Tuesday, November 12, 2019
Cellular Basis of Life
What is Life? This perennial question the answer to which has somehow eluded the most brilliant minds. For while scientists have identified many years ago the right mix of the atoms and molecules that constitute cellular material, they have not succeeded in ââ¬Ëswitching it onââ¬â¢ to make it alive, or ââ¬Ëbreathing lifeââ¬â¢ into it (Rabago et. al,2006) In this module you will: a. Explain the concepts of the cell theory b. Identify the parts of a cell c. Describe the function of each cell part d. Differentiate prokaryotic from eukaryotic cells e. Compare plant and animal cells A. The Cell Theory ââ¬â tructurally made up of 1. What are living things made of? cells. ââ¬â 2. What can cells do? 3. Where do cells come from? All living things are The cell is the fundamental unit of life. ââ¬â Cells come from the division of pre-existing cells. B. Cell Structure and Composition CELL MEMBRANE -Serves as the outer boundary of the cell. It is a selective permeable memb rane which permits the entrance of substances throughout the cell. CYTOPLASM -Serves as the reservoir of the organelles as it contain all the lifesustaining components. It is a jellylike structure. NUCLEUS -Usually located at the center and nown as the control center of the cell. It regulates and coordinates all the activities of the cell. C. Organelles in the Cytoplasm ORGANELLES STRUCTURE Membrane Components Module 8 A. 1. smooth endoplasmic reticulum ââ¬â usually the site for fat metabolism; forms vesicles for transporting large molecules to other cell parts 2. mitochondria ââ¬â sites of cellular respiration 3. Golgi apparatus ââ¬â involved in modifying, sorting and packaging macromolecules for secretion or for delivery to other organelles 4. nuclear membrane ââ¬â a double membrane which separates the nucleoplasm from the cytoplasm . nucleolus ââ¬â the site where subunits of ribosomes are formed 6. nuclear pore ââ¬â serves as pathway for the exchange of materials between the nucleus and the cytoplasm 7. rough endoplasmic reticulum ââ¬â studded on its outer surface with ribosomes for the synthesis of protein FUNCTION D. Variations in Cell Structure and Function d. 1 Prokaryotic Cell vs. Eukaryotic Cell A typical Prokaryotic Cell A typical Eukaryotic Cell Prokaryotic Cells Eukaryotic Cells Pro = ââ¬Å"beforeâ⬠, karyon = ââ¬Å"nucleusâ⬠Eu = ââ¬Å"trueâ⬠, karyon = ââ¬Å"nucleusâ⬠Prokaryotes are evolutionarily ancient. They were here first and for illions of years were the only form of life. And even with the evolution of more complex eukaryotic cells, prokaryotes are supremely successful. All bacteria and bacterialike Archaea are prokaryotic organisms. Eukaryotic cells are more complex, evolving from a prokaryote-like predecessor. Most of the living things that we are typically familiar with are composed of eukaryotic cells; animals, plants, fungi and protists. Eukaryotic organisms can either be single-celled or multi-celled. PROKAYOTIC EUKARYOTIC Nucleus: Present Number of chromosomes: More than one Cell Type: True Membrane bound Nucleus:Example: Multicellular Absent Oneâ â¬âbut not true chromosome: Plasmids Unicellular Present Absent Animals and Plants Telomeres: Present (Linear DNA) Genetic Recombination: Mitosis and fusion of gametes Lysosomes and peroxisomes: Microtubules: Endoplasmic reticulum: Mitochondria: Cytoskeleton: DNA wrapping on proteins. : Ribosomes: Vesicles: Golgi apparatus: Mitosis: Present Present Present Present Present Yes larger Present Present Yes Chloroplasts: Present (in plants) Bacteria and Archaea Circular DNA doesn't need telemeres Partial, undirectional transfers DNA Absent Absent or rare Absent AbsentMay be absent No smaller Present Absent Noââ¬âbut has binary fission Absent; chlorophyll scattered in the cytoplasm Flagella: Microscopic in size; membrane bound; usually arranged as nine doublets surrounding two singlets Submicroscopic in size, composed of only one fiber Selective not present Yes Usually no Permeability of Nuclear Membrane: Plasma membrane with steriod: Cell wall: Vacuoles: Cell size: Only in plant c ells (chemically simpler) Present 10-100um Usually chemically complexed Present 1-10um d. 2 Plant Cell vs. Animal Cell Plant Cell Animal Cell Characteristics Plant Cell Cell SizeLarge Cell Shape Rectangular Vacuoles A single centrally located vacuole. It takes up almost 90% of the cell volume. The vacuole stores water and maintains turgidity of the cell. Cell Wall Chloroplasts Cell Division A rigid cell wall (made of cellulose) is present around a plant cell that helps it maintain its shape. Present. Chlorophyll is the pigment that traps sun's energy which is utilized by plants to make food through the process of photosynthesis. This pigment is present in the chloroplasts. Cell division takes place by the formation of cell plate in the center of the dividing cell.This becomes the cell wall between the two daughter cells. Centrioles Present only in lower forms. Plants instead have microtubule organizing centers (MTOC) that produce the microtubules. Centrosome Absent. Instead two smal l clear areas called polar caps are present. Absent Lysosomes Golgi Bodies In place of golgi bodies, its sub units known as dictyosomes are present. Animal Cell Smaller than plant cells Circular If any, there are a number of small vacuoles spread throughout the cytoplasm that store water, ions and waste materials. Cell wall is absent. This allows animal cells to adopt different hapes. Absent. As animals lack this pigment, they cannot make their own food. Animal cells divide with the formation of a cleavage furrow. This is formed as the chromosomes move to the ends of the microtubule spindle formed by the centrioles. Present. Centrioles help in division of animal cells by creating microtubule spindles that pull the chromosomes to opposite ends for cell division to occur. Present Present. Lysosomes are vesicles that contain enzymes that destroy dead cell organelles and other cells debis. Complex golgi bodies are present close to the nucleus. E. Articles about CellBBC NEWS-Last Updated : Tuesday, 20 November 2007, 16:42 GMT Stem cells are thought to hold huge potential for treating a wide range of disease and disability. Scientists around the world are working on techniques to Refine stem cell therapy. The latest technique, nuclear reprogramming, promises to solve some of the trickiest practical and ethical issues. What are stem cells? Most adult cells in the body have a particular purpose which cannot be changed. For instance, a liver cell is developed to perform specific functions, and cannot be transformed to suddenly take on the role of a heart cell.Stem cells are different. They are still at an early stage of development, and retain the potential to turn into many different types of cell. Why are they so useful? When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function. Scientists believe it should be possible to harness this ability to turn stem cells into a super â â¬Å"repair kitâ⬠for the body. Theoretically, it should be possible to use stem cells to generate healthy tissue to replace that either damaged by trauma, or compromised by disease.Among the conditions which scientists believe may eventually be treated by stem cell therapy are Parkinson's disease, Alzheimer's disease, heart disease, stroke, arthritis, diabetes, burns and spinal cord damage. Stem cells may also provide a useful way to test the effects of experimental drugs. It is also hoped that studying stem cells will provide vital clues about how the tissues of the body develop, and how disease takes hold. Are there different types of stem cell? Yes. Scientists believe the most useful stem cells come from the tissue of embryos.This is because they are pluripotent ââ¬â they have the ability to become virtually any type of cell within the body. Stem cells are also found within adult organs. They have not taken on a fina l role, and have the potential to become any of the m ajor specialized cell types within that organ. Their role is to maintain the organ in a healthy state by repairing any damage it suffers. It is thought their potential to become other types of cell is mo re limited than that of embryonic stem cells. But there is evidence that they are still relatively ââ¬Å"plasticâ⬠. Can they be easily grown in the lab?Large numbers of embryonic stem cells can be relatively easily grown in culture. However, adult stem cells are rare in mature tissues and science is still working on ways to grow them in the lab in sufficient numbers. This is an important distinction, as large numbers of cells are needed for stem cell replacement therapies. Is the use of stem cells controversial? Very. Campaigners are vehemently opposed to the use of embryonic stem cells. These cells are typically taken from lab-created embryos that are just four or five days old, and are little more than a microscopic ball of cells.However, opponents argue that all embryos, wh ether created in the lab or not, have the potential to go on to become a fully-fledged human, and as such it is morally wrong to experiment on them. They strongly advocate the use of stem cells from adult tissue. What is nuclear reprogramming? A new technique, in which cells isolated from skin tissue called fibroblasts are modified by inserting gene-controlling proteins. This chemical cocktail causes the cells to be ââ¬Å"reprogrammedâ⬠to take on the plastic quality of embryonic stem cells. Why is the nuclear reprogramming an advance?There are two big potential benefits. The current methods derive stem cells from from existing lab lines, but these cells are foreign to the body, and run the risk of rejection if used to repair or replace damaged or diseased tissue. Nuclear reprogramming can potentially produce a supply of stem cells derived from a patient's own tissue ââ¬â avoiding the issue of rejection of the cells. Secondly, the technique does not require the creation of , or destruction of an embr yo, and so is not ethically contentious. Are there safety concerns? Yes.Some researchers fear that it is possible that stem cell therapy could unwittingly pass viruses and other disease causing agents to people who receive cell transplants. Some research has also raised the possibility that stem cells may turn cancerous. Work also still needs to be done to refine the new technique. Similar results were achieved by two teams using a different combination of gene-controlling proteins. In both cases the success rate in producing new stem cells was also low. Last Updated: Monday, 8 January 2007, 08:58 GMT ââ¬ËNew stem cell source' discoveredUS scientists say they have discovered a new source of stem cells that could one day repair damaged human organs. Researchers successfully extracted the cells from the fluid that fills the womb in pregnancy and then grew them in lab experiments. The types of stem cell with potentially the most use have so far been deriv ed from specially grown human embryos. But this has created ethical concerns because the embryos are destroyed in the process. Opponents say this is tantamount to cannibalism. Supporters say stem cells offer real hope in treating illnesses like diabetes, Parkinson's and Alzheimer's.Implanted in mice Writing in Nature Biotechnology, the scientists said it should be possible to harness the cells' ability to grow into different tissue to treat disease. ââ¬Å" It shouldn't be seen as a race between embryonic stem cells and other sources â⬠Prof Colin McGuckin Newcastle University However, UK experts had doubts about the feasibility of the technique. They said gathering amniotic fluid from large numbers of women might be difficult. Amniotic fluid contains a large number of cells, many of which come from the developing foetus.The team from Wake Forest University School of Medicine, in North Carolina, extracted these from fluid samples taken as part of unrelated diagnostic tests duri ng pregnancy, then encouraged them to grow in the laboratory. They found that they had the potential to turn into a wide variety of different cells ââ¬â the hallmark of potentially useful stem cells. They then transplanted them into mice, and carried out further tests to look at how they performed in a living creature. Again, the results were encouraging, with the stem cells spreading and starting to produce key body chemicals in both brain and liver.Bone stem cells introduced onto an artificial ââ¬Ëscaffold' then implanted into mice also appeared to behave in a similar way to normal bone cells, forming bone even months later. Great interest The conclusion of the researchers was that the amniotic cells were ââ¬Ëpluripotent' ââ¬â capable of becoming many different cell types, and that they held the potential for treatment ââ¬â particularly on the child from whose mother they were taken, for whom they are an exact tissue match. Dr Paolo De Coppi, now of Great Ormond Street Hospital, who worked on the study, said the amniotic stem cells were similar to, but not identical to, embryonic stem cells.He said: ââ¬Å"Our research suggests that for some clinical applications they may work better than embryonic stem cells. ââ¬Å"For example, embryonic stem cells injected into muscle can form teratomas ââ¬â amniotic stem cells do not do this. ââ¬Å"However, the range of applications for these stem cells may be more narrow than for embryonic stem cells. â⬠Dr De Coppi it might be possible to take amniotic stem cells from a child diagnosed before birth with a problem, and use them to grow new tissue in the laboratory, which would be ready to use to treat the child when it was born.In theory, it might also be possible to genetically modify a foetus' own stem cells and inject them back into the amnioitc fluid to correct gene disorders. Possible limitations Professor Colin McGuckin, from Newcastle University, is researching the use of similar cells taken from the umbilical cord at birth. He welcomed the report, saying that it was ââ¬Ëthorough' and demonstrated the potential of amniotic stem cells. ââ¬Å"The best thing is to have a variety of stem cell sources to provide the best stem cell for patients. Unless researchers do work to demonstrate there are alternatives to embryonic stem cells, the wider public won't understand that. It shouldn't be seen as a race between embryonic stem cells and other sources. â⬠However, he said that harvesting amniotic fluid presented particular difficulties in many cases. ââ¬Å"If it is a natural birth, the waters break and they are all over the floor, and you've lost them. In this country, the majority of women give birth naturally, which means that fluid could not be collected. ââ¬Å"You could conceivably gather amniotic fluid during a caesarean section, but that process could interfere with the experience of giving birth. â⬠Wednesday, 15 November 2006, 18:00 GMT Stem cells ââ¬Ëtreat muscle disease'A stem cell breakthrough could lead to a treatment For muscular dystrophy (MD), research has revealed. An Italian-French team found transplanting stem cells into dogs with a version of the disease markedly improved their symptoms. Writing in the journal Nature, the team said the work paved the way for future trials in humans. Scientists said it was a major step forward and bolstered the idea that stem cells could be used to treat MD. ââ¬Å" This is the first piece of research that has convinced me that stem cell therapy could play a role in treatment for Duchenne muscular dystrophy â⬠Professor Dominic WellsMuscular dystrophy is a group of genetic disorders that cause the muscles in the body to gradually weaken over time and mobility to be lost. It shortens life span and there is currently no cure. The researchers, led by a team at San Raffaele Scientific Institute, in Milan, Italy, looked at the most common form of the disease, Duchenne muscular d ystrophy. This condition, which usually only affects boys, appears in about one in every 3,500 male births and is caused by mutations in a particular gene that lead to a lack of dystrophin, a protein involved in maintaining the integrity of muscle.The team had previously seen promising results when they injected stem cells into mice with a version of this disease, but turned to dogs for their next trial because they replicate the musclewasting disease more accurately. Mobility returned The researchers used a form of stem cells, gathered from blood vessels, called mesoangioblasts, which are ââ¬Å"programmedâ⬠to turn into muscle cells. They isolated the stem cells from both healthy dogs and also from MD dogs, with the latter's stem cells then being modified to ââ¬Å"correctâ⬠the mutated gene. The scientists proceeded to inject these different types of stem cells into dogs with MD.They found that transferring the stem cells five times at monthly intervals produced the bes t results. Overall, injections of stem cells taken from healthy dogs showed the most improvement. Four out of the six dogs who received these stem cells saw the return of dystrophin and regained muscle strength. One dog that was injected at an early-stage of the disease retained the ability to walk, and two dogs injected at a late-stage of the disease had their mobility returned. Of the remaining two, one died early and the other, the scientists believe, did not receive enough cells.The experiment to inject MD dogs with their own ââ¬Å"correctedâ⬠stem cells proved less successful, although the dytrophin protein returned. This approach was investigated because, should stem cell treatment move into humans, it would mean patients could be injected with their own cells, minimising the chances of rejection and avoiding the need to take immunosuppressant drugs. The researchers wrote: ââ¬Å"The work reported here sets the logical premise for the start of clinical experimentation th at may lead to an efficacious therapy for Duchenne muscular dystrophy. ââ¬ËExcellent work' Dr Marita Pohlschmidt, director of research at the Muscular Dystrophy Campaign, UK, said: ââ¬Å"We feel encouraged by the work because the results provide initial evidence that we might be one step closer to a stem cell treatment for Duchenne muscular dystrophy. â⬠Dr Stephen Minger, a stem cell researcher at Kings College London, said: ââ¬Å"This is an excellent piece of work demonstrating significant functional improvement in a naturally occurring disease in dogs that is very similar to that in humans. Although it will likely to be some time before this work can move to humans, it is nevertheless an important study in developing therapies for muscular dystrophies. â⬠Professor Dominic Wells, of the gene targeting group at Imperial College, London, said: ââ¬Å"This is yet another example of the vital contribution animal research makes to the development of treatments for human disease. ââ¬Å"This is the first piece of research that has convinced me that stem cell therapy could play a role in treatment for Duchenne muscular dystrophy. ââ¬Å"Kay Davies of the MRC Functional Genetics Unit, University of Oxford, said: ââ¬Å"The use of stem cells to treat human disease holds great promise, but the actual delivery of such therapy is thought to be many years away. â⬠The data, she said, changed this view. However, she added that the researchers needed to find out why not all dogs responded positively. Wednesday, 8 November 2006, 16:48 GMT Cell transplants ââ¬Ërestore sight' Cell transplants have successfully restored vision to mice which had lost their sight, leading to hopes people could enefit in the same way. UK scientists treated animals which had eye damage similar to that seen in many human eye diseases. They were able to help them see again by transplanting immature retinal stem cells into their eyes. UK experts welcomed the study, published i n the magazine Nature, saying it was ââ¬Å"stunningâ⬠research. ââ¬Å" This is a stunning piece of research that may in the distant future may lead to transplants in humans to relieve blindness â⬠Professor Andrew Dick University of BristolIf the results can be translated into a treatment for human eye disease, it could help the millions of people with conditions ranging from age-related macular degeneration to diabetes. Once the cone and rod photoreceptors in a retina are lost, they cannot be replaced. While treatments are being developed which might prevent or delay the loss of these cells, scientists are also seeking to help those already affected. It is thought the retina is one of the best places to try out cell transplant therapy because photoreceptor loss initially leaves the rest of the wiring to the brain intact.But previous attempts to transplant stem cells, which can turn into any kind of cell in the body, in the hope that they will become photoreceptors have failed because the cells were not developed enough. Harvest In this study, funded by the Medical Research Council, scientists from the University College London Institutes of Ophthalmology and Child Health and Moorfields Eye Hospital transplanted cells which were more advanced, and already programmed to develop into photoreceptors. ? 1 ââ¬â Early stage retinal cells are taken from a newborn mouse ? 2 ââ¬â They are transplanted into the retina of a mouse which has lost its sight ? ââ¬â The cells implant and connect with existing cells in the eye, restoring some sight to the mouse. The team took cells from three to five-day-old mice, a stage when the retina is about to be formed. The cells were then transplanted into animals which had been genetically designed to have conditions which meant they would gradually lose their sight ââ¬â either mimicking the human disease retinitis pigmentosa or age-related macular degeneration. The transplants were successful; the photorec eptors implanted and made electrical connections to the animals' existing retinal nerve cells ââ¬â key to allowing them to see again.Tests showed that the mice's pupils responded to light and that there was activity in the optical nerve, showing signals were being sent to the brain. Dr Jane Sowden, one of the study's leaders, said: ââ¬Å"Remarkably, we found that the mature retina, previously believed to have no capacity for repair, is in fact able to support the development of n ew functional photoreceptors. â⬠ââ¬ËNot false hope' To get human retinal cells at the same stage of development, however, would involve taking stem cells from a foetus during the second trimester of pregnancy.But Dr Robert MacLaren, a specialist at Moorfields Eye Hospital who worked on the research, said they did not want to go down that route. He said the aim now would be to look at adult stem cells to see if they could be genetically altered to behave like the mouse retinal cells. There are some cells on the margin of adult retinas that have been identified as having stem cell -like properties, which the team says could be suitable. Dr MacLaren stressed it would be some time before patients could benefit from such a treatment, but he said that at least it was now a possibility. Every day, I sit in my clinic and have to tell patients that there's nothing I can do. ââ¬Å"I don't want to give patients false hope. But at least now, if I see a young patient, I can say that there might be something within your lifetime. â⬠Dr Stephen Minger, a stem cell expert at King's College London, said: ââ¬Å"I think this is important, superb research ââ¬â it clearly shows that the host environment is important in directing the integration of transplanted cells. â⬠But Andrew Dick, professor of ophthalmology at the University of Bristol, added: ââ¬Å"As with any basic research we have to be careful not to overhype.Remove the Jello from the plastic cup onto the paper pla te. We had some problem with this. The students may need to run the knife around the very outside edge of the Jello to loosen it. There are some suggestions that you might spray the cup with Pam or some other non -stick material. We did not get a chance to try this yet. Running warm water over the cup may also loosen the Jello. 3. Cut the Jello/Knox in half and remove the top half. Turn over the top and set it on the plate beside the bottom half 4. Use the spoon to dig out a hole in the bottom half of the Jello/Knox cytoplasm . Just pushing the food pieces into the Jello causes it to crack and come apart, making for a very messy cell.Place the gumball in this hole to represent the nucleus of the cell. 5. Using the spoon to make spaces and your diagram as a guide, place the other cell parts into the cell. Parts can be put into both the top and bottom half of the Jello/Knox cell 6. Take the top part of the cell and carefully place it on the top. If the cell feels soft, you can put the parts back into the plastic cup, then turn it over onto the paper plate. Then carefully remove the plastic cup. 7. After reviewing the parts one final time, those students who wish to can feast on their cell. Please use clean spoons in case the spoon you were working with fell on the floor or the table. It's Alive, Alive.Background: You will be in groups of three, each with your own job. The jobs to choose from are Contractor, Architect, and Surveyor. Your job, as a group, is to build the most realistic life-like plant cell the world has ever seen. Problem: What does a 3-dimensional cell look like? What are the various parts of plant cells? Materials: Play-doe, food coloring or tempera paints (red, purple, green, blue, white), 1 pair of gloves, yarn or undercooked spaghetti, pepper, plastic-bubble packing, aluminum foil, plastic wrap, pencil shavings, scissors, 1 large knife, glue. Procedure: 1.Before we start be aware that on the final day you must present your cell to the class. 2. After you have decided upon your jobs, the Contractor and Architect will collaborate to design the plant cell. The design should be drawn up on a piece of paper that explains what materials will be used for each organelle. It should be colored the same color it will appear when it is built. Take your time and make a good drawing. This should be completed early on day two. Throughout this entire process the Surveyor should be writing down the order in which each organelle was designed and the order in which it will be built. Along with this the Surveyor must make a copy of the design that the group can use when building it.The Surveyor's job is to basically take notes all the way through, so if the final product doesn't come out as planned the Surveyor can look back at their notes and answer why. 3. After you have finished your design, hand it in and your teacher will approve it. If it is approved, you can start to build your cell. 4. Building should be the role of the contractor. Architect's watch the bui lders to make sure they are doing it exactly as planned. Surveyors should take notes on how it is built and also can assist the Architects to make sure it is being built as planned. It's Just a Phase They're Going Through! Problem: What phases do cells undergo during mitosis? What happens at each phase?Materials: Unlined paper (1 sheet), colored pencils, pencil, crayons, light microscope, slides, cover slips, onion (fresh), toothpicks, knife (used by teacher only), iodine stain. Procedure: Procedure Part A: Slide Preparation Onion Skin a. First take a piece of onion skin off the onion. b. Put it flat on a slide. c. Bring the slide to the leader for a drop of iodine stain. Data Sheet d. Carefully put on a cover slip remembering to angle it. e. Examine the cell under low then medium power. 1. Front f. Adjust your microscope to a higher power. 2. Procedure Part B: Data Preparation 3. Back 1. You will take your paper fold and it in half, label each ox created (front + back) numbers 1 ââ¬â 4 as shown on the right. 4. 2. Create a large box within numbered box, as shown. 3. Within the large area you will draw the stages of mitosis, make them colorful. 4. Within the smaller box you will write the name of each stage shown, and give a full description of what you see happening.Cells Vocabulary Quiz Directions: Match the vocabulary words on the left with the definitions on the right. 1. tissue the central, essential, or highly concentrated part around which other parts are grouped. 2. vacuole a musical instrument consisting of a keyboard attached to a device that forces air through a number of pipes to produce a wide range of sounds; pipe organ. 3. chromosome storage areas of the cell known for storing mostly water and/or food. 4. chlorophyll (chlorophyl) the ground protoplasm of cells that is outside the nucleus. 5. cell membrane Shaped like a bean, this cell organelle helps take food and manuf acture energy from it. 6. chloroplastA struct ure inside the nucleus where RNA is transcribed. 7. cell wall the mass of like cells in an animal or plant body, esp. as they form a specific organ: 8. nucleolus Thin, intertwined pieces of DNA found in the cell's nucleus. 9. organ the green (in color) pigment found in chloroplasts where photosynthesis takes place. 10. cytoplasm Mostly made of cellulose, this is the tough and rigid outer layer of plant cells. 11. nucleus an egg shaped body that appears green from all the chlorophyll they contain. This organelle is where photosynthesis takes place. 12. mitochondrion The enclosure of the cell that provides the body for all the organelles.Cells Word Chop Worksheet Directions: The table below contains words that have been chopped in half. Find the pieces that fit together and write them in the answer area below. osome vac sues chrom tis cell chlor org leus embrane ophyll eolus ans ondria cell m oplast nucl nuc chlor plasm cyto mitoch uole wall.
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