph 53: "With naked mole-rats, we have to start from scratch with many things". What are the advantages and disadvantages of using mole-rats (use your own knowledge, the article and the sentence above)? Answers a. It can impact the development of new treatments, theories etc. and therefore impact the rate of helping other humans. b. It is expensive and time-consuming to sequence the genome of the mole-rat. c. The mole-rats may be more useful in terms of physiology and behaviour than mice. d. Mole-rats are animals with a nervous system, so may be more unethical to test with (as with mice). e. Mole-rats live for a relatively long time, so can be studied in the long-term too. f. The behaviour of mole-rats may differ ex-situ (e.g. the Queen not being present can change behaviour); the living conditions cannot be recreated.

Unit 1: Paragraph 2 - The mole rats can help tackle strokes Paragraph 7 - They don't show signs of heart disease Paragraph 36 - Findings can give treatment for heart attacks and strokes Topic 1, Points 10-15 Describe the blood clotting process (thromboplastin release, conversion of prothrombin to thrombin and fibrinogen to fibrin) and its role in cardiovascular disease (CVD) Explain the course of events that leads to atherosclerosis (endothelial damage, inflammatory response, plaque formation, raised blood pressure). Describe the factors that increase the risk of CVD (genetic, diet, age, gender, high blood pressure, smoking and inactivity). Describe the benefits and risks of treatments for CVD (antihypertensives, plant statins, anticoagulants and platelet inhibitory drugs). Analyse and interpret data on the possible significance for health of blood cholesterol levels and levels of high-density lipoproteins (HDLs) and low-density lipoproteins (LDLs). Describe the evidence for a causal relationship between blood cholesterol levels (total cholesterol and LDL cholesterol) and CVD. Discuss how people use scientific knowledge about the effects of diet (including obesity indicators), exercise and smoking to reduce their risk of coronary heart disease. Example Questions

1. Using a named factor that can cause cardiovascular disease, explain how a stroke can arise. 2. Name and explain two current treatments for cardiovascular disease. 3. Describe two ways in which coronary heart disease can be prevented.

Paragraph 38 - Hypoxia adaptations in the lungs (gas exchange surface) Paragraph 9 - DNA and proteins - attachment of other molecules Paragraph 11 - 3D shape of proteins and importance (misfolding proteins can relate to CF [CFTR protein] too) Paragraph 15 - DNA replication (cancer mentioned throughout [e.g. paragraph 20] - a mutation can cause cancer; how does this arise?) Topic 2, Points 6-15 (Excluding some) Describe the properties of gas exchange surfaces in living organisms (large surface area to volume ratio, thickness of surface, difference in concentration) and explain how the structure of the mammalian lung is adapted for rapid gaseous exchange. Describe the basic structure of an amino acid (structures of specific amino acids are not required) and the formation of polypeptides and proteins (as amino acid monomers linked by peptide bonds in condensation reactions) and explain the significance of a proteins primary structure in determining its three-dimensional structure and properties (globular and fibrous proteins and types of bonds involved in three-dimensional structure). Explain the mechanism of action and specificity of enzymes in terms of their three-dimensional structure and explain that enzymes are biological catalysts that reduce activation energy, catalysing a wide range of intracellular and extracellular reactions. Describe the basic structure of mononucleotides (as a deoxyribose or ribose linked to a phosphate and a base, ie thymine, uracil, cytosine, adenine or guanine) and the structures of DNA and RNA (as polynucleotides composed of mononucleotides linked through condensation reactions) and describe how complementary base pairing and the hydrogen bonding between two complementary strands are involved in the formation of the DNA double helix. Describe DNA replication (including the role of DNA polymerase), and explain how Meselson and Stahls classicexperiment provided new data that supported the accepted theory of replication of DNA and refuted competing theories Describe a gene as being a sequence of bases on a DNA molecule coding for a sequence of amino acids in a polypeptide chain. Outline the process of protein synthesis, including the role of transcription, translation, messenger RNA, transfer RNA and the template (antisense) DNA strand Explain how errors in DNA replication can give rise to mutations and explain how cystic fibrosis results from one of a number of possible gene mutations.

Example Questions 1. Why is the 3D structure of proteins critical to functioning? Paragraph 1 Ethics of animal testing: utilitarian approach to animal testing- working for greater good. Paragraph 3 Adaptations of nekked mole rat to environment: Large teeth to burrow with underground No fur as they live in hot conditions therefore not required Due to dark underground conditions they are dependent on their heightened sense of smell, whiskers used as pressure points Paragraph 4 Part of eusocial society where queen bee is only actively reproducing female and only a hand full of actively reproducing males. Everyone else is infertile. This constant in breeding results in reduction of genetic variation (which reduces chances of speciation) Possible question may be 'how is genetic variation obtained?' -independent assortment -crossing over -random fertilisation What are disadvantages of having no genetic variation? Paragraph 5 Comparing homeotherms (like humans-we regulate our body temperature) to poikilotherms-those whose body temperature is dependent on environmental temperature. There may be a question with regards to homeostasis in humans and regulating body temp? Paragraph 6 ...notice how they constantly put name of specialist, area they specialise in and the institution they work at-highlights credibility of sources Further questions: 1. What two features of the NMR drew scientists attention? 2. Explain how the altered cells carrying the cancer causing genes were made and the possible ways of transferring it to the immune-compromised mice? 3. Explain the two-tiered contact inhibition. 4. Define reflex action 5. it turns out that high levels of carbon dioxide affect the types of nerves that the NMR have disconnected explain this statement using your knowledge of the nervous system. 6. What are the two evolutionary adaptations of NMR? 7. Outline the process of genetic finger printing. 8. What are the disadvantages of in-breeding?

NOTES ON THE CASE STUDY UNIT 5 1. Thermoregulation and its importance Thermoregulation is the ability of an organism to maintain its body temperature within narrow limits even when the external temp changes. It is an aspect of homeostasis (maintenance of a constant internal environment) and enables an optimum temp to be maintained for maximum enzyme activity. 2. The naked mole rat is classified as poikilothermic rather than homeothermic explain All mammals except for the mole rat are homeotherms meaning they can maintain a relatively constant body temperature. The naked mole rat is a thermoconformer, meaning its body temperature changes with the surrounding temperature. There is evidence in its morphology to suggest that its not a homeotherm. For e.g. unlike other mammals, it lacks fur and has a marked reduction in sweat glands. Less sweat evaporated means water is conserved and latent heat of vaporization is conserved. Instead of fur, it has a thicker epidermal layer which probably offers protection and acts as a thermal insulator. Its skin is loosely folded. The folds probably trap warm air which is a poor conductor of heat and helps it to live in the cold tunnels. The pigment containing cells are found in the dermis of the skin unlike in the epidermis like in typical mammals. This probably facilitates the retention of heat within the mammal. They probably also use some behavioral aspects of thermoregulation such as huddling together when cold to reduce surface area for heat loss and exchange of body heat or bask in the sun when its cold. If they are too hot, they may move deeper into the burrow. It has a very low metabolic rate (low rate of respiration) since it doesnt need to maintain a constant body temperature. Therefore, it uses less oxygen (recall the role of oxygen). 3. Is the behavior in an eusocial society innate or learned? Innate 4. What adaptations are shown in the picture? Their large, protruding teeth are used to dig, and their lips are sealed just behind the teeth to prevent soil from filling their mouths while digging (anatomical adaptations to their niche). 5. Para 7 lifespan tends to correlate with body size Explain what is meant by a correlation Its a relationship between 2 variables. When 1 variable changes there is a change in the accompanying variable. According to this para, as the body mass of the animal increases, their life span in years also increases. A Spearman Rank correlation test has to be done to establish a positive correlation. The naked mole rat seems to be an exception to this as they live for 3 decades!

6. Discuss the ethics of using naked mole rats for research. Absolutists say that animals should not be used under any circumstance as the experiment causes them discomfort/pain. Relativists say that animals can be used under certain circumstances provided that the overall expected benefits of the research are greater than the overall expected harms. In this case, one can justify using mole rats to study how to tackle cancer (as they never get cancer) and also to study the process of ageing and how to slow it down/reduce effects of ageing, since naked mole rats have astonishing longevity. That is, their bones remain strong and they dont show signs of heart disease or mental decline. They age very little until the very end of their lives. It would be useful to study the biochemistry behind these phenomena to try to reduce the effect of ageing in humans.

7. Structure of Proteins Each type of protein has a unique primary structure number and sequence of amino acids in the polypeptide chain. This determines the position of R groups. The polypeptide chain folds in such a way so that ionic, hydrogen and disulphide bonds can form between R groups. These bonds form in fixed places in a given type of protein and maintain the tertiary structure. 8. How do people age? Organisms age because cells accumulate free radical damage over time. Oxygen containing free radicals attach to proteins and DNA and damage them. In the case of proteins, oxidative damage causes bonds in the tertiary structure to break. Therefore, the polypeptide chain partly unravels and the 3D globular structure is lost. Thus, in the case of enzymes, the substrate of complementary shape can no longer bind and hormones can no longer bind to their receptors. In mice, interventions that enhance oxidative damage reduce lifespan. 9. What causes cancer? Cancer is caused by a mutation in either the proto-oncogenes (making them oncogenens) or in the tumor suppressor genes. These genes code for proteins that control the cell cycle. Without these proteins, there is uncontrolled mitosis and the rate of cell formation is greater than the rate of cell death leading to cancer. The phenotype of cancer is influenced by both the genotype and the environment. Environmental triggers damage DNA increasing the risk of mutations. Mutations causing cancer accumulate with age because every time a cell divides, DNA replicates and errors can occur during DNA replication. 10. What is meant by immune-compromised mice? (para 13). They have a reduced number of T helper, T killer and B cells (probably due to a lack of cytokines) and also reduced number of phagocytes. With reference to this para, that means that the cancerous cells cannot be kept in check and they multiply to cause tumors. 11. What does telomerase do? Its an enzyme which increases the length of pieces of DNA which are shortened when a cell divides by mitosis (advantage). Increased telomerase activity increases the rate of cancer (disadvantage). 12. Why do small rodents have high levels of telomerase? Rats are more likely to die of hunting rather than old age. So nature has allowed rats a slim cancer risk in exchange for active telomerase activity to speed healing (Since telomerase helps cell division). Refresh your memory on gene expression signal proteins (usually hormones) bind to receptors on the plasma membrane of the target cell. This activates a second messenger which in turn moves to the nucleus and activates transcription factors (proteins). These together with RNA polymerase bind to the promoter initiating transcription. mRNA is then translated to give a polypeptide chain with a specific sequence of amino acids. 13. What aspects of the Naked mole rats explain their longevity? (i) The naked mole rats have proteins that can withstand significantly more oxidative damage before they lose their shape when compared to mouse proteins.

(ii)

Naked mole rats have a remarkable ability to avoid cancer. Analysis by Buffenstein and Hornsby showed that these cells were inhibited from replicating. They deduced that naked mole rats have mechanisms in place to detect any abnormalities in DNA and to control those cells having the abnormalities so that they dont divide and pass them onto other cells. But these mechanisms are not explained in the passage. The passage seems to focus on (iii). Gorbunova found out that there is a kind of overcrowding early-warning gene that the naked mole rat expresses in its cells. This gene called p16 makes the cells "claustrophobic," stopping the cells from dividing when too many of them crowd together. This cuts off uncontrolled mitosis before it can start. Human cells also cease replication when their population becomes too dense but, this mechanism called contact inhibition, occurs at a lower limit of cells in the naked mole rat compared to other mammals/humans (thats why in the experiment, the cells refused to divide further when a certain number of them occupied a space in a Petri dish). All organisms including mole rats and humans have the P27 gene which prevents cellular overcrowding but at a much later point than P16 does . Since the mole rats possess P16 as well as P27, they seem to have a double barrier or two tier contact inhibition that a cell must overcome before it can divide uncontrollably. This explains their resistance to cancer.

(iii)