Page 1 of 16

Scientific Article Notes, Question and answers, June 2013 Unit 5, by Stafford Valentine Redden (M.Sc.; M.Ed.; M.A.; Ph.D)
Scientific article for use with Question 7 Naked and ugly: The new face of lab rats 1. In a small room in the lab-animal wing of the University of Illinois at Chicago, biologist Thomas Park peers into a plastic box full of naked mole rats. You guys are so cute, he says softly, in a voice usually reserved for babies or puppies. 2. Park is mistaken. Naked mole rats are not cute. They are bald, wrinkled and purply pink, with tiny near-blind eyes and huge yellow teeth. Ranging from the size of a large mouse to that of a small rat, these odd rodents are among the strangest looking mammals on the planet. But dont judge a naked mole rat by its unfortunate appearance. These bizarre creatures could help us tackle all sorts of human maladies, from cancer and stroke to pain relief and ageing. Paragraph 2 SAQ1. Explain the formation of tumors (cancers). Cancer is caused by gene mutations (in tumor suppressor genes or oncogenes: which are responsible for regulation of the cell cycle) which cause uncontrolled cell division. The rate of cell proliferation is greater than the rate of cell death. SAQ2. Explain how stroke may be caused. Atheroma formation and thrombosis in cerebral arteries (or other arteries in the brain) lead to ischaemia (lack of blood flow and oxygen supply) in the brain. This leads to necrosis (death) of neurons in the brain. This is the main cause of stroke. High blood pressure can also cause rupture of arteries in the brain, leading to necrosis of brain cells. SAQ3. State the risk factors for stroke. High blood pressure, high LDL levels, lack of exercise, ageing, gender, smoking, genetic factors and diet. SAQ4. Explain the causal link between ageing and stroke. Ageing makes the arteries less elastic. This increases blood pressure and causes endothelial damage. T cells and monocytes migrate into the smooth muscle layer of arteries and facilitate the deposition of Ca2+ ions, LDL cholesterol and cells debris to form atheroma or plaque. This narrows the lumen of arteries in the brain and increases the risk of stroke. SAQ5. Pain is caused when specific receptors called A (delta) receptors and C fiber receptors are stimulated. Using your knowledge about ion movement in a neurone, explain how an action potential will be initiated in these neurons. The stimulus will cause the Na+ ion channels to open. The influx of Na+ ions into the neuron will initiate the formation of an action potential. SAQ6. Suggest mechanisms by which the mole rat may provide relief from pain. They may produce some chemicals (analgesics) which may block pain receptors at the synapses and prevent post synaptic potentials from forming in the neurons that are responsible for the sensation of pain.

Comment [S1]: To look intently or searchingly

Comment [S2]: Mice measure between 3 and 14 inches in length and weigh up to 2 ounces. Rats may be as long as two feet and weigh more than mice. The snout of the rat is more pointed. Comment [S3]: mammals, characterised by a single pair of continuously growing incisors in each jaw which must be kept short by gnawing. Comment [S4]: Strikingly unconventional and far-fetched in style or appearance Comment [S5]: To make a determined effort to deal with a difficult problem or situation. Comment [S6]: Any undesirable or disordered condition Comment [S7]: Known medically as a malignant neoplasm, is a broad group of various diseases, all involving unregulated cell growth Comment [S8]: A stroke is the rapid loss of brain function due to disturbance in the blood supply Comment [S9]: the gradual biological impairment of normal function.

3. A dozen species of mole rat exist, all native to sub-Saharan Africa. Naked mole rats stand out, though, not least because they appear completely bald. They are also extremely social, living underground in elaborate networks of tunnels and chambers in groups of up to 300. Here in the lab, Park mimics their burrow system by connecting several dozen plastic boxes with long tubes. The animals spend their days pushing bedding around the tubes and nibbling on bits of sweet potato.

Comment [S10]: living naturally in a particular region Comment [S11]: to be prominent or special Comment [S12]: To copy or imitate closely Comment [S13]: Take small bites

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Page 2 of 16 Paragraph 3 SAQ7. Explain why the mole rat populations may be termed as endemic. This is because all species of mole rats are found in sub-Saharan Africa alone. SAQ8. Potato contains a lot of starch. Suggest the importance of potato in the diet of mole rats. Starch can be digested by the mole rat to produce glucose. The glucose is a good respiratory substrate. SAQ9. Explain what is meant by a population. All the organisms of a single species living in a particular habitat.

SAQ10. Explain how a dozen species may have arisen from a single species of mole rat. Populations of mole rats may have become isolated, either by geographical barriers or differences in behavior. This isolation would prevent gene flow and different selection pressures on each population would cause genetic drift. The gene pools will diverge from each other and may become so different that the populations lose their ability to interbreed and produce fertile offspring. This gives rise to several species. SAQ11. Apart from the inability to interbreed, state one other method that scientists could use to identify different species. DNA hybridization, proteomics or DNA fingerprinting. 4. Naked mole rats are a really odd mammal species, Park tells me. Their social structure is like that of insects. Akin to bees and ants, they live in a eusocial society in which a single breeding queen churns out all the offspring, with help from between one and three kings. The rest of the animals work for a living: soldiers defend the colony against predators and rivals, while housekeepers forage for root vegetables and tidy up the tunnels. Paragraph 4 SAQ12. Naked mole rats show various adaptations to their particular environment. Give an example of (a) a behavioural adaptation, (b) a physiological adaptation, and (c) an anatomical adaptation exhibited by these animals. Anatomical Large (incisor) teeth for dealing with tough fibrous plant material and digging Lack of fur and reduced eyes Physiological eg. ability of neurones to tolerate oxygen deprivation Behavioral soldiers defending colony against predators and rivals (instead of running away and saving themselves) SAQ13. The non-reproductive individuals in eusocial animals do not directly transfer their genes to offspring. In spite of this there must still be a genetic advantage in being eusocial suggest what this must be. Non-reproductive naked mole rats share alleles/genes with other members of the colony; By assisting other members of the colony Queen can produce more offspring; This increases chances (of the genes they share) being inherited; SAQ14. Suggest one disadvantage of a single female producing all the offspring in the colony. This could decrease the biodiversity of the population, as there will be less heterozygosity or genetic diversity in the offspring. This could make the population less adaptable and vulnerable to environmental change. SAQ15. How is genetic variation brought about? Mutations, crossing over, random assortment of chromosomes and random fusion of genetically variable gametes. SAQ16. Explain what is meant by the term Niche. A niche is the role played by an organism in its ecosystem, or, the way an organism utilizes the resources in an environment. SAQ17. Soldier, housekeepers, Kings and Queen are anatomically and physiologically different. This difference may be due to differential gene expression. Explain what is meant by differential gene expression. Specific genes are switched on, while other genes are switched off. The genes that are switched on produce specific mRNA. The mRNA produces specific polypeptides by translation. These proteins determine the structure and function of cells and the organism. SAQ18. Suggest the advantage of defending the colony from rivals. This will help to reduce competition for resources and increase the chances of survival of organisms in the colony. SAQ19. Explain what is meant by a predator. A predator is an organism that kills and feeds on the flesh of another organisms. 5. Many features of the skin of the naked mole-rat, such as the lack of an insulating layer and the loosely folded morphological arrangement contribute to poikilothermic responses to changing temperatures of this mammal. Further evidence for poikilothermy in the naked mole-rat is indicated by the presence of pigment containing cells in the dermis, rather than the epidermis, as commonly occurs in homeotherms. Lack of fur is compensated by a thicker epidermal layer and a marked reduction in sweat glands.

Comment [S14]: Of similar character Comment [S15]: living in a cooperative group in which usually one female and several males are reproductively active and the non-breeding individuals care for the young or protect and provide for the group Comment [S16]: the process of bearing offspring; reproduction Comment [S17]: breeding female Comment [S18]: to produce something in large quantities quickly Comment [S19]: males that mate with the queen Comment [S20]: a carnivorous animal that hunts, kills, and eats other animals in order to survive Comment [S21]: group that competes Comment [S22]: somebody who takes care of his or her own house and its residents Comment [S23]: the process of searching for something, especially a search for food and supplies

Comment [S24]: The form and structure of an organism or one of its parts Comment [S25]: having a body temperature that varies according to the temperature of the local atmosphere Comment [S26]: the thick sensitive layer of skin or connective tissue beneath the epidermis Comment [S27]: the thin outermost layer of the skin, itself made up of several layers, that covers and protects the underlying dermis Comment [S28]: an organism whose stable body temperature is generally independent of the temperature of its surrounding environment

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Page 3 of 16 Paragraph 5 SAQ20. Melanin is a pigment found in the skin and fur of mammals. Explain the environmental influence on the phenotype with reference to melanin production. High exposure to UV radiation stimulates the increased production of Melanocyte Stimulating Hormone (MSH) and MSH receptor on melanocytes. This triggers the increased production of melanin. The melanin is packed into melanosomes and transferred to other epidermal cells. This protects the nuclei from UV damage and reduces mutations in DNA. SAQ21. Give two examples of features that help thermoregulation in most mammals that are reduced or absent in Naked Mole rats and explain how each operates to help achieve thermoregulation. Sweat glands; Secretion of sweat onto skin removes heat by evaporation; Fur; Creates insulating layer of trapped air; SAQ22. Give one advantage and one disadvantage in being poikilothermic in comparison to homeothermy. Advantage reduced energy consumption; Disadvantage metabolic activity will change with change in environmental temperature; Poikilothermic animals will be less active if environmental temperature falls; SAQ23. Explain how the skin of humans acts as an insulating layer. It has adipose tissue, which reduces heat loss. SAQ24. State the function of the skin in prevention of infection.
The keratinized closely packed epithelial cells in human skin acts as a physical barrier to pathogens.

6. This unusual social arrangement is what first drew scientists to study the wrinkled rodents. For many years, most of the studies were on their behaviour, says Rochelle Buffenstein, a physiologist at the University of Texas Health Science Center in San Antonio. In time, though, researchers couldnt help but notice another intriguing aspects of naked mole rat biology. They are incredibly longlived creatures, she says. Paragraph 6 SAQ25. Suggest the advantage of stating the credentials of a Rochelle Buffenstein ( physiologist at the University of Texas Health Science Center in San Antonio). This is to acknowledge the source of information and allows readers to assess the credibility of the source. 7. In general, lifespan tends to correlate with body size. Large animals, on average, live longer than small ones. However, while mice and rats are lucky to survive three years in captivity, similar-sized naked mole rats live three decades, making them the longest-lived rodents on Earth. Thats not all. They also maintain excellent health well into their sunset years. Their bones remain strong, their bodies stay fit and they dont show signs of heart disease or mental decline. Breeding females continue to produce pups right up to the end and, to top it off, naked mole rats dont even get cancer. Paragraph 7 SAQ26. What evidence would scientists look for when searching for evidence of heart disease in naked Mole Rats? Damage to coronary artery; Presence of atherosclerosis/atheroma (in wall of arteries) SAQ27. "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. 1. Correlation does not necessarily mean causation. 2. In general - if size caused the lifespan to change, then the statement would always be true. 3. Not enough data may have been collected to prove that the correlation is a causation. SAQ28. Suggest how the conclusions of the investigations conducted could be accepted by the scientific community. 1. Publish results in scientific journals 2. Present results at conferences 3. Peer review 4. Any explanation for peer review (e.g. scientists in the same field conduct the experiment to check its validity whether the results are similar) SAQ29. State two disorders that could lead to mental decline and state the main cause for each. Parkinsons disease caused due to lack of dopamine in the frontal cerebral cortex and Depression, caused due to lack of serotonin in the limbic system of the brain. 8. Naturally, scientists are eager to understand the secrets of this small, bald Methuselah. Buffenstein, who has been studying naked mole rats for 30 years, is among those looking for molecular explanations for their astounding longevity. She began by investigating their response to oxidative stress, one of the leading theories of how the ageing process works. Paragraph 8 SAQ30. State the main features for the study to investigate the effect of oxidative stress on ageing. Large sample size; suitable duration; control group (not exposed to oxidative stress); experimental group (exposed to oxidative stress); difference in results compared.

Comment [S29]: a line or crease between small folds of skin that forms on the face as a result of aging Comment [S30]: a biologist specializing in physiology, the biological study of the functions of living organisms and their parts. Comment [S31]: fascinating

Comment [S32]: Have a mutual relationship Comment [S33]: 30 years Comment [S34]: Old age

Comment [S35]: Methuselah is purported to be the oldest person to ever live (969yrs). Comment [S36]: stunning Comment [S37]: the length or duration of life Comment [S38]: Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily repair the resulting damage.

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Page 4 of 16 9. According to this theory, oxygen-containing free radicals damage the molecules of the body, causing them to deteriorate over time until they stop functioning altogether. This oxidative damage, as it is known, is apparent as extra molecules that attach to DNA and proteins like chewing gum stuck to the bottom of a shoe, Buffenstein says. If oxidative stress is truly an important mechanism of ageing, she predicted, naked mole rats should have lower rates of oxidative damage than more short-lived species. Paragraph 9 SAQ31. Describe the structure of DNA. DNA is made up of two polynucleotide chains, which are anti-parallel to each other. The chains are held to each other by Hydrogen bond between nitrogenous base pairs. The two chains are then coiled into a double helix.
Comment [S39]: a highly reactive atom or group of atoms with an unpaired electron Comment [S40]: become worse

SAQ32. Describe the tertiary structure of proteins. The tertiary structure of a protein is the complex three - dimensional globular shape the polypeptide chain takes when the polypeptide chain twists and folds around itself. The tertiary structure is maintained by Hydrogen bonds, disulphide bridges [covalent bonds] and ionic bonds between the Residual groups of amino acids. Hydrophobic interactions also help to maintain the shape of globular proteins, like enzymes and trans-membrane proteins. The specific three dimensional shape [secondary, tertiary, quaternary structure] of a protein is maintained by three types of chemical bonds between the Residual groups of amino acids Hydrogen bonds: form between some Hydrogen atoms [which bear a slight positive charge] and oxygen and nitrogen atoms [which bear a slight negative charge]. Although these bonds are weak, the large number of bonds provide a considerable force to maintain the three dimensional shape. Ionic bonds: form between carboxyl [COOH] groups and amino [NH2] groups found in the Residual chains. They are stronger than H bonds, but can be broken by changes in pH and high temperature Disulphide bonds: Some amino acids, like cysteine and methionine contain sulphur atoms in the Residual groups. Disulphide bonds can form between sulphur atoms of amino acids that are close together. These bonds are strong and contribute to the strength of structural proteins like collagen. They are also useful in linking the two polypeptide chains of insulin together.

Hydrophillic and hydrophobic interactions of the Residual groups also influence the tertiary structure.

SAQ33. Suggest how extra molecules attaching to proteins might affect their structure and function. (extra molecules) affect bonding that maintains the tertiary structure; Bonds between R groups are changed/broken; Ref to named bond eg disulphide, hydrogen, ionic, Tertiary structure shape is changed;
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Page 5 of 16 10. To her surprise, Buffenstein found the opposite: more telltale oxidative damage in 6-month-olds than in mice of the same age. Remarkably, however, the damage had no obvious impact on their well-being. Keeping in shape 11. Why is this? To find out, Buffenstein took a closer look at the 3D structure of proteins, which is critical to their functioning. Mouse proteins begin misfolding very quickly after suffering oxidative damage a kind of anti-origami that causes them to stop working properly. But naked mole rat proteins can withstand significantly more damage before they lose their shape (Proceedings of the National Academy of Sciences, vol 106, p 3059). We think [protein stability] is a very important component of their extraordinary longevity, she says. If your proteins maintain their integrity, if they have the mechanisms to protect themselves, it doesnt matter what stress comes along. Paragraph 11 SAQ34. Using your knowledge of tertiary structure of proteins, suggest why some proteins may be more prone to oxidative damage than others. Since oxidative damage is caused by free radicals, the free radicals result in damage to polypeptides by neutralizing charged Residual groups. This can cause denaturation of proteins by disrupting Hydrogen and ionic bonds and hydrophobic and hydrophilic interaction. Proteins which have more covalent bonds will be more stable than proteins with more ionic or hydrogen bonds. SAQ35. Describe what is meant by allosterism and state one process where allosterism plays a role. Allosterism is a process whereby a protein changes its shape when it binds to another molecule. The induced fit hypothesis of enzyme action and carrier proteins changing shape to transmit substances across the membrane, are examples of allosterism. SAQ36. Apart from oxidative stress, state three other factors which can influence protein structure. pH, temperature and inhibitors. 12. Another factor that helps naked mole rats reach an advanced age is their remarkable ability to avoid cancer. Nearly all mice have cancerous cells lurking in their bodies by the time they die but cancer has never been seen in a naked mole rat. Every time one of our animals die, we try to figure out what they die of, Buffenstein says. We havent seen a tumour, we havent seen lesions, we havent seen signs of lymphoma. We know they dont get age-related cancer. Paragraph 12 SAQ37. Suggest what processes would be altered by the cancer causing genes. Rate of mitosis; Apoptosis /programmed cell death 13. To understand why, Buffenstein and her colleague Peter Hornsby introduced cancer-causing genes into cells from rats, mice, humans and naked mole rats. They then inserted the altered cells into immune-compromised mice. In two to four weeks, the mice injected with modified cells from rats, mice and humans developed highly invasive tumours. In the case of naked mole rats, six months lapsed and there were still no tumours, Buffenstein says. Paragraph 13 SAQ38. Describe the techniques that would be used to insert the cancer causing genes into the cells of rats. Use of vector; named vector (eg virus/liposome); description of technique of identifying modified cells (eg antibiotic resistance). SAQ39. How might the immune system of immune compromised mice differ from normal mice. Any named part of the immune system e.g fewer T helper cells, fewer plasma cells; Consequence given eg. fewer T helper cells mean less activation of B cells and less antibody production. SAQ40. Suggest why the mice that received the genetically modified cells had to be immunocompromised. The glycoprotein and protein molecules (antigens) on human and rat cells will differ from the molecules on the mice cells. The immune system of the mice will recognise these cells as nonself and trigger an immune response to destroy these cells. 14. The abnormal cells were still alive but had stopped replicating. We think mole rats have better surveillance mechanisms to assess whats going on in their DNA, she says. When things go awry, the deviant cells are essentially locked away, unable to replicate and cause tumours (Aging Cell, vol 9, p 626). Paragraph 14 SAQ41. Name the process by which cells replicate (p14) and describe the events that take place in the main events of this process. Mitosis SAQ42. Suggest the process by which deviant cells may be locked away or prevented from replication. Differential gene expression. The genes for cell division in these cells are permanently switched off. 15. This is probably just one of several tricks that allow these animals to avoid cancer. Another possible mechanism being investigated centres on how cells multiply. When cultured in a Petri dish, cells
Author of A Level biology text books and practical workbooks, global academic consultant and Head of Institution, Republic of Maldives.

Comment [S41]: traditional Japanese art of paper folding Comment [S42]: The state of being unimpaired; soundness

Comment [S43]: an abnormal new mass of tissue that serves no purpose Comment [S44]: A region in an organ or tissue that has suffered damage Comment [S45]: Cancer of the lymph nodes

Comment [S46]: Co-worker Comment [S47]: a state in which the immune system's ability to fight infectious disease is compromised or entirely absent Comment [S48]: progressive spread of disease from one organ in the body to another Comment [S49]: passed

Comment [SVR50]: close watch kept over someone or something Comment [SVR51]: Out of the normal or correct position Comment [SVR52]: Cells which have come to differ from normal cells

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Page 6 of 16 from both mice and humans multiply until they form a single dense layer. At that point, they stop dividing, halted by a process called contact inhibition. In cancerous tissues, however, the abnormal cells continue to multiply, piling up and growing out of control. Paragraph 15 SAQ43. State three physical conditions that must be controlled while culturing cells in a Petri dish to ensure rapid growth. Temperature, Nutrients, pH, Oxygen SAQ44. Explain why it is necessary to maintain aseptic conditions in cell cultures. To prevent bacteria from destroying the cells and to reduce competition for nutrients between the cells and the bacteria. 16. We think weve found the reason these mole rats dont get cancer, and its a bit of a surprise, says Vera Gorbunova, associate professor of biology at the University of Rochester and lead investigator on the discovery. 17. Naked mole rats can live up to 30 years, which is exceptionally long for a small rodent. Despite large numbers of naked mole-rats under observation, there has never been a single recorded case of a mole rat contracting cancer, says Gorbunova. Adding to their mystery is the fact that mole rats appear to age very little until the very end of their lives. 18. Over the last three years, Gorbunova and Andrei Seluanov, research professor of biology at the University of Rochester, have worked an unusual angle on the quest to understand cancer: Investigating rodents from across the globe to get an idea of the similarities and differences of how varied but closely related species deal with cancer. SAQ45. Explain what is meant by a species. A species is a group of organisms which can interbreed to produce fertile offspring. 19. In 2006, Gorbunova discovered that telomerase an enzyme that can lengthen the lives of cells, but can also increase the rate of cancer is highly active in small rodents, but not in large ones. Paragraph 19 SAQ46. Describe the structure of an enzyme. All enzymes are globular soluble proteins with a tertiary structure. SAQ47. State three factors which can influence the rate of enzyme activity. Enzyme concentration, substrate concentration, pH, temperature and inhibitors. 20. Until Gorbunova and Seluanovs research, the prevailing wisdom had assumed that an animal that lived as long as we humans do needed to suppress telomerase activity to guard against cancer. Telomerase helps cells reproduce, and cancer is essentially runaway cellular reproduction, so an animal living for 70 years has a lot of chances for its cells to mutate into cancer, says Gorbunova. A mouses life expectancy is shortened by other factors in nature, such as predation, so it was thought the mouse could afford the slim cancer risk to benefit from telomerases ability to speed healing. Paragraph 20 SAQ48. Cancers is the result of an interaction between genotype and the environment. Justify this statement. Cancer occurs when the rate of cell multiplication is faster than the rate of cell death. This causes the growth of a tumour. Cancer is caused by environmental damage to DNA from physical factors such as UV light and asbestos chemical carcinogens such as those in the tar in cigarette smoke viruses may trigger cancer by altering the DNA (They transfer oncogenes from one individual to another). Chemicals called radicals are produced by the cell metabolism and can damage DNA. Fresh fruit and vegetables contain antioxidants to destroy radicals. The cause may also be genetic. About 5% of cancers are due to an inherited gene. The progression through the cell cycle (G1, S, G2, M) is controlled by: Oncogenes code for the proteins that stimulate the transition from one stage in the cell cycle to the next. Mutations in these genes can lead to the cell cycle being continually active. This may cause excessive cell division, resulting in a tumour. Tumour suppressor genes produce suppressor proteins that stop the cycle. Mutations inactivating these genes mean there is no brake on the cell cycle and control is lost. One example of a tumour suppressor protein is p53. This protein stops the cell cycle by inhibiting the enzymes at the G1/S transition, preventing the cell from copying its DNA. In cancer cells a lack of p53 means the cell cannot stop entry into the S phase. Such cells have lost the control of the cell cycle. Loss of tumour suppressor proteins has been linked to skin, colon, bladder and breast cancers. If tumours are not removed, cancer cells can spread to other parts of the body through the blood and lymphatic systems. This is called metastasis. SAQ49. Describe the events in the eukaryotic mitotic cell cycle. The cell cycle refers to the changes in the cell structure and function during its life span. The stages of the cell cycle are described below.
Comment [SVR56]: existing Comment [SVR57]: accumulated knowledge Comment [SVR58]: limit the effect

Comment [SVR53]: acquired Comment [SVR54]: the quality of being strange, secret, or puzzling Comment [SVR55]: a search for something, especially a long or difficult one

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Page 7 of 16 a). G1 (First Gap phase): During this stage there is rapid synthesis of RNA and proteins and rapid cell growth occurs during this phase. The cell has only one copy of the genome. b). Synthesis (S) phase: DNA replication occurs. The quantity of DNA doubles in the cell. Nucleus usually gets larger during this stage. The cell now has two copies of the genome. c). G2 (Second Gap) phase: During this phase the cell will continue to grow and produce new proteins. Mitochondria and chloroplasts divide. Energy stores increase in preparation for mitosis.

Fig. 3.1 The cell cycle showing the relative durations of the stages in chromosome duplication and separation (Mitosis) and cell d). M (Mitosis) phase: Nuclear division division (cytokinesis) occurs in four stages - prophase, metaphase, anaphase and telophase. e). C (Cytokinesis) phase: Equal distribution of DNA, organelles and cytoplasm into daughter cells.

SAQ50. Explain what is meant by a mutation. A random change in a gene or chromosome resulting in a new trait or characteristic that can be inherited. Mutation can be a source of beneficial genetic variation, or it can be neutral or harmful in effect. SAQ51. Telomerase could beneficial as well as harmful. Suggest one benefit and one risk of high telomerase activity. Telomerase speeds up cell division. High telomerase activity is beneficial in wound healing. However, extremely high telomerase activity can lead to uncontrolled cell division and lead to cancer. SAQ52. Predation is a biotic factor. What is meant by a biotic factor? Name two other biotic factors. A biotic factor is a factor involving living organisms. Competition and parasitism are two other biotic factors. 21. While the findings were a surprise, they revealed another question: What about small animals like the common grey squirrel that live for 24 years or more? With telomerase fully active over such a long period, why isnt cancer rampant in these creatures? 22. Gorbunova sought to answer that question, and in 2008 confirmed that small-bodied rodents with long lifespans had evolved a previously unknown anti-cancer mechanism that appears to be different from any anticancer mechanisms employed by humans or other large mammals. 23. At the time she was not able to identify just what the mechanism might be, saying: We havent come across this anticancer mechanism before because it doesnt exist in the two species most often used for cancer research: mice and humans. Mice are short-lived and humans are large bodied. But this mechanism appears to exist only in small, long-lived animals. Paragraph 23 SAQ53. Explain why large bodied animals need a well developed circulatory system. The single celled organisms exchange food, respiratory gases and excretory products from the environment, directly from the cell surface membrane. However, animals are multicellular and have a very low surface area to volume ratio and high diffusion distance from the surface to the body core. Diffusion from the body surface would be too slow to supply or remove materials from the cells at a suitable rate to sustain metabolism in these cells. So, multicellular organisms need a circulatory system to supply or remove materials from the cells at a rapid rate. SAQ54. Describe the relationship between body size and heat loss. Larger organisms lose heat slowly. Smaller organisms lose heat more rapidly. 24. Now, Gorbunova believes she has found the primary reason these small animals are staying cancer free, and it appears to be a kind of overcrowding early-warning gene that the naked mole rat expresses in its cells. Paragraph 24 SAQ55. Explain how transcription factors bring about expression of a gene (p24) Attach to promoter region next to gene; Allow attachment of RNA polymerase; SAQ56. Describe the procedures a potential new anti-cancer therapy would have to go through before it could be licenced as a drug. Animal testing; independent review; 3 stage clinical trials; correct description of double blind/placebo/randomisation;

Comment [SVR59]: happening in an unrestrained manner

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Page 8 of 16 25. When Gorbunova and her team began specifically investigating mole rat cells, they were surprised at how difficult it was to grow the cells in the lab for study. The cells simply refused to replicate once a certain number of them occupied a space. Other cells, such as human cells, also cease replication when their populations become too dense, but the mole rat cells were reaching their limit much earlier than other animals cells. Paragraph 25 SAQ57. Stem cells can be cultured in a Petri dish. State what is meant by totipotent and pluripotent stem cells. Totipotent stem cells can differentiate into all cell types, including extra-embryonic cell types. However, pluripotent stem cells can differentiate into most cell types, but not extra-embryonic cell types. 26. Since cancer is basically runaway cell replication, we realized that whatever was doing this was probably the same thing that prevented cancer from ever getting started in the mole rats, says Gorbunova. 27. Like many animals, including humans, the mole rats have a gene called p27 that prevents cellular overcrowding, but the mole rats use another, earlier defense in gene p16. Cancer cells tend to find ways around p27, but mole rats have a double barrier that a cell must overcome before it can grow uncontrollably. Paragraph 27 SAQ58. Genes are commonly referred to by their loci. State what is meant by a gene locus. A gene locus refers to the location of a gene on a chromosome. Every gene occupies a specific locus. SAQ59. How can one gene give rise to more than one protein? (Post-transcriptional modification; Mutations) SAQ60. Naked mole rats have a gene (P16) which halt cell replication at an earlier stage than in humans. Name and Explain a mechanism by which this gene could be delivered into cancerous cells? (Gene therapy) 28. We believe the additional layer of protection conferred by this two-tiered contact inhibition contributes to the remarkable tumor resistance of the naked mole rat, says Gorbunova in the PNAS paper. 29. Gorbunova and Seluanov are now planning to delve deeper into the mole rats genetics to see if their cancer resistance might be applicable to humans. Paragraph 29 SAQ61. Conservation involves maintenance of high genetic diversity in populations. It also helps to save species from extinction. Apart from the ethical obligation we have to save species from extinction, use the information in line paragraph 29 to suggest another advantage of saving species from extinction. Many species, however insignificant they may appear, may have genes that could help cure human ailments or be beneficial to humans for production of economically useful products by genetic engineering. 30. This finding could be an important step towards new cancer therapies. Gorbunova and her colleagues are now trying to decipher the extracellular signals that prompt early contact inhibition. In theory, such a signal might be co-opted to stimulate the process in human cells, and prevent tumours from forming. If this is some kind of extracellular molecule, then we could actually apply it to people as an injection or a drug, she says. Paragraph 30 SAQ62. Explain how extracellular signals that prompt early contact inhibition operate. Transcription of a gene is initiated by RNA polymerase and transcription factors binding to a promoter region (section of DNA upstream to a gene). RNA Polymerase + Transcription factors = Transcription Initiation Complex Some transcription factors are always present in all cells (example the transcription factors needed to switch on the genes for respiration or protein synthesis). Other transcription factors are only synthesised in certain cells at a particular stage of development, often in an inactive form, which is later activated by signal proteins or regulator proteins. Signal proteins may act directly by entering the cell (like steroid hormones) or indirectly through a second messenger (cAMP). The gene is switched on when all the transcription factors, in their active form, are present. Switching off a gene deactivation Genes are switched off (not able to be transcribed) by the cell protein repressor molecules may attach to the promoter region, hence blocking the attachment sites for transcription factors. protein repressor molecules can attach to the transcription factors preventing them forming the transcription initiation complex. signal proteins (Hormones) acting as transcription factors may not be present. promoter may not be accessible to the transcription factors or RNA polymerase. Every transcription initiation complex has a range of different factors with some acting as activators and others repressing expression. The exact order in which these factors bind is not known with certainty. In some experiments the transcription factors seem to bind in a specific order. In other cases, most of the factors are thought to first assemble with the polymerase, with this whole assembled complex then binding to the DNA in a single step. The number of transcription factors found within an organism increases with the size of the genome. There are thought to be approximately 2600 proteins in humans that can bind to DNA. If most of these function as transcription factors then about 10% of our genes must code for transcription factors. This
Author of A Level biology text books and practical workbooks, global academic consultant and Head of Institution, Republic of Maldives.

Comment [SVR60]: uncontrolled

Comment [SVR61]: to give something such as an honour to someone Comment [SVR62]: layered Comment [SVR63]: Research or make painstaking inquiries into something

Comment [SVR64]: treatment of physical, mental, or behavioral problems that is meant to cure or rehabilitate somebody Comment [SVR65]: a person somebody works with, especially in a professional or skilled job Comment [SVR66]: decode

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Page 9 of 16 makes transcription factors the largest group of human proteins. The general transcription factors have been highly conserved in evolution, with the same factors occurring in different organisms from humans to simple single-cell organisms. Mammalian hormones are chemical messengers carried by the blood from endocrine glands to all parts of the body. They affect specific cells, called target cells. Many hormones activate transcription factors in the target cells. Chemically hormones are of three types: Amines: - Adrenaline / Thyroxine (Lipid insoluble, so cannot enter the cell). Peptides/Proteins: - Insulin / Glucagon (Lipid insoluble, so cannot enter the cell). Steroids: - Oestrogen / Testosterone (Steroids are lipid soluble and can enter the cell). The mode of action for peptide hormones and steroid hormones is entirely different.

Fig. 7.1 A peptide hormone 1. Hormone binds to specific receptor on the cell membrane. 2. Adenyl cyclase enzyme is released from the receptor and diffuses into the cytoplasm. 3. Adenyl cyclase converts ATP into cyclic AMP (Second messenger) 4. The second messenger initiates a series of reactions in the cell and activates Transcription Factor 7,in this case. 5. The activated transcription factor (TF7) now binds to the existing Transcription factors (TF1 to TF6, in this case) and completes the Transcription Initiation Complex. This activates RNA polymerase to become active and begin the process of transcription of the gene. The gene is now SWITCHED ON. .......................................................................................................................................................................

Fig. 7.2 A steroid hormone 1. Steroid hormone binds to specific receptor on target cell and enters the cytoplasm, as the membrane is permeable to steroid hormones, like testosterone or oestrogen. 2. The steroid hormone will bind to a transcription factor in the cytoplasm. 3. The transcription factor and the hormone bind to other transcription factors (TF1 to TF6, in this case) and complete the formation of the Transcription Initiation Complex. 4. The formation of the Transcription Initiation Complex ensures that the gene is SWITCHED ON. 5. Transcription of the gene begins and mRNA is formed. 31. Exciting as that research may be, cancer and ageing are only the tip of the iceberg as far as the naked mole rats peculiar biology is concerned. The rodents neurobiology is also of interest, as Park is discovering. Setting out to better understand their sense of touch, he stumbled across something surprising: they lack a receptor that transmits messages about chemical pain. Inject lemon juice or the essence of chilli pepper, capsaicin, beneath the skin of a mouses paw, an d it will shake and lick it like crazy. If you do that with naked mole rats, they dont do anything, Park says. They couldnt care less. Naked mole rats do feel acute pain such as cuts and burns, he says, but they are impervious to chemical pain (PLoS Biology, vol 6, p e13). Paragraph 31 SAQ63. Explain how impulses would be transmitted from the pain receptors of a rodent to its central nervous system. Through sensory neurone; as action potential/ wave of depolarisation/; ref to influx of sodium ions into neurone; ref to local currents allowing propagation; ref to salutatory conduction; SAQ64. What is the sequence of neurones impulses would pass through, to result in withdrawing a hand from a hot stove. Sensory neurone to relay neurone to motor neurone;

Comment [SVR67]: unusual, strange, or unconventional Comment [SVR68]: to find or come across something by chance

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Page 10 of 16 32. This finding is particularly significant because the nerve fibres associated with chemical pain are also involved in post-traumatic pain in people precisely the type of discomfort researchers would like to eliminate. Its OK to have pain sensation to tell you to get your hand off the stove, or to stop exercising because your knee is in trouble, says Park. But post-surgical pain, or joint pain after a knee injury, those types of pain we could do without. The naked mole rats are laying the groundwork for potentially finding new ways to treat the kinds of pain we dont want. Paragraph 32 SAQ65. State two knee ailments that could result from over-exercise. Describe the possible treatment that may be available for such ailments. 1. Keyhole surgery for treatment of cruciate ligament damage Cruciate Ligament Damage ACL injuries are common, especially if you play sports. The anterior cruciate ligament (ACL), is the most often injured ligament of the 4 ligaments in your knee. It is very painful and can be injured by hyper-extending the knee or twisting your knee inward. This can be caused by: Sudden change of direction, causing a twist in your knee A rapid stop with a change in direction Slowing down while running Landing from a jump Contact or collision causing extreme knee hyperextension When the ACL becomes injured you may hear and feel a "pop" in your knee. In most cases, this is the ligament tearing. If this does happen, be sure to apply the Rest, Ice, Compression, and elevation. Otherwise known as the RICE technique. Fig. 9.2

Comment [SVR69]: Post-traumatic stress disorder (PTSD) is a real illness. You can get PTSD after living through or seeing a traumatic event, such as war, a hurricane, rape, physical abuse or a bad accident. Comment [SVR70]: used to indicate that something is stated exactly Comment [SVR71]: basic preparatory tasks that form a foundation for something else

The patient is given anaesthesia, small punctures are made into the knee joint. A small camera and small instruments on the end of long narrow tubes, introduced into the knee through small incisions (keyholes). Remove all of the existing damaged ACL. This is done with a motorized device which is called a shaver. Fig. 9.3 Skin incisions (cuts) are made and the patellar tendon is identified. A slice of the tendon is harvested with a bone block at each end of the tendon. This slice of tendon is called the graft. The advantage of using the persons own tissue is that there will be no tissue rejection. The tissue is taken from around the knee joint, so that the procedure can be completed with a single surgery. Fig. 9.4 Tunnels are drilled into the femur and tibia. The bone plugs of the graft will fit into these tunnels. The graft is then placed through the tibia, through the knee joint, and into the femoral drill hole. Screws, staples or sutures are used to fix the bone plugs. The biological screws will dissolve in about two years. Tendons are less elastic than ligaments. So physiotherapy will be needed to gently stretch the tendons and regain full movement. Overstretching must be avoided to prevent damage to the tendon.

Fig. 9.5 2. Osteoarthritis due to wearing-away of cartilage. Over-training and sports injuries can result in greater wear and tear which may damage the cartilage in the knee joints and lead to osteoarthritis.

Fig. 9.6
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Page 11 of 16 Osteoarthritis is a joint disease that affects the cartilage. In osteoarthritis, the surface layer of cartilage breaks down and wears away. This allows bones under the cartilage to rub together, causing pain, swelling and loss of motion of the joint. Over time, the joint may lose its normal shape. Also, bone spurs small growths called osteophytes may grow on the edges of the joint. Bits of bone or cartilage can break off and float inside the joint space. This causes more pain and damage. Osteoarthritis is common in knee joints because they are the bodys primary weight-bearing joints. Healthy cartilage covering the ends of the bones allows bones to glide over one another, and it absorbs energy from the shock of physical movement. Repetitive load-bearing can cause damage to the cartilage lining the joint. Sudden twisting and excessive force can cause injury to the cartilage, or this can take place over time with repeated use. As cartilage is not supplied with blood, it is very slow to repair itself when damaged. Once the cartilage is damaged, the protection it gives the joint decreases. This can lead to more rapid degeneration, resulting in osteoarthritis.

Fig. 9.7 Fig. 9.8 Keyhole surgery can be used to remove pieces of bone (bone debris) from the joint. Prosthesis A prosthesis is a device designed to replace a missing part of the body, or to make a part of the body work better. For many years, the most successful treatment for severe arthritis of the knee has been total knee replacement. This means removing all the surfaces of both compartments and replacing them with a metal implant on the lower end of the femur and a plastic surface on the tibia.

Fig. 9.10 Fig. 9.9 33. Though the applications are intriguing, Parks own interests are more basic: why would naked mole rats lack this type of pain? The answer, he suspected, stemmed from their unusual habitat. Although many animals live underground, few live in such close quarters and in such large numbers as naked mole rats. The air in their burrows is rank, with low oxygen levels and extremely high levels of carbon dioxide. While normal air is about 0.03 per cent CO2, levels in naked mole rat burrows can easily reach 5 per cent or more an intensity that would sting our eyes and noses and leave us gasping for air. The rodents, however, are unaffected. They will stay away from 10 per cent CO2, but theyre perfectly happy to wallow around in 5 per cent, Park says. It turns out that high levels of CO2 affect the types of nerves that the naked mole rats have disconnected, he says. I think thats the evolutionary driving force to disconnect these pain nerves. Paragraph 33 SAQ66. Describe the responses that humans would show if they were breathing air with 5% Carbon dioxide, and explain how these responses are brought about. Ventilation rate would increase; Rise in CO2/fall in pH detected by receptor; receptor identified as aortic/carotid body/medulla; more impulses sent from ventilation centre; to diaphragm /intercostal muscles; SAQ67. A brain deprived of oxygen will lead to a brain deprived of ATP/energy. Describe the role of oxygen in the production of ATP. Final acceptor of hydrogen at end of electron transfer chain; (by removing H) allows proton gradient/chemiosmosis to continue; without oxygen Krebs cycle and electron transport would cease; SAQ68. With reference to the human brain, explain how the environment may play a role in brain development with regard to critical window periods. Development of neurons in the visual cortex of the brain is dependent on stimuli from the environment. If a child has his or her eyes covered from birth, then the neurons may never
Author of A Level biology text books and practical workbooks, global academic consultant and Head of Institution, Republic of Maldives.

Comment [SVR72]: Arouse the curiosity or interest of Comment [SVR73]: Came from

Comment [SVR74]: to lie down and roll around in something Comment [SVR75]: Selection pressure

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Page 12 of 16 develop to be functional and the child will be permanently blind. This was also well demonstrated by using kittens and monkeys as models to demonstrate the critical window period in the development of vision. 34. This isnt the only effect the naked mole rats burrows have on their physiology. The low oxygen levels are just as important. Fresh air contains about 21 per cent oxygen, whereas levels in the burrows can be as low as 12 per cent in captive colonies, and are probably much lower in the wild. Park has found that naked mole rat brains are incredibly resistant to oxygen deprivation, with their brain tissue able to bounce back after 30 minutes without the gas (NeuroReport, vol 20, p 1634). Paragraph 34 SAQ69. Using your knowledge of the respiratory pathways, explain why ATP production decreases when oxygen is low in the tissues. NADH2 is a hydrogen carrier. It carries oxygen from intermediate compounds in the respiratory pathway to the Electron Transport Chain in the inner mitochondrial membrane. Oxygen is used as the final electron carrier and keeps the electron transport chain operating. Without oxygen, the electron transport chain will stop functioning and NAD cannot be regenerated. Without NAD glycolysis and Krebs cycle cannot function and respiration stops. SAQ70. Explain how populations of Naked Mole rats have evolved to be resistant to hypoxia. Identification of selection pressure is living in a low oxygen environment; Genetic variability in ability to withstand low oxygen exists in mole rats; due to mutation; mole rats that can withstand low oxygen more likely to survive and reproduce (accept converse); alleles for withstanding hypoxia increase in the population; 35. Two University of Illinois at Chicago researchers report that adult naked mole rat brain tissue can withstand extreme hypoxia, or oxygen deprivation, for periods exceeding a half-hour much longer than brain tissue from other mammals. 36. The findings may yield clues for better treatment of brain injuries associated with heart attack, stroke and accidents where the brain is starved of vital oxygen. Paragraph 36 SAQ71. Use of modern scanning techniques has transformed our understanding of the localisation of function in the brain. Describe how fMRI can be used to study brain function and compare this with early techniques that were used to investigate brain function. fMRI follows uptake of oxygen in active brain areas; brain activity results in increased demand for oxygen so increase in oxyhaemoglobin; allows researchers to identify regions of the brain involved in particular tasks; early techniques study of the effect of injury/ animal experiments eg insertion of electrodes/ study of the effect of drugs; 37. John Larson, associate professor of physiology in psychiatry, and Thomas Park, professor of biological sciences, studied African naked mole rats small rodents that live about six feet underground in big colonies of up to 300 members. The living is tight and the breathing even worse, with the limited air supply low in oxygen. 38. But naked mole rats studied were found to show systemic hypoxia adaptations, such as in the lungs and blood, as well as neuron adaptations that allow brain cells to function at oxygen and carbon dioxide levels that other mammals cannot tolerate. SAQ72. Name one type of muscle cell that is specially adapted for anaerobic conditions. State features of these cells that enable them to be tolerant to anaerobic conditions. Fast twitch fibres need a rapid supply of ATP. The aerobic pathway is too long and involves too many reactions to produce ATP. On the other hand, anaerobic respiration produces ATP during glycolysis only, which is a much shorter pathway and can supply ATP rapidly. Low resistance to fatigue. They tire or cramp up easily due to lactic acid formation. The lactic acid reduces the pH within the muscle cells and inhibits respiratory enzymes. This results in complete lack of ATP leading to muscle cramps. Fast twitch fibres are referred to as white muscle and is light pink in colour. It has very little myoglobin and is adapted for anaerobic respiration. If myoglobin was present in abundance, then the muscle will continue aerobic respiration and the rate of ATP production would be too slow to support rapid contraction. Note: the anaerobic respiration pathway is very short when compared to the aerobic pathway. This enables ATP to be produced very rapidly for muscle contraction. Have few mitochondria as muscles undergo anaerobic respiration, which occurs in the cytoplasm. Have lots of sarcoplasmic reticulum, which release plenty of Ca2+ ions for frequent muscle contraction. Have Lots of glycogen, which is converted into glucose and used instantly for respiration. Note: Conversion of glycogen to glucose, in the liver, and subsequent transfer to the muscles would be too slow to meet the rapid demand for glucose during anaerobic respiration. Have few capillaries, which result in reduced oxygen supply and anaerobic respiration. The pathway for anaerobic respiration is very short (Glycolysis only) and generates ATP rapidly. Have a high concentration of creatine phosphate which reacts with ADP in a single step to form ATP rapidly for muscle contraction.
Comment [SVR76]: reduction of oxygen supply to a tissue below physiological levels despite adequate perfusion of the tissue by blood

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Page 13 of 16

ATPase activity is fast. Helps myosin to re-cock rapidly and bring about another round of contraction rapidly. 39. In the most extreme cases, naked mole rat neurons maintain function more than six times longer than mouse neurons after the onset of oxygen deprivation, said Larson. 40. We also find it very intriguing that naked mole rat neurons exhibit some electrophysiological properties that suggest that neurons in these animals retain immature characteristics. SAQ73. State two differences is structure of immature and mature neurons. Mature neurons are myelinated and more branched, when compared to immature neurons. 41. All mammal fetuses live in a low-oxygen environment in the womb, and human infants continue to show brain resistance to oxygen deprivation for a brief time into early childhood. But naked mole rats, unlike other mammals, retain this ability into adulthood. SAQ74. Using your knowledge of differential gene expression, suggest how human infants change their oxygen tolerance as they grow. Genes used for tolerance to low oxygen environment in the womb get switched off and genes needed for living in an oxygen abundant environment get switched on. 42. We believe that the extreme resistance to oxygen deprivation is a result of evolutionary adaptations for surviving in a chronically low-oxygen environment, said Park. 43. The trick now will be to learn how naked mole rats have been able to retain infant-like brain protection from low oxygen, so we can use this information to help people who experience temporary loss of oxygen to the brain in situations like heart attacks, stroke or drowning, he said. 44. Larson said study of the naked mole rats brain may yield clues for learning the mechanisms that allow longer neuronal survival after such accidents or medical emergencies, which may suggest ways to avoid permanent human brain damage. Sociable by nature 45. Medical benefits may even arise from continuing research into naked mole rat behaviour. Previous studies in voles and other mammals have shown that behaviours such as monogamy and maternal performance can be explained, in part, by genetic differences that influence the patterns of certain hormone receptors in the brain. To find out whether naked mole rats sociability has a genetic factor, Chris Faulkes at Queen Mary, University of London and colleagues compared their brains with those of the solitary cape mole rat. They were looking for receptors that bind to the cuddle chemical oxytocin. The team found that the naked mole rat has far more of these receptors in several brain regions including the nucleus accumbens, an area known as the brains pleasure centre, and assume this is under genetic control (Journal of Comparative Neurology, vol 518, p 1792). Its a good example of a change in a gene giving a change in complex behaviour, says Faulkes. Changes in the oxytocin receptor in humans are associated with certain kinds of autism, he adds, so the finding could have direct implications for humans. SAQ75. The diagram shows a cell membrane with oxytocin receptors. Suggest why oxytocin can only bind to specific cell in the brain.

Comment [SVR77]: continuing a long time

Comment [SVR78]: Monogamy is a form of marriage in which an individual has only one spouse during their lifetime or at any one time Comment [SVR79]: Motherly care for the young

Comment [SVR80]: Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior

Comment [SVR81]: Hormone replacement therapy medications containing female hormones to replace the ones the body no longer makes after menopause used to be a standard treatment for women with hot flashes and other menopause symptoms. Hormone therapy (as it's now called) was also thought to have the longterm benefits of preventing heart disease and possibly dementia. Comment [SVR82]: A circadian rhythm is a roughly 24 hour cycle in the physiological processes of living beings, including plants, animals, fungi and cyanobacteria. In a strict sense, circadian rhythms are endogenously generated, although they can be modulated by external cues such as sunlight and temperature. Circadian rhythms are important in determining the sleeping and feeding patterns of all animals, including human beings. There are clear patterns of brain wave activity, hormone production, cell regeneration and other biological activities linked to this daily cycle. Comment [SVR83]: capable of being done Comment [SVR84]: The branch of medicine or surgery that deals with the production and application of artificial body parts Comment [SVR85]: to cut off (all or part of a limb or digit of the body), as by surgery.

The receptors have a specific shape and will bind to a specific hormone only. Only cells with oxytocin receptors can bind to oxytocin. This is how hormone can affect specific target cells. 46. The possibilities dont end there. Naked mole rats do not experience menopause or osteoporosis, so perhaps they could help researchers develop osteoporosis treatments without the side effects of hormone replacement therapy. And, as they spend 24 hours a day in the dark, naked mole rats dont follow normal circadian rhythms. Studies of their sleep patterns could feasibly help treat disordered sleep in humans. 47. Even their incisors are fascinating. Instead of staying put in their mouths, they grow right through the skin of the lips, something of great interest to prosthetics designers. Traditional prosthetics put pressure on delicate soft tissue causing sores and cell death, so a team led by Gordon Blunn and Catherine Pendegrass at University College London are testing new prosthetics that are attached directly to the bone of an amputated limb. To avoid infection, however, there needs to be a
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Page 14 of 16 permanent seal where the skin meets the metal implant. This is where naked mole rats come in. Understanding the interface between their teeth and skin may help in the development of new coatings or structures that can be applied to the prosthetics. Paragraph 47 SAQ76. Why are the new prosthetics being developed at UCL less likely to damage tissues, and why is there a problem that must be overcome with these prosthetics. (new prosthetics) are bonded to bone, not pressing on soft tissues; there is a risk of infection entering body between prosthetic and skin; SAQ77. Describe the role of the skin as a barrier to infection. The skin is made from 2 layers Outer epidermis layer Inner dermis layer The epidermis provides a physical barrier to invading pathogens, as shown in fig 11.6. There are 2 layers in the epidermis; A - Outer cornified layer, composed of compacted dead dry cells filled with indigestible keratin protein (which also forms nails and hair). The compact closely packed cells prevent entry of pathogens. B - Inner Malpighian layer or basal layer, site of rapid mitosis and keratinisation.

The skin also has chemical defence mechanisms; Sebaceous glands secrete sebum, which is an oily secretion with a pH between 3 to 5. Sweat is also acidic. This makes the skin acidic, inhibiting bacterial growth. Sebaceous glands also secrete the enzyme lysozyme, which is a natural antibiotic. Lysozyme destroys bacterial cell walls. 48. Our current hypothesis is that behavioural interactions between the queen and non-breeders are translated into a suppression of gonadotrophin-releasing hormone in the hypothalamus, which in turn suppresses the release of gonadotrophins from the anterior pituitary. This results in a suppression of ovulation in non-breeding females, while in non-breeding males testosterone concentrations and sperm numbers are lower, and in most males sperm are non-motile. Not only does the queen suppress reproductive function in the non-breeders, but she also apparently exerts some control over the breeding male(s), such that concentrations of testosterone in the latter are suppressed except around the time of ovulation in the queen. Despite these endocrine deficiencies in non-breeders that may persist for many years, the block to reproduction is reversible. Nonbreeding males and females will rapidly become reproductively active if they are removed from the suppressing influences of their colony and housed singly or in male-female pairs, or if the queen in a colony dies. SAQ78. The ineraction between the genes and the environment can influence the phenotype of the organism. Discuss the contribution of nature and nurture in the expression of reproductive behavior in the naked mole rat. Interaction between the queen and the non-breeders (environmental) produces a cascade of hormonal action (genetic) which suppresses ovulation and sperm production (phenotype). If the environment changes and the queen dies or the non-breeders are isolated in male and female pairs then the phenotype changes to fertile individuals. This is a clear example of how the phenotype can be influence by the interaction between the environment and the genotype. SAQ79. State the features of sperms that enable them to carry out their function efficiently.
Comment [SVR86]: a proposed explanation for a phenomenon

Comment [SVR87]: not capable of movement

Fig.4.16 Structure of sperm

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Page 15 of 16 Sperms are produced in large numbers. The advantage of this is: 1. No two sperms are the same, so there is a very high range of genetic variation. 2. Many sperms do not reach egg large numbers will increase chances of reaching the egg. Also if sperm numbers are high then many sperms will release enzymes into the zona pellucida and increase the chance of penetration. 3. Selection for the fittest sperm occurs, because some sperms may be defective and will not be able to reach or penetrate the ovum. Part of Sperm Adapted for Nucleus Head Midpiece (neck) Tail (Flagellum) Acrosome Contains only one copy of each chromosome (haploid) Contains the nucleus and lysosome (acrosome). Contains lots of mitochondria, which make ATP for the sperms to swim. Made from motor proteins and microtubules, which use ATP to propel the sperm forwards A specially modified lysosome in the sperms head. The acrosome swells and bursts when the sperm comes in contact with the follicle cells and zona pellucida. The enzymes in the acrosome digest the follicle cells and the zona pellucida to allow the cell membranes of the sperm and ovum to fuse. Very little cytoplasm, which means cells are small and therefore can be released in large numbers. It also assists motility (movement) of sperms.

Cytoplasm

SAQ80. The queen prevents non-breeders becoming reproductive by altering the hormonal balance in the non-breeders. Compare and contrast the ways in which this kind of communication differs from nervous communication. Hormonal (accept converse for neural if clearly identified) slower acting; longer duration; hormone reaches all cells in body but only affects those with receptors; response can be widespread; controls long term changes such as growth; 49. Patterns of genetic structure in naked mole-rat populations were quantified within and among geographically distant populations using DNA fingerprinting. Individuals within colonies were genetically almost monomorphic, having coefficients of band sharing estimated from DNA fingerprints ranging from 0.93 to 0.99. SAQ81. Describe the techniques and procedures that would be used to produce a DNA fingerprint from a Naked Mole Rat. DNA extracted from cells; Isolation of gene with restriction enzymes; amplification of microsatellite with PCR; use of electrophoresis; detail of electrophoresis agarose gel/electric field/ ref to small fragments moving faster/; ref to southern blotting; ref to use of probe; ref to technique of visualising DNA; SAQ82. Suggest the possible consequences of having coefficients of band sharing estimates from DNA fingerprints ranging from 0.93 to 0.99.

Comment [SVR88]: DNA profiling (also called DNA testing, DNA typing, or genetic fingerprinting) is a technique employed by forensic scientists to assist in the identification of individuals by their respective DNA profiles. Comment [SVR89]: Having one or the same genotype, form, or structure through a series of developmental changes.

This indicates that genetic diversity is very low. This will decrease the chances of survival of the species in a changing environment reduce the ability of the organisms to adapt to various environments. The chances of survival of the species in a changing
environment, is low. 50. Prolonged inbreeding is usually associated with lowered fitness, and it has been shown that most highly inbred small mammals have inbreeding-avoidance mechanisms that promote some degree of outbreeding. Although rare, a dispersive morph exists within naked mole-rat colonies that may occasionally promote outbreeding. These dispersers are morphologically, physiologically and behaviourally distinct from other colony members. They are laden with fat, exhibit elevated levels of luteinizing hormone, have a strong urge to disperse, and only solicit matings with non-colony members. SAQ83. Suggest why out-breeding is likely to increase the long term survival of Naked Mole Rat populations. Increases genetic variation; at least some mole rats will have allele combinations that allow survival in changing environment; prevention of inbreeding depression; 51. Kin recognition and female mate choice using a series of choice tests in which the odour, social and mate preferences of females were determined. Discrimination by females appears to be dependent on their reproductive status. SAQ84. In the suppression of breeding by the queen identify (a) the stimulus (b) the effector and (c) the response for the non-breeding males. Stimulus is behavioural interaction with queen; effector is testis; response is lowered testosterone/ few and non-motile sperm; 52. Reproductively active females prefer to associate with unfamiliar males, whereas reproductively inactive females do not discriminate. Females do not discriminate between kin and non-kin suggesting that the criterion for recognition is familiarity, not detection of genetic similarity per se. In the wild, naked mole-rats occupy discrete burrow systems and dispersal and mixing with nonkin is thought to be comparatively rare. Thus, recognition by familiarity may function as a highly efficient kin recognition mechanism in the naked mole-rat. A preference by reproductively active females for unfamiliar males is interpreted as inbreeding avoidance. These findings suggest that, despite an evolutionary history of close inbreeding, naked mole-rats may not be exempt from the effects of inbreeding depression and will attempt to outbreed should the opportunity arise.
Comment [SVR90]: Inbreeding is reproduction from the mating of parents who are closely related genetically. Inbreeding results in increased homozygosity, which can increase the chances of offspring being affected by recessive or deleterious traits. This generally leads to a decreased fitness of a population, which is called inbreeding depression. Comment [SVR91]: An individual who results from inbreeding is referred to as inbred. Comment [SVR92]: the interbreeding of individuals or stocks that are relatively unrelated, often producing a hybrid of superior quality. Comment [SVR93]: any of the different forms of individual found in a polymorphic species Comment [SVR94]: move away from the colony and thereby promotes outbreeding Comment [SVR95]: to seek for (something) by entreaty, earnest or respectful request, formal application Comment [SVR96]: group of persons descended from a common ancestor

Comment [SVR97]: somebody related by blood Comment [SVR98]: Unrelated Comment [SVR99]: closeness and friendliness in a personal relationship Comment [SVR100]: in itself, by itself, or intrinsically Comment [SVR101]: completely separate and unconnected Comment [SVR102]: to allow or entitle somebody not to do something that others are obliged to do

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Page 16 of 16 SAQ85. Explain what is meant by inbreeding depression. Inbreeding is reproduction from the mating of parents who are closely related genetically. Inbreeding results in increased homozygosity, which can increase the chances of offspring being affected by recessive or deleterious traits. This generally leads to a decreased fitness of a population, which is called inbreeding depression. 53. With so much to offer science, it is no surprise that naked mole rats are becoming more common in labs. Unlike mice, the naked mole rat hasnt yet had its genome sequenced yet. With naked molerats, we have to start from scratch with many things, Gorbunova says. Its not very convenient, but I think its definitely worth it. Paragraph 53 SAQ86. "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)? 1. It can impact the development of new treatments, theories etc. and therefore impact the rate of helping other humans. 2. It is expensive and time-consuming to sequence the genome of the mole-rat. 3. The mole-rats may be more useful in terms of physiology and behaviour than mice. 4. Mole-rats are animals with a nervous system, so may be more unethical to test with (as with mice). 5. Mole-rats live for a relatively long time, so can be studied in the long-term too. 6. 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. SAQ87. From one ethical viewpoint discuss whether some of the experiments carried out on Naked Mole Rats can be justified. Utilitarianism; suffering is restricted to few individuals; mole rats have reduced sensitivity to chemical pain therefore have less capacity to suffer; research on mole rats has very large potential benefits to human health; Acknowledgements Adapted text taken from: Naked and ugly: The new face of lab rats, Kirsten Weir, New Scientist Magazine, 23 October 2010, Issue 2783 Copyright Reed Business Information Ltd Adapted text taken from: University of Rochester (October 26 2009), Scientists Discover Gene That Cancer-proofs Naked Mole Rats Cells, ScienceDaily, retrieved 11 November 2011, from http://www.sciencedaily.com/ releases/2009/10/091026152812.htm Adapted text taken from: A dispersive morph in the naked mole-rat, ORiain, MJ, Jarvis, JUM and Faulkes, CG, Nature 380, 619621 (18 April 1996); doi: 10.1038/380619a0, retrieved 11 November 2011 from: http://webspace.qmul.ac.uk/cgfaulkes/abstract7.html Adapted text taken from: University of Illinois at Chicago (November 30 2009), Naked mole rats may hold clues to surviving stroke, ScienceDaily, retrieved 11 November 2011, from http://www.sciencedaily.com/releases/2009/11/091130141313.htm Adapted text taken from: A Reproductive Dictatorship: The Life and Times of the African Naked MoleRat, http://webspace.qmul.ac.uk/cgfaulkes/CGFNMR.htm Adapted text taken from: Micro- and macrogeographical genetic structure of colonies of naked molerats Heterocephalus glaber, Faulkes, CG, Abbott, DH, OBrien, HP et al. (1997), Mol Ecol vol. 6, (7) 615628, retrieved 11 November 2011, from http://www.ncbi.nlm.nih.gov/pubmed/9226945 Adapted text taken from: Kin discrimination and female mate choice in the naked mole-rat Heterocephalus glaber, Clarke, FM and Faulkes, CG (1999), Proc Biol Sci vol. 266, (1432) 19952002, 10.1098/rspb.1999.0877 Adapted text taken from: Skin morphology and its role in thermoregulation in mole-rats, Heterocephalus glaber and Cryptomys hottentotus, Daly TJ and Buffenstein R (1998) J Anat. 193(Pt 4): 495502; doi: 10.1046/j.1469-7580.1998.19340495, retrieved 11 November 2011 from PMCID: PMC1467874 Copyright 1998
Comment [SVR103]: the set of chromosomes and the genes they carry

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