You are on page 1of 93

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

BIOL102Alaie Notes By Barukh Rohde


February 1 Notes: Plasmodesmata are holes in the semirigid cell walls of plants where ions and other substances can pass between cells. The tonoplast is the semipermeable membrane of the central vacuole. Water normally moves across a membrane according to its concentration gradient. Animal cells have a normal state in an isotonic solution, with some ions in the extracellular fluid. They shrivel in hypertonic solutions, and burst in hypotonic (pure water, few ions) solutions. Plant cells are normally in a turgid state in a hypotonic solution, where the cell presses upon the cell wall, where the wall pushes back on the cell to prevent any more water from entering. The plant cell is flaccid and wilts in isotonic solutions, and the membrane pulls away (plasmolyzes) from the wall in a hypertonic solution. The cell wall adds a pressure component to the direction of water movement. It resists water potential, the tendency of water to move from one location to the next. Water potential has a pressure component and a solute component. Differences in water potential determine the direction that water moves across a membrane. Water always moves from a location with a higher water potential to a location with a lower water potential. If water and an ion solution are placed on opposite sides of a U-tube, with a water- but not ion-permeable membrane, water will cross to the ion side until the weight of the ion water stops water from flowing in any more and the system is in equilibrium. If a piston is placed on the ion side, the concentration gradient will support the piston equal to the wave potential pressure. Unless the pressure component and solute component of water potential are equal, there will be net movement to the side of lower water potential. Plants lose water as an inevitable side effect of exchanging gases with the environment during photosynthesis. A plant must open its stomata, openings in leaves guarded by guard cells, to gain carbon dioxide from the environment. However, water is lost to the environment through these pores. Plants must ensure that they dont dehydrate as they take in carbon dioxide, so the stomata are consistently opening and closing in response to external conditions and the plants level of hydration. Water loss from the aerial parts of trees is known as transpiration, through evaporative water loss. A tree must move water from its roots to its shoots and leaves as all parts of the tree need water. Water is responsible for maintaining turgid pressure, moving nutrients, participating in photosythess, moving sugars from source to sink and cooling the leaves due to evaporative water loss through the stomata. Transpiration also cools the plant leaves, which is helpful to the plant. Guard cells are not uniformly think, and cellulose microfibrils are oriented in a direction that causes cells to buckle outward when theyare turgid. When the cells are turgid, the stomata are open. When the cells are flaccid, the stomata are closed. When a stoma (singular of stomata) are closed, protons are pumped out, potassium and chloride ions are pumped in, with water following them. This water makes the stoma turgid and open, which results in the water, chloride, and potassium leaving, and the stoma will close again. Diffusion of water from the roots to the tops of tall trees could take decades long distance movement of water is done through bulk flow, the movement of a fluid driven by pressure difference. There is a water potential gradient from roots to shoots: the soil water potential is high (unless extremely dry), the root potential is medium-high, the leaf potential depends on the transpiration rate (low when stomata are open), and the atmospheric

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 1

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

potential changes with humidity, but is usually very low. This pull is transmitted all the way along the xylem of the plant, requiring no energy on the part of the plant. Questions: In receptor-mediated endocytosis, receptors on the outside of the plasma membrane bind to food before the cell ingests it. Why dont plants use receptor molecules for carbon dioxide on the outside of their leaves instead of wasting water by having open stomata? Alaies slide says water is responsible for maintaining turgor pressure is that just another word for keeping the plant cells turgid and upright? If water cohesion (with adhesion) moves the water up to the other cells of the plant, why doesnt cohesion lead to the streams of water following water involved in transpiration right out of the cell? How can the plant as a whole control the opening and closing of its guard cells if they continuously open and close with protons, potassium, chloride, and small amounts of water flow? February 3 Notes: Root cells have root hairs with large surface areas in order to exchange gases, ions, water and minerals with the soil. Soil particles are negatively charged, so cations are attracted to them. When the soil is dry, the root hair must change the water potential so that its water potential is lower than that of the soil. So the root hair discharges protons, which displace cations on the soil particles. The osmotically-active cations are then absorbed by the root hair, lowering the solute component of the water potential. Water then follows the cations. The living portion of a plant cell is known as the symplast once. Once water or an ion crosses the plasma membrane, it is inside the symplast. The nonliving portion made up of the cell walls and extracellular space is known as the apoplast. Water can move transmembrane across the apoplasts and symplasts, symplastic along only the symplasts, or apoplastic along only the apoplasts. But anything going along the apoplastic route must eventually cross into the symplast because of the Casparian Strips, which form a barrier between the cortex and stele. This barrier prevents harmful ions such as lead, nickel, zinc, and excess sodium from entering the xylem. Eventually, water must get to the xylem, where it will be transported to the rest of the plant. Water-conducting cells of the xylem are dead, without any organelles or cytoplasm that would hinder the flow of water. Only the walls stay, becoming either vessel elements or tracheids. Vessel elements are wider, with partially perforated end walls. Tracheids are longer but thinner, with pits and tapered ends. Xylem cell walls consist of hydrophilic cellulose that adhere to water molecules, and the pits/perforations allow water to flow between xylem cells. Cohesion between water molecules and adhesion to xylem cell walls, along with water potential, moves water up the plant. Root pressure is not a positive push from below that pushes the water up the plant. Gravity overcomes that. But when water is transpired, the column of water moves upward, too. As water evaporates from liquid into gas in the meniscus of the leaf, water molecules beneath and above are pulled into its place. Transpirational pull happens when the evaporative water loss from the spaces in the leaf out into the atmosphere places a pull on the liquid water that is at the air-liquid interface in the meniscus of the leaf. The loss of a water molecule from this interface causes another water molecule to attempt to move into its place, and water molecules beneath it will cohere into its place, transmitting a pull down the column of water. Movement in the xylem is based on bulk flow, unidirectional from the roots to the shoots. The pressure in the xylem is a negative pressure. Xylem cells are dead. Phloem cells are living at functional maturity, although they have cleared out many of the

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 2

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

organelles to facilitate sugar movement. Most of the remaining organelles are pushed to the side. Phloem sieve cells also have companion cells with organelles that provide for the needs of the sieve tube member, in addition to loading sucrose into it. The flow of phloem sap is also bulk flow, but from a positive pressure. It is multidirectional, from source to sink. Questions: Arent cells negatively charged, too? Why dont cations attract to it? Why must they release protons to displace cations from the soil particles? February 8 Notes: Sucrose is transported into the companion/sieve tube member against its concentration gradient by proton/sucrose cotransporters (protons down their gradient) in the plasma membranes of companion cells and sieve tube members. Proton pumps then pump the protons back across the membrane, making sugar loading a form of (secondary) active transport. Sugars can be translocated rapidly, 50-100 cm/h through the plant. Sugar is moved from source (photosynthesis and starch breakdown) to sink (consumer/storer of sugar). Once sucrose is loaded into the sieve tube members of the phloem, the water potential of these cells is lowered beneath that of the water potential of the xylem. Thus, water moves from the xylem to the phloem and builds up pressure. The phloem sap then moves from higher pressure region to the lower pressure region. The lower pressure region of phloem exists because sugar is unloaded at the sink. Sugar leaving the sieve tube member increases the water potential in the cell and allows water to leave and reenter the xylem. So water potential drives the sugar movement in the phloem, too. Sugar unloading can be passive or active. It is passive if the sugar in the sink is used immediately for the various functions needed in building the leaf, keeping the concentration gradient from high concentration in the phloem to low concentration in the leaf. But if the sucrose is stored as sucrose, just building up in the sugar sink, as in the example of a fruit or a root cell, then sucrose would be moving through active transport against its gradient. The plant would need to expend energy to transport the sucrose into the sink. Xylem sap moves through dead vessel elements and tracheids, due to transpiration from leaves and a negative pressure potential. Phloem sap moves through living sieve tube members, due to active transport of sucrose into the phloem at the sugar source, with a positive pressure potential. Now we start Chapter 16: If heat-killed S (with protein capsule) bacterial cells are mixed with living R (without capsule) harmless cells, the R cells will pick up the harmful genes of the S strain, and display a phenotype identical to that of living S cells (their reproduced descendants acquire DNA from the dead S cells, and develop a capsule). Avery, McCarty, and Macleod tested the macromolecules released by the heat-killed S strain to narrow down which material was the genetic material, responsible for the transformation of the nonpathogenic strain into the pathogenic strain. They found that only DNA was capable of transforming the bacteria, therefore it must be the transforming factor. Hershey and Chase found that when bacteriophages infect bacteria, the phage DNA is ejected into the bacteria. They radioactively tagged phosphorus and sulfur atoms and put them in phages, finding that the phosphoruscontaining DNA was ejected into the bacterial cell but sulfur-containing protein was not.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 3

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

February 10 Notes: The Hershey-Chase experiment involved radioactively tagging protein and DNA in bacteriophages, allowing the phages to attach to the bacteria and checking afterwards whether radioactivity would be emitted by whichever genetic material that was put in the

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 4

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

bacteria. Only radioactive DNA was found in the bacteria, not radioactive protein, so therefore DNA is the genetic material. This experiment led to many more experiments on DNA, allowing scientists to discover the makeup of it. A typical human chromosome has approximately 150 million nucleotide pairs. DNA polymerase moves at a speed adding approximately 50 nucleotides per second. (It would take over 800 hours for one to complete.) So there are multiple DNA polymerases. DNA replication begins at specific A-T rich sites along the chromosome called origins of replication, or oris, which are located every 30,000-250,000 base pairs. Replication occurs during the mitotic phase. As we learned in BIOL100, there are checkpoints in the cell cycle to ensure that the cell is behaving normally. When DNA replicates, the parent DNA molecule is separated into its two strands. Each parental strand serves as a template that determines the order of nucleotides along a new complementary strand. The complementary nucleotides are joined together to form the sugar-phosphate backbone of the complementary strand, the complementary and original strands fuse, and there are two identical double-stranded daughter molecules of DNA. This is called semi-conservative replication. To determine the method of DNA replication, Moselson and Stohl used different isotopes of nitrogen. They made the original DNA molecule with heavy nitrogen, and attempted to see what the percentage of heavy nitrogen would be after duplicating a few times with light nitrogen available in the area. Conservative replication would mean that the two parental strands would find one another after serving as templates. Semi-conservative replication would be where each parental strand stayed paired with the new strand it coded for. Dispersive replication would be where each DNA duplex would contain portions of its double helix that were fully parental, and portions that were fully new. If bacteria was grown exclusively in media containing heavy nitrogen, and DNA was put with it in a test tube, and the bacteria was brought to media containing light nitrogen and allow only one round of replication to occur before isolating the DNA, then the conservative method could either be confirmed or ruled out based on the state of the nitrogen in one helix (if conservative, one helix would be entirely heavy DNA and one entirely new DNA). They found that when filtered there were not two types of DNA with different types of nitrogen, both helices had both types in a single hybrid band. In a second round of replication, there were hybrid bands and light nitrogen-only bands, proving the semiconservative theory. DNA is in antiparallel form, with a 5-3 strand and an opposite 3-5 strand. DNA polymerase only synthesizes new strands in the 5-3 direction. It adds nitrogenous bases to the free hydroxyl on the 3 end of a growing strand. It reads the DNA in the 3-5 direction.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 5

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

February 15 Notes: DNA polymerase reads DNA in the 3-5 direction, and therefore must synthesize new DNA strands in the 5-3 direction. It adds new nucleotides to the free 3 hydroxyl of the new, growing strand. At the end, a new duplex is created from one parental strand that serves as a template and the second newly-created strand. A DNA strand is highly negatively charged due to the many phosphate groups on the sugar-phosphate backbone. The energy for the addition of new nucleotides comes from the original 3 phosphate groups on the nucleotide. ATP loses two phosphate groups, and adenosine with a single phosphate group (AMP) uses the released energy to attach to the growing strand. The released pyrophosphate (2 attached phosphate groups) can then be cleaved again, releasing more energy and leaving two inorganic phosphates. DNA polymerase cannot synthesize a new strand from scratch. DNA polymerase adds to the free 3 end of a short RNA strand. New DNA strands must be started (primed) with a short stretch of nucleotides. Humans use RNA primers which are each 5-10 nucleotides long. This RNA primer will be removed and replaced with DNA nucleotides before strands are finished. DNA primase makes RNA primers to start replication. This RNA stretch will be deleted and replaced with DNA before the duplex is finished. Primase also synthesizes in the 5-3 direction, in several locations on the DNA, preparing the area for DNA to continue the strand from the 3 end with DNA nucleotides. The leading strand only needs to be primed once, with the DNA polymerase continuously following the helicase unwinding the original helix. But the lagging strand is being opened on the 3 side, and DNA is made in the 3-5 direction. So many primers are put down as the helix is unwound, and Okazaki fragments, 200 nucleotides long along the lagging strand, are formed. Eventually, DNA will be put in the place of the RNA primers, and ligase connects the fragments together. The RNA primers will be hemmed and

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 6

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

DNA will be synthesized in their place using the 3 end and the DNA strand that is adjacent to it. The most recently synthesized DNA is the part closest to the replication fork. Topoisomerase nicks DNA to relieve tension from unwinding (this nick will later be sealed). Helicase opens the helix, is responsible for unwinding the 2 parental strands from one another. Cooperative singlestrand binding protein straightens the open region of the chain to prevent secondary intermolecular bonding from occurring. DNA primase makes the RNA primer that starts the new DNA polymerase. DNA polymerase adds to the RNA primer, making either a leading strand or an Okazaki fragment. And finally, DNA ligase seals the sugar-phosphate backbones of the Okazaki fragments together. The DNA helicase and primase make up a primosome which unwinds and primes the helicase for the Okazaki fragments. The sliding clamp holds the DNA polymerase in place on the strand. The clamp loader puts a clamp on a strand. Now see if you can name the strands and proteins in the picture below:

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 7

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

February 17 Notes: The leading strand is the one with its DNA polymerase in the replication fork, created in the 5-3 direction. The lagging strand has Okazaki fragments, in the 3-5 direction of the strand but created in the 5-3 direction only. Senescent cells no longer divide, exiting permanently from the cell cycle. Each chromatid has repeated DNA sequences called telomeres at their ends. These telomeres will shorten in any somatic cell as cell division proceeds, so long as telomerase (which maintains the telomeres) isnt active. This shortening is due to the fact that DNA polymerase cannot attach at the very beginning of a strand; only at a point with nucleotides at both sides of the attachment point because the primer must attach ahead of replication. The telomeric sequence is 6 nucleotides long, repeated up to 1000 times. The absolute 3 ends of the parental strands are normally copied by the telomerase enzyme, which adds nucleotides to the 3 end to extend it. Eventually the telomerase stops, the chromosomes begin to shorten, and the cell stops dividing. Also, the telomeres act as caps, stopping the enzymes that recognize breaks in DNA; otherwise enzymes might attach two chromosomes together. Bacteria dont need telomeres because their DNA is circular. In addition to DNA polymerase having a proofreading function where it can immediately remove a base it added in error, the proteins that seam the DNA and look out for mismatched bases that havent been corrected by the polymerase. These enzymes know to correct the new strand because the new strand will have nicks (between Okazaki fragments) in the sugar-phosphate backbone.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 8

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

February 17 Continued: Chapter 11: This chapter is about cell communication and signal transduction. There are several types of communication between cells. One type is communication by direct contact between cells, whether through gap junctions, plasmodesmata, or cell-cell recognition. Another type is local signaling, where cells are not in direct contact with each other. Signaling molecules are secreted by one cell, and this signal is received by only those cells that have receptors. Paracrine signaling is from one cell to another, and autocrine signaling is a cell signaling receptors on itself. But these signals dont travel that far, making them local signals. Signals that must travel long-distance must travel through the circulatory system. The circulatory system carries the signal across the body where it can be received by receptors on cells in other parts of the body. This is called endocrine signaling. Cells respond to many signals at any given time, and must integrate the information it receives from all signals in order to decide upon a course of action. There are 4 main types of receptors. Intracellular receptors may be located in the cytoplasm or the nucleus. Ion channel receptors are rather self-explanatory, the receptors of neurotransmitters are often ion channels. There are G-protein-linked receptors, and protein kinase receptors that add phosphate groups. Can you fill in the blanks? Reception, Transduction, and Response.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 9

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

February 22 Notes: There are two main types of signaling molecules. Polar signals attach to membrane-bound receptors, as they cannot get across the plasma membrane. Non-polar signals can cross the membrane, and are received by receptors inside the cell. Signals change the shape of the receptor. This shape change dictates a change in function, usually activating the receptor-protein, causing a response to the signal by the cell. There are several types of signaling molecules, within the polar/non-polar categories. Polypeptides are polar, and bind to surface receptors. Amino acid derivatives, such as tyrosine and epinephrine, are usually not lipid soluble either. Steroids such as cholesterol, however, are lipid-soluble and can diffuse freely through the plasma membrane. A steroid hormone binds to a receptor to become a hormone-receptor complex. Often this receptor, when activated, is a transcription factor that transcribes DNA into mRNA. This mRNA is translated by ribosomes into new protein. This process, however, is a relatively slow response to a signaling molecule than a cells response to a polar signaling molecule would be. Steroid hormone responses arent developed for a while, from 30 minutes to a couple hours. Ion channel receptors involve gated channels that open when a ligand (signaling molecule) is present. Ligands are soluble secreted molecules. The entering ions cause a cellular response. Ligand binding is reversible after a while, it diffuses away, inactivating the receptor. Signal transduction can be defined as the process by which a signal on a cells surface is converted to a specific cellular response. The series of steps is a signal transduction pathway. The complexity of signal transduction pathways allow for branching, integration, and coordination in the response of a cell. The cell response can involve metabolic enzymes in altering metabolism, gene regulatory proteins in altering gene expression, and cytoskeletal proteins in altering cell shape or movement. The cell responds to signaling molecule binding by altering the function of one of these proteins, whether by altering the function of the actual protein (faster) or by altering protein synthesis (slower but more deliberate and effective). Both responses can be conducted simultaneously. G-protein-linked receptors are threaded through the plasma membrane 7 times. These interact with G-proteins, which become active by binding GTP (guanine triphosphate) when they bind to an activated

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 10

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

receptor. G-protein receptors have similar structures but may bind different ligands and Gproteins. The activated G protein binds to an enzyme, which causes a further cellular response. Then the G-protein removes the phosphate group from its GTP, shutting itself off. The Gprotein causes a second response: one possible response is a concentration of cyclic cAMP, a second messenger. High concentrations of cAMP can activate protein kinases that phosphorylate various cellular objects, altering their function. This works similarly with other secondary messengers too, that cause varying cellular responses. Signals can be amplified: 1 ligand binding to one G-protein-linked-receptor can lead to the activation of many G-proteins. Each G-protein activates an enzyme allows for the production of many second messengers, which in turn can activate many proteins which bring about that cells response. Phosphodiesterase can terminate the signal by later turning the cyclic AMP back into normal AMP. The number of cyclic nucleotides present in the cell depends on the balance of activated cyclases and activated phosphodiesterases.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 11

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 12

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

February 24 Notes: Although signals are important, they must be terminated as needed. Termination can involve the signaling molecule diffusing away from the receptor. The receptor assumes its inactive conformation. G-proteins hydrolyze its bound GTP into a GDP, releasing a phosphate group leaving a GDP. The G-protein will no longer be able to bind to the enzyme, which will become inactive and no longer generate its second messenger. The second messengers are destroyed by enzymes such as phosphodiesterase that turn cAMP into AMP. Proper and rapid termination of a signal is as important as is the arrival and activation of a signal. Phosphorylation cascades phosphorylate proteins to activate them. There are 520 different protein kinases in the human genome, some of which can put phosphate groups on other kinases, and others put phosphate groups on various proteins in the cell. A phosphorylation cascade involves a relay molecule activating a protein kinase, which phosphorylates and activates more kinases, which phosphorylate more, which eventually phosphorylate the target protein itself. This cascade allows the signal to be amplified. This pathway is rapid because it involves only minor modification to existing proteins instead of

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 13

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

taking the large amount of time it would take to synthesize new ones. Phosphotases terminate this signal by dephosphorylating the kinases and proteins. So just as there is a balance between adenylyl cyclases and phosphodiesterases, there is also a balance between kinases and phosphotases. There are around 150 different protein phosphotases. Phosphorylating proteins can inactivate certain proteins while activating others. For example, epinephrine causes cAMP to activate kinases, which phosphorylates a glycogen phosphorylase enzyme that breaks down glycogen into glucose, while inactivating glycogen synthase. Calcium is a common secondary messenger. It is normally kept in large quantities outside of the cell and inside the endoplasmic reticulum through calcium pumps and sodium-driven calcium exchangers. But gated ion channels, when activated, can allow calcium to flow quickly down its concentration gradient into the cell, activating/deactivating other proteins that are responsive to calcium. There is a calcium-binding molecule in the cytoplasm. One G protein activates a phospholipase, which can cut phospholipids from the cell membrane and use components of them as second messengers. One example is inositol triphosphate, which acts as a second messenger while leaving its glycerol tail in the membrane as a signal itself. Inositol triphosphate opens gated calcium channels on the endoplasmic reticulum, which in turn activate other proteins. Messengers are defined as molecules or ions that take the message that a signal has arrived at the plasma membrane into the interior of the cell. They are generally small and soluble, and they travel (diffuse) through the cytoplasm to their targets. Receptor tyrosine kinases have enzymatic activity. When a signal molecule arrive, two of them come together to form a dimer and phosphorylate each other in autophosphorylation. Relay proteins can then attach to the phosphate groups on the tyrosine ends on both of them, and are activated by the phosphates. One such signaling molecule is a growth factor, which binds to tyrosine kinases, which phosphorylate each other and form a dimer, which activate adaptor proteins, which in turn activate other proteins, which activate more of a phosphorylation cascade that eventually causes a greatly amplified cellular response. Phosphorylation cascades can terminate in the modification of existing proteins or terminate with new gene transcription. These cascades can be greatly varied, and cause many different things, depending on the signal. Pathways can lead to a single response, branch, cross, or be completely different with a single signal, depending on the receptor and the cell. Each cell responds differently to the same ligand, depending on the proteins in the cells. Cells respond to many different signaling molecules, integrating information. A liver cell responds to epinephrine by breaking down its glycogen deposits. Skeletal muscle blood vessels dont have glycogen, instead dilating their skeletal muscle blood vessel when epinephrine is received by the same receptor as the one in the liver cell. A different receptor, in an intestinal blood vessel, constricts the blood vessel. Epinephrine stimulates 9 distinct G-protein-linked receptors, each of which can cause different effects depending on their place.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 14

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 15

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 16

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 17

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

March 1 Notes: Cells of multicellular organisms are committed to collaboration. To coordinate their behavior, the cells send, receive, and interpret an elaborate set of signals that serve as social controls, telling each other how to act. As a result, each cell behaves in a socially responsible manner, resting, dividing, differentiating, or dying, as needed for the good of the organism. Disturbances that upset this harmony mean trouble for a multicellular society. Many mammalian cells require both soluble signals and signals from the extracellular matrix to grow and proliferate. Cells need signaling just to survive. Indeed, the absence of signaling from other cells can often lead a cell to commit suicide. The combination of signals a cell receives dictates the cells behavior, allowing it to survive, divide, differentiate, or die. Other cells can directly signal a cell to commit suicide. Absence of signaling usually causes a cell to commit suicide, as does receiving death signals or engagement of cell surface death receptors. If cells stop behaving in a socially responsible manner, they must die. Cancer is a disease in which an individual mutant clone of cells prospers at the expense of its neighbors. Mutations that promote such selfish behavior by individual members of the cooperative can jeopardize the future of the entire enterprise. Cancer is a disease in which an individual mutant clone of cells prospers at the expense of its neighbors. It takes the lions share of the nutrients and doesnt listen to cues that would tell the cell that it is too crowded to divide. Cancer cells also manipulate the cells around them to set them to release the signals that the cancer cell requires. Cancer occurs when cells become selfish and unwilling to kill themselves. By the time a typical human tumor is detected, it will have been developing for many years and will contain about a billion cancer cells or more. Mitogens encourage cells to undergo mitosis, and are needed to drive the cell cycle. Growth factors help newly-divided cells grow, and activate nutrient uptake and utilization in the growth of the cell. There are checkpoints in the cell cycle

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 18

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

that must be passed in order to continue in the cell cycle. There is a checkpoint just before mitosis, during mitosis, and in the first gap (G1) after mitosis before DNA synthesis. The G1 checkpoint is passed only if the cells size is adequate, nutrient availability is sufficient, growth factors are present, and DNA is undamaged. The G2 checkpoint ensures that DNA replication in S-phase synthesis was successful. There is another checkpoint in mitosis to ensure that all the chromosomes have been properly attached to the mitotic spindle before the spindle shortens and chromosomes are partitioned. The cell is committed to fixing damage before progressing through these checkpoints. However, if damage is too severe, the cell is obligated to commit cellular suicide. Each type of cancer is caused by a different set of defects that lead to uncontrolled cell growth. Cancer results from defects in proteins that control the cell cycle and are involved in maintaining chromosomal stability. It is associated with mutations that knock out key genes. Cancer results from defects in genes that code for proteins that are involved in regulating the cell cycle and genes that are involved in ensuring quality control. In some cases, the resulting proteins gain excessive function and in other cases the mutations lead to proteins that have lost function. Cancer is initiated when a mutation leads to abnormal proliferation of a single cell. Another mutation might occur, giving the newly mutated cell additional advantages. Progression occurs as more mutations accumulate. Cells that divide or survive faster/better are selected for. Development of cancer typically requires that a substantial number of independent, rare genetic accidents occur in the lineage of one cell. Normal cells respond to signals that stimulate cell growth and division, inhibit cell growth and division, and initiate programmed cell death. 7 key properties make cell capable of cancerous growth. They disregard the external and internal signals that regulate cell proliferation. They tend to avoid suicide by apoptosis. They circumvent programmed limitations to proliferation, escaping replicative senescence and avoiding differentiation. They are genetically unstable. They escape from their home tissues, are invasive. They can survive and proliferate in foreign sites, metastasize. They induce help from nearby cells, through angiogenesis. Normal cells require growth factors in order to proliferate. In basic growth medium, platelet-derived growth factor and mitogens are required for normal cells to divide, until they reach replicative senescense (Hayflick limit). But cancerous cells can often grow in basic growth media alone, with limited needs, and dont have a Hayflick limit. They are immortal, and lose density-dependent inhibition of division, dividing even when crowded. Of course, division is still going to be based on nutrient and gas availability. When cells have gained a division advantage over their neighbor, they might still be benign in an epithelium, unable to break through into connective tissue. Once they break through basal lamina, they can invade the capillary. Once it travels through the bloodstream, one can adhere to a cell membrane in a different organ and invade the new organ. This cancer will grow much as the first. After I emailed out my notes before the first midterm, Alaie decided she didnt like my descriptions of her jokes. Instead, I will be putting jokes of mine, and other stories of my week, to punctuate the boringness of endless pages of Biology notes. So, for March 8 Notes: In invasion, a cancer escapes through the basal lamina of a tissue into a capillary. The cells travel through the bloodstream. Metastasis occurs if the cancer cell is able to escape from the blood vessel and proliferate in a different, new area of the body. This is a

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 19

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

challenge because different areas of the body have cells that secrete different things, and might not secrete the growth hormones that the cancer is used to. Cancer karyotypes are also abnormal. Tumor cells take on new chromosomes, throw off chromosomes, and combine chromosomes. There are three classes of genes that, when mutated, disrupt the cell cycle and trigger uncontrolled cell growth: 1. Proto-oncogenes genes that trigger cell growth and division by initiating specific phases in the cell cycle. These genes are like the gas pedal that tell the cell to continue dividing or growing. A mutated oncogene is like a stuck gas pedal. But even proto(normal) oncogenes dont stop the cell cycle, much as a gas pedal cannot act as a brake. There are many different proto-oncogenes. Every type of molecule involved in cell signaling can be mutated into an oncogene. The (genes that produce) proteins that produce a secreted protein are proto-oncogenes. Genes that produce transmembrane receptors, GTP-binding proteins, and protein kinases are proto-oncogenes, as are genes that code for regulatory proteins such as transcription factors, proteins involved in gene expression, and proteins (e.g. cyclins) that directly stimulate the cell cycle. There are more than 100 different cancer-critical genes that can be converted from protooncogenes into oncogenes by an activating mutation that either makes the gene in excess or makes the gene hyperactive. This mutation can occur through: a) Translocation or transposition, moving the gene to a new locus, under new controls with a new promoter, which now makes this growth-stimulating protein in excess. b) Gene amplification, where multiple copies of the gene are made in the DNA, also causes normal growth-stimulating proteins to be created in excess. c) Point mutation within a control element also causes normal growth-stimulating proteins to be created in excess. d) Point mutation within the gene itself, while not making the protein in excess, might make an abnormal protein, perhaps making it hyperactive (constantly turned on) or degradation-resistant. 2. Tumor suppressors genes that stop or slow the cell cycle in the presence of DNA damage, lack of nutrients, or otherwise unfavorable conditions for cell cycle progression. These genes also can initiate apoptosis, programmed cell death. The tumor suppressor is the brake pedal of the cell. A loss of a tumor suppressor means that the cell has no brake pedal. The loss of both copies (in both alleles of DNA) is usually required for a loss of function of the tumor suppressor. Tumor suppressor gene loss occurs through: a) Point mutation that inactivates the allele. b) Deletion of the gene due to error in replication c) Loss of chromosome due to nondisjunction d) Epigenetic silencing of the promoter for the tumor suppressor gene wrapping into heterochromatin or another inexpressed form of DNA. e) Viral proteins, which wrap around the genes, transcription factors, and others, preventing this gene from functioning. Most tumor suppressors are negative cell cycle regulators. Some tumor suppressors block the cell cycle in the presence of DNA damage or incomplete DNA replication. In their absence, cells with damanged DNA keep generating new cells without fixing the damage. ARF, p16, pRb, p53, and p21 block the G1 S checkpoint. Rb blocks S G2.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 20

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

And p21 blocks M from starting. Tumor suppressor p53 is a transcription factor that regulates the expression of several important cell cycle regulatory genes, such as p21, that prevents the onset of S-phase, and proteins that are essential for the repair of DNA. It also controls the expression of proteins that are used for apoptosis, controlled cell death if DNA damage is irreparable. When p53 is stabilized, by hyperproliferative signals, DNA damage, telomere shortening, or a lack of oxygen, p53 transcribes proteins that cause cell cycle arrest, senescence, and/or apoptosis will be activated. Disability of p53 allows the cell cycle to continue without arrest, dividing with damaged chromosomes. Either mitotic failure will occur, the cell will die and the tumor will regress, or replication will be successful, and survive to continued mutation, selection, and tumor evolution. Retinoblastoma, also known as Rb, is another tumor suppressor. A normal, healthy individual has two alleles of Rb. Occasionally, a cell will inactivate one of its two genes. In hereditary retinoblastoma, a mutant Rb gene is inherited. Occasionally, one of these cells will inactivate an Rb, in this diseased case its only good gene copy. A cell without any good Rb genes will replicate excessively, leading to retinoblastoma. So a predisposition for cancer can be hereditary, although actual cancers are not. Such people with such a predisposition are more likely to have tumors develop, possibly at young ages. But tumor suppressors are not only knocked out by mutations in the tumor suppressor alleles. Several DNA viruses are cancer-causing because they make proteins that inhibit tumor suppressors. Their DNA is incorporated into the cell genome. Viral protein E7 prevents Rb from doing its normal function of binding a cell proliferation factor. Viral protein E6 inactivates and destroys p53, preventing it from transcribing p21, making the cell actively proliferate with the virus contained in it. 3. DNA maintenance genes genes that maintain genomic stability. Mutations of them contribute to cancer formation. All three of these genes are normally healthy proto-oncogenes are not diseased genes. Normally, with the help of signals, they tell the cell when to grow. Tumor suppressors act as brakes to stop tumors from occurring. March 10 Notes: A large section of tonights notes are written into Tuesdays numbered list, particularly #2. Normally, in an epithelial layer, there is only a very restricted outer layer that continues to divide. In a low-grade intraepithelial neoplasia, the lower-level cells begin to divide. In high-grade intraepithelial neoplasia, all the cells are dividing but doesnt break the basal lamina, and a true malignant carcinoma can metastasize. The multiple hit model of cancer formation: in colon cancers, first a tumor-suppressor is lost, gene APC, creating a polyp while the ras oncogene is activated. Once another tumor-suppressor gene is lost, it becomes a larger but still benign adenoma, as p53 is lost. Additional mutations will lead to a malignant tumor, a carcinoma. For a cancer to occur there must be a loss of function in several tumor suppressor genes as well as a gain of function in several oncogenes. It must sustain around 12-15 mutations before the cell becomes fully cancerous. Such additional mutations include genes that are involved in DNA repair that contribute to cancer formation when they get mutated. Cancer cells develop the ability to stimulate the growth of new blood vessels in angiogenesis. Telomerase can become activated, whether in the process of becoming cancerous or once already cancerous. And although stem cells have similar properties to cancer cells (e.g.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 21

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

immortality and telomerase), not every cancer cell is a stem cell. Some cancer cells were once normal somatic cells that just turned their telomerase on and dedifferentiated. The immune system doesnt wipe out the tumor cells because many cancerous cells produce the same proteins and signals as any other normal cells, preventing them from being recognized by the immune system. Tumor cells may stop expressing the one MHC I allele that presented an altered peptide, although it still expresses its 5 other MHC I alleles. Tumor cells do not express the proper cytokines or co-stimulatory molecules to activate nave CD8 cells. Chapter 45: Together, the nervous system and the endocrine system coordinate functions of all the body systems. The nervous system controls body activities through nerve impulses that result in the release of signaling molecules at synapses with other cells. Synapses are small spaces between two cells. Neuron communication is electrical, with electrical charge travelling the length of an axon much faster than a hormone travelling through the bloodstream. The glands of the endrocrine system release signaling molecules, hormones, into the bloodstream. The circulating bloodstream then delivers hormones to virtually all cells of the body. Only cells with receptors are target cells, and only they can respond to the signal. This is not a direct connection; the movement is sent across a transportation system, the blood. The nervous and endocrine systems respond to a stimulus at different rates. Nerve impulses most often produce an effect within milliseconds. Some hormones can act within seconds whereas others can take several hours or more to cause a response. Some hormones can act within seconds while others can take hours to cause a response. These differences are caused partially by differences in effects of the hormone; epinephrine causes a phosphorylation cascade, which is much faster than new gene transcription. All hormones fulfill the same general role: to coordinate the activities of diverse groups of cells in response to changes in the external or internal environment. Many different hormones are coursing through your circulatory system right now. The hormones are regulating the maturation of sperm or eggs by your reproductive system, changing the composition of urine formed in your kidneys controlling the release of digestive enzymes in your gastrointestinal tract, and maintaining homeostasis. Animals tend to maintain relatively constant conditions in their internal environments even when the external environment changes. We like a temperature of around 37 degrees C, a pH of around 7.35, and a blood sugar level of 0.1%. Homeostasis is an internal balance, a dynamic state between outside forces that tend to change the internal environment and internal control mechanisms that oppose such changes.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 22

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 23

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

March 15 Notes: Hormones can be released by: 1. Nervous system both the hypothalamus and the adrenal medulla secrete hormones in response to stimulation from the nervous system. 2. Hormones can stimulate the release of other hormones. 3. Chemical changes in the blood the concentration of certain ions or sugars can lead to the release of hormones.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 24

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

The hypothalamus is the major integrating link between the nervous system and the endocrine systems. It receives input from other regions of the brain while also receiving sensory signals from internal organs. The hypothalamus regulates body temperature, thirst, hunger, sexual behavior, and defensive reactions such as fear and rage. The hypothalamus is an important regulatory center of the nervous system and is a crucial endocrine gland. Neurosecretory cells stretch from the hypothalamus to the posterior pituitary. The posterior pituitary contains axons of more than 10,000 neurons whose cell bodies are in the hypothalamus. Two neurosecretory cells: the supraoptic nucleus cells secrete oxytocin. Paraventricular nucleus cells secrete ADH (anti-diuretic hormone). In the posterior pituitary, flood flows through axon terminals which release hormones into capillaries of the capillary bed. There are around 10,000 neuron axons in the posterior pituitary whose cell bodies are in the hypothalamus. They transport hormones from the hypothalamus into the bloodstream. The hypothalamus oxytocin targets, among others, mammary glands and uterine muscles, to eject milk during nursing and contraction during labor. Its ADH targets kidney tubules, which activate aquaporins, causing water to be reabsorbed. People with low ADH have diabetes insipidus, causing them to urinate in vast quantities and must be careful not to dehydrate. Although the hypothalamus is directly connected to the posterior pituitary, it is not directly connected to the anterior pituitary. The anterior pituitary releases its hormones when it receives hormones from the hypothalamus. Normally, the arteriole takes blood from the artery to arterioles, which go to capillaries that feed the various cells, which return the used blood to the venules, which go back to the veins. The anterior pituitarys first part with axons from the hypothalamus has capillaries that bring blood through the portal veins, straight to the anterior pituitary part that houses endocrine cells, and capillaries return the newly hormone-filled blood to a vein. So the hypothalamus controls the release of hormones from the anterior pituitary by releasing its own hormones. The hypothalamus both allows and inhibits hormone release by the endocrine system. The anterior pituitary releases: 1. ATCH targets adrenal cortex, causing the production of glucocorticoids. 2. Follicle-stimulating hormone and luteinizing hormone targets testes or ovaries, causing production of sex hormones and controls the menstrual cycle. 3. Growth hormones target bones, causing growth. 4. Prolactin targets mammary glands, causing mammary gland growth and milk production. 5. Thyroid-stimulating hormone targets the thyroid, causing the production of thyroid hormones. Tropic hormones target other endocrine glands. Non-tropic hormones target non-endocrine glands. Multiple feedback loops control hormone secretion. External conditions influence the hypothalamus, releasing a hormone that causes the anterior pituitary to release a tropic hormone, targeting an endocrine gland to release another hormone. The final hormone longloop-inhibits the anterior pituitary ad the hypothalamus. The tropic hormone short-loopinhibits the hypothalamus. One example of this is cold exposure, which influences the hypothalamus to produce thyrotropin-releasing hormone, which causes the anterior pit to release thyrotropin, which causes the thyroid to produce thyroxine. Thyroxine inhibits the hypothalamus and the anterior pit, while it binds to target cells. The body can convert thyroxine to triiodothyronine, which is a more active form. The adrenal gland sits on the kidney. The cortex wraps on the medulla, and holds 80% of the mass of the adrenal gland. The

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 25

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

hypothalamus releases CRF (corticotrophin-releasing factor), which causes the anterior pit to release ACTH (adreno-corticotropin hormone), causing the adrenal cortex to release cortisol. Glucose homeostasis is maintained by insulin and glucagon. Rising blood glucose level, from eating or other stimuli, stimulates the beta cells of the pancreas to release insulin into the blood. Insulin causes body cells to take up more glucose, and has the liver take up glucose and store it as glycogen. These two responses cause the blood glucose level to decline to a set point, and the stimulus for insulin release diminishes to homeostasis, a normal blood glucose level. When the blood glucose level is low, e.g. after skipping a meal, the alpha cells of the pancreas are stimulated to release glucagon into the blood. Glucagon causes the liver to break down glycogen and release glucose to the blood. The blood glucose level rises to homeostasis, and the stimulus for glucagon release is diminished. These two pathways oppose each other.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 26

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

Note on figure 45.8: the text is a little off from the picture. So that its clear, FSH/LH affect the testes/ovaries, TSH affects the thyroid, ACTH affects the adrenal cortex, prolactin affects the mammary glands, MSH affects the melanocytes, endorphins affect the pain receptors in the brain, and growth hormone affects the liver and bones. All text should be shifted to the right about half an inch.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 27

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

March 17 Notes: Graves disease is caused by hypothyroidism, where the thyroid hormones are oversecreted. The posterior pituitary is the one directly attached to the hypothalamus. Anterior pituitary hormones are created in the pituitary itself while the posterior pituitary secretes hormones produced by the hypothalamus. Insulin is very polar. Insulin receptors are needed to transduce the signal into the cell. Insulin receptors on fat cells and muscle cells adjust the concentration of glucose transporters in the plasma membrane. The signal transduction pathway causes glucose transporters to be brought (via vesicle) from a vesicle full of them to the plasma membrane. Insulin-dependent diabetes mellitus is an auto-immune disorder, destroying the beta cells of the pancreas that produce insulin. It requires regular injections of insulin, as otherwise glucose will not enter the cells. In this disease, glucose is found in the urine. Diabetes mellitus type 2 is non-insulin-dependent. Despite having plenty of insulin, target cells may be less sensitive to insulin due to down-regulation of insulin receptors. Chapter 46: Sexual reproduction has been favored by evolution probably because the random recombination of genetic information improves the chances of producing at least some offspring that will survive in an unpredictably variable environment. Meiosis is reductive division, halving the number of chromosomes in each gamete (but making 4 of them) and allowing them to recombine into diploid during fertilization. Sister chromatids fuse, with chiasma switching parts of the nearest chromatids in the tetrad, before they split twice into 4 haploid gametes. Human females are born with all the eggs that they will ever have. The germ cell in the embryo differentiates and forms an oogonium in mitotic division. The primary oocyte is formed before the woman is born, between 3 and 8 months of gestation. At puberty, under the influence of a rise in gonadotropin-releasing hormone from the hypothalamus, the anterior pituitary starts releasing its gonadotropic hormones (Follicle Stimulating Hormone, Luteinizing Hormone). These hormones allow 1 cell per month to finish meiosis 1 and get arrested in meiosis 2s metaphase. It will be released from the ovary in ovulation. If this cell is not fertilized by a sperm, it will never complete meiosis 2 and will be released from the body during monthly menses. If a woman has not had an egg fertilized, no egg has ever completed meiosis 2. Cytokinesis is asymmetrical during gametogenesis in females. Cytoplasm is to be given to one egg and the other polar bodies degenerates. The entry of sperm triggers the completion of meiosis 2. Cyclical changes in the ovary: 1. 2. 3. 4. 5. Formation of primary oocytes within follicles Follicle growth Maturation of follicle Ovulation Degeneration of corpus luteum what is left after the secondary oocyte leaves is a yellow body that dies.

In the first half of a cycle, the follicular phase, Follicle Stimulating Hormone (FSH) helps the oocyte-containing follicle to grow. Estrogens are produced as the follicle grows, to repair the uterine lining and stop the blood release, in preparation for the egg to enter it. Estrogen also inhibits the anterior pituitary from releasing FSH, preventing another follicle from growing. Estrogen simultaneously positively regulates LH production, causing a luteal surge which gives

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 28

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

the final push for the egg to leave in ovulation into the uterus, after which the empty follicle degenerates. This is the midpoint of the cycle.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 29

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

March 22 Notes: The luteal surge is caused by a peak in estrogen, when there is a spike in the luteinizing hormone produced. The egg is ovulated into the uterus, where it has 24-48 hours to be fertilized before it is no longer viable for fertilization. The sperm have around the same length of life. The egg that was released from the mature follicle has completed meiosis 1 and is now referred to as a secondary oocyte, arrested in metaphase 2, during menses when the uterine lining is shed. The egg is surrounded by protective cells in the uterus, while the decomposing corpus luteum (eggless follicle) releases moderate levels of estrogen and high levels of progesterone. Progesterone helps attract sperm, while both hormones continue to ready the lining of the uterus for possible implantation of an egg following fertilization. Therefore, the best time to implant is approximately a week after fertilization, when the fertilized zygote actually arrives in the uterus from the oviduct. High levels of progesterone and moderate levels of estrogen exert negative feedback on FSH and LH and inhibit growth of additional follicles (with maturation of their eggs) during the luteal phase. Some LH is necessary to keep the corpus luteum viable but too much FSH or LH is wanted because new follicles would grow in their presence. The corpus lutem begins to degenerate at day 24 if it doesnt receive signals from the implanted balls of cells (blastocyst). If there is an implanted blastocyst, then human chorionic gonadotropin (HCG) is released. This is a pregnancy hormone, secreted to keep the corpus luteum intact and secreting more progesterone, and is tested for in urine to find pregnancy. In the absence of HCG, levels of progesterone and estrogen drop off, the corpus luteum will degenerate, and the uterine lining will be shed, restarting the cycle again from day 0. Human males, unlike females, do not begin meiosis before birth. Indeed, meiosis does not begin until puberty increases the concentration of GnRH released from the hypothalamus. Under GnRH influence, the anterior pituitary releases FSH and LH. Male reproduction is controlled by these hormones, too. LH targets Leydig cells, which produce testosterone. Testosterone, along with FSH, target Sertoli cells, which stimulate spermatogenesis in the spermatogonium as well as inhibin, which inhibits the hypothalamus and anterior pit. Mitosis begins at puberty, producing a large number of spermatogonia that are the sperm mothers. Meiosis takes 24 days, forming secondary spermatocytes after meiosis 1, becoming spermatids after meiosis 2. Differentiation from round spermatids to fully differentiated swimming sperm cells takes 5 weeks or more, as they rid themselves of most of their organelles. Sertoli cells support the spermatogonium and provide the sperm with the needed nutrients, making the sperm cells streamlined for their task of delivering a haploid nucleus, a pair of centrioles, and a relatively small number of mitochondria. Male reproductive years begin at puberty and often extend throughout the lifespan. This production of sperm occurs in the seminiferous tubule, before they must be trained in motility in the epididymus (coiled tubules located on top of the testes. Female cytokinesis is asymmetrical. Male cytokinesis is incomplete, without splitting, keeping cytoplasmic bridges from which mature spermatozoa emerge (leaving residual bodies).

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 30

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 31

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 32

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 33

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 34

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 35

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

March 24 Notes: Semen is only partially sperm, also containing seminal fluid. This contains/is produced by: (Alaies slide):

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 36

BIOL102 Notes Professor Adrienne Alaie


Semen = Sperm + Seminal Fluid
Source
Seminal Vesicles (60% of volume) (alkaline fluid)

Spring 2011

Content
Fructose (for ATP production) Prostagladins (stimulate smooth muscle contractions in uterus; contribute to sperm motility and viability) Clotting proteins Antibiotic Compounds (seminalplasmin) Citric Acid (for ATP production) Proteolytic Enzymes: Pepsinogen prostrate specific antigen (PSA), lysozyme, amylase: break down clotting proteins from seminal vesicles

Prostrate Gland (25% of volume) Slightly acidic pH ~ 6.5

Bulbourethral Gland (or Cowpers Glands)

Alkaline Mucus (protects the passing sperm by neutralizing acids from urine in the urethra)

Overall pH of ~ 7.2-7.7

1. Seminal vesicle contain fructose (for ATP production), prostaglandins, and clotting proteins. 2. Prostate gland see Alaies slide. As of this notes press time, this slide had not yet been posted. It secretes its products directly into the urethra via several small ducts. 3. Bulbourethral gland more will probably be on Alaies unreleased slide that I will ask for in the next class (UPDATED 4/7 pasted above). It secretes a clear mucus before ejaculation that neutralizes the acidic urine in the urethra, paving the way for the basic semen. The egg is fertilized in an acrosomal reaction. The sperm first binds to the zona pellucida, the protective layer of the egg. This binding stimulates the acrosomal vesicles in the sperm to be released. The acrosomal vesicles contain hydrolytic enzymes that help to digest through the protective coating in order for the sperm to reach the plasma membrane of the egg. Around 100 sperm must undergo the acrosomal reaction, releasing their hydrolytic enzymes, to digest the protective coat and reveal the plasma membrane. Once the plasma membrane is revealed, one sperm fuses with the plasma membrane. Once the sperm has fused, the cortical reaction occurs. Calcium-filled vesicles, cortical granules in the egg release their contents (including hydrolytic enzymes) to change the composition of the zona pellucida (partially by altering the shape of the ZP3 connective protein in the zona pellucida to make it impenetrable by more sperm). Upon fusion of the egg and sperm, the cortical reaction occurs and the egg and sperm pronuclei come together and the DNA in each pronucleus is copied. The nuclear membranes break down and the chromosomes are now placed on the first mitotic spindle. This spindle is set up in the center of the cell and the first division occurs within 24 hours of fertilization. When the egg is fertilized, it moves along the fallopian tubes to the uterus. A blastocyst is formed by

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 37

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

day 5, the beginning of differentiation with both outer and inner cell layers. Stem cells are taken from the inner layers. Chapter 43: There are two types of immunity to invading microbes: 1. Innate immunity non-specific immunity. It is rapid responses to a broad range of microbes. Innate immunity is always active, protecting us and fighting in a general, nonspecific way, against infectious microbes. It involves two types of defenses, external and internal defenses. External defenses passively defend against everything entering: a) Skin the skin is a continuous layer that defends against any microbes from going through it unless it is punctured. b) Mucous membranes these coat the openings of our body, preventing microbes from entering through it. Examples include the mucous surrounding cilia in our respiratory system, that sweep pathogens out. c) Secretions the acidity of human body secretions, such as saliva, the stomach acid, and the various membranes around the body, helps destroy many microbes that cannot tolerate acidity. d) Mucus secretions trap bacteria and other pathogens in digestive and respiratory tracts e) Nasal hairs filter bacteria in nasal passages f) Cilia move mucus and trapped materials away from respiratory passages g) Gastric juice concentrated HCl and proteases destroyed pathogens in the stomach. h) The vagina is acidic, limiting the growth of fungi and bacteria in the female reproductive tract. i) Tears and saliva they lubricate and clean; their acidity prevents unwanted microbes from entering. Internal defenses include cells considered generalists along with antimicrobial proteins: a) Phagocytic cells b) Antimicrobial proteins complement proteins, 20 of them in a phosphorylation cascade that together form a membrane attack complex. This membrane attack complex punches a hole in a bacterial cell membrane, allowing everything to enter, killing the cell. c) Inflammatory response d) Natural killer cells e) Macrophages f) Dendritic cells g) Neutrophils 2. Acquired immunity specific immunity, adaptive system. It involves slower responses to specific microbes. Two examples of acquired immunity include: a) Humoral response B cells, antibodies that circulate in the bodily fluids. b) Cell-mediated response T cells, cytotoxic lymphocytes. These are active killer cells that are manufactured in large quantities in order to destroy a specific pathogen. But they take a while to manufacture, and are not constantly active.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 38

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 39

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

March 29 Notes: In addition to the specific immune attack cells, there are immune system proteins that complement each other to form a membrane attack complex that punches a hole in the plasma membrane of a foreign cell. There are a few different cells, and ways that these cells are created:

Pluripotent stem cells in the bone marrow are the stem cells that create many different types of immune system cells. It divides, giving rise to lymphoid and myeloid stem cells. Lymphoid stem cells give rise to the B lymphocytes that gives rise to the plasma cells, the thymus that

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 40

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

gives rise to the T lymphocytes, and the NK lymphocytes. The myeloid stem cells give rise to the erythrocytes, megakaryocytes that give rise to platelets, monocytes that give rise to macrophages, granulocytes, and dendritic cells. Normally, red blood cells greatly outnumber white blood cells, on the order of 700 to 1. White blood cells are cells of the innate immune system, and include basophils, eosinophils, neutrophils, monocytes that develop into macrophages, dendritic cells, NK cells, and others. (Alaies slide): Type of cell Function
Red blood cells (rbc)
Platelets (cell fragments)

transport oxygen and carbon dioxide


involved in blood clotting

White blood cells (leukocytes): Cells of the innate immune system:


Basophils
Eosinophils Neutrophils Monocytes

Release histamine, leukotrienes


Release enzymes/ effective against parasitic worms Release histamine/ phagocytize bacteria

develop into
Macrophages Engulf and digest microorganisms; activate T and B cells Present antigens to T cells Release histamine, leukotrienes Attack and lyse abnormal body cells

Dendritic cells Mast cells Natural Killer (NK) Cells

Those cells are found circulating in the blood. But they are also brought into the blood from the lymphatic capillaries. The lymphatic system runs parallel to the blood system. Lymph gets between the blood and the lymphatic system through the interstitial fluid. At lymph nodes, the lymph capillaries have openings through which lymph can flow. In the lymphatic system, lymphatic capillaries merge into larger vessels and ultimately into two lymphatic vessels: thoracic ducts that empty into large veins at the base of the human neck. The left thoracic duct carries most of the lymph from the lower part of the body. Interfaces between the lymphatic system and the circulatory system are present at underlying tissue where pathogens might gain entry to the body, such as in the lungs and the intestines. Other lymph nodes include adenoids, tonsils, thymus, spleen, Peyers patch in the small intestine, the spleen, and the appendix. Thus, the innate immune system can police the entrances to the body with macrophages, mast cells, and dendritic cells. These cells can release chemicals that bring neutrophils, basophils, cosinophils, and perhaps cells of the adaptive immune system from the blood to the spot where the pathogen is encountered. Two broad categories of cells known as lymphocytes (B and T cells) can circulate not only in the blood vessels but also in the lymphatic system. These cells can therefore police the entire body. When B and T cells pass lymph nodes, they have the chance to inspect other immune system cells, destroying any pathogens that are brought to the lymph nodes. Innate immune system cells bring their pathogens to these highway bars for presentation. If B and T cells can bind the shape of the molecule being presented, they are

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 41

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

retained in the lymph node and undergo clonal expansion division. Macrophages, neutrophils, and other innate cells are considered non-specific because they express receptors for many bacterial constituents. Once they bind one of their many possible pathogens, they migrate to a lymph node, and present the pathogen to the specific B or T cell that can remove the pathogen. Binding of bacteria to the macrophage receptor initiates the release of cytokines and small lipid mediators of inflammation. Macrophages engulf and digest the bacteria to which they bind. The bacteria are digested inside the macrophage when their endocytotic vesicles that engulf the macrophages fuse with lysosomes that digest the bacteria. Fragments of the digested pathogens can then be presented by the innate immune cell to the adaptive immune cells. Neutrophils kill themselves when they bind pathogens. They secrete their own chromatin to trap bacteria in a sticky web. Ill probably have a picture to show this, but heres Alaies list for the inflammatory response: 1. Bacteria and other pathogens enter the wound. 2. Mast cells secrete factors that mediate vasodilation and vascular constriction. Deliver of blood, plasma, and cells to the injured area increases. 3. Macrophages secrete hormones called cytokines that attract immune system cells to the site and activate cells involved in tissue repair. 4. Platelets from the blood release blood-clotting proteins at the site of the wound. 5. Neutrophils secrete factors that kill and degrade pathogens. 6. Neutrophils and macrophages remove pathogens by phagocytosis. 7. Inflammatory response continues until the foreign material is eliminated and the wound is repaired. Selectin-mediated adhesion is weak, and allows the white leukocytes to roll along the blood vessel walls. When cytokines are released, leukocytes slide between the stimulated selectins into the surrounding connective tissue. Cytokines attract leukocytes to their source, making leukocytes chase them.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 42

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

March 31 Notes: Some vocabulary: 1. Leukocytes are white blood cells, as opposed to ethyrocytes, red blood cells. All immune cells are leukocytes, with subcategories including NK cells, B cells, T cells, macrophages, etc.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 43

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

2. Lymphocytes are cells that circulate between blood and lymph fluid B and T cells. They check out secondary lymphoid organs, such as lymph nodes. 3. Cytokines are proteins that alter the behavior of target cells. 4. Chemokines are cytokines that alter the behavior of the target cell such that the target cell moves toward the chemokine. 5. Interleukines are signaling molecules sent out between two leukocytes or between leukocytes and non-white-blood cells. The specific/adaptive immune system has four key traits: 1. Specificity a given cells receptors will only attach to a specific type of cell. 2. Ability to respond to an enormous diversity of foreign molecules and organisms there are hundreds of thousands of these specific cells, allowing them to respond to many different pathogens. 3. Ability to distinguish self from non-self the specific immune system recognizes cells that belong in the body, only attacking foreign cells. It must be able to identify healthy self cells from infected self cells and non-self cells. Problems in this characteristic lead to autoimmune disorders. 4. Immunological memory immunity. We have long-lived immune system cells that remember a given infection in a half-activated state. Cells of the adaptive immune system include: (Alaies slide, although I had already written the contents of this slide below it): Type of cell Function
Cells of the adaptive (specific) immune system:
Lymphocytes:

B cells
differentiate into

patrol blood and lymph

Plasma cells Helper T (CD 4) cells Cytotoxic T (CD 8) cells

secrete antibodies activate B cells and Cytotoxic T cells attack and lyse virally-infected body cells

1. B cells that patrol blood and lymph 2. Plasma cells that secrete antibodies 3. Helper T cells that activate B cells and cytotoxic T cells

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 44

BIOL102 Notes Professor Adrienne Alaie


4. Cytotoxic T cells that attack and lyse virally infected body cells.

Spring 2011

Lymph nodes are interfaces between the lymphatic and circulatory system, where B and T cells inspect pathogens from the innate immune system. There are various organs in the lymphoid system: 1. Primary lymphoid organs the thymus and bone marrow, where B and T cells mature. 2. Secondary lymphoid organs the spleen and lymph nodes, where B and T cells gain experience and become activated. During activation, gene expression changes to allow the cells to achieve an activated profile where they are making toxic chemicals, signaling molecules, and/or antibodies. Once activated, they will go into circulation. 3. Lymphocytes are transported through lymphatic ducts and blood vessels. Clonal expansion: activation goes hand-in-hand with cell division. When a T cell enters a lymph node and is activated by interaction with a dendritic cell, it undergoes differentiation and clonal expansion. Many activated clones of this T cell leave the lymph node and get dumped into the blood, to be called upon as needed to fight pathogens. The helper T is also known as a CD4, after a receptor that is found on its surface. Cytotoxic Ts are also called Killer Ts or CD8s. An antigen is an antibody generator. It stimulates the production of antibodies. Each B or T cell is coated in antigen receptors but they are of a single specificity. Cells of the adaptive immune response will be selected for expansion and activation only if they can bind an antigen with their specific antigen receptor. T cells must have their antigen (peptide part) presented to their T-cell receptor (TCR) by a cell-surface glycoprotein known as a Major Histocompatibility Complex (MHC) molecule. B cells can bind free-floating antigens, whether as a peptide or an oligosaccharide or a nucleic acid. Presentation of peptides occurs in cell-surface glycoproteins known as the Major Histocompatibility Complexes, MHCs. (Alaies slide):
What cells have this MHC? What cell recognizes this MHC? Where does peptide presented in this MHC come from?

MHC I

All nucleated cells

CD8 (Cytotoxic T)

Proteins made inside the cells (endogenously-derived) are broken down and loaded into MHC I

MHC II

Professional APC: Dendritic B cells Macrophages

CD4 (Helper T)

Proteins from outside (exogenously-derived) are taken in, broken down and loaded into MHC II

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 45

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

Two classical types of MHC molecules exist, MHC 1 and MHC 2. MHC 1 are found on the surface of every nucleated cell in the body (not unnucleated red blood cells). MHC 2 are found on professional antigen-presenting cells: dendritic cells, macrophages, and B cells. MHC 1, on every nucleated cell, gets loaded with peptides and makes its presentation to cytotoxic T cells. The loaded peptides are simply normal pieces of proteins from the everyday function of a cell. Every healthy nucleated cell loads these pieces of protein, as part of their obligation to show the heath of the internal protein production. But only cells infected with virus will load viral proteins, which will be recognized by T cells. MHC 1 cells loaded with peptides present to killer T CD8 cells. MHC 2 cells loaded with peptides present to helper T CD4 cells. MHC 1 cells show their health. MHC 2-loading cells are not showing the cell health they are showing the health of the body as a whole, as these cells are absorbing peptides from the rest of the body. MHC 2 activates helper Ts, CD4s, that then activate other immune cells. Antigen presentation occurs with the CD4/8 acting as a coreceptor as the antigen is bound by the T-cells receptor. When peptides are presented by an antigen-presenting cell (APC) in MHC 2 to CD4 cells, it is done so for the purposes of activation MHC 2 peptides are exogenously derived, from outside the cell, to check the health of the body as a whole (these cells will have MHC 1 as well, to show its own health). Presentation in MHC 1 to CD8 cells is for the purpose of the CD8 checking the health. Cells have an obligation to present their peptides to CD8s. A self-peptides presentation will not be recognized by a cytotoxic T CD8 cell, but a foreign peptide will be recognized, causing cell death. When a cytotoxic T cell recognizes an infected cell, proteases are released to break down the infected cell. When a CD8 cell collides with a target cell, its toxic chemical granules are redistributed to the collision point. Once contact is again made, and the target cell is bound, the toxic granules are released from the collision point. This is done neatly, killing only the cell directly contacted. The central role of helper T CD4 cells is to help activate nave inactivated B and CD8 cells. A nave CD4 cell must get itself activated, before it can help activate others. The antigen is first taken up into a dendritic cell by phagocytosis and degraded in a lysosome. Interleukin-1, a cytokine, activates a helper-T cell. The T cells receptor recognizes an antigenic fragment bound to a class 2 MHC protein on the macrophage. Cytokines released by the TH cell stimulate it to proliferate. Then, the TH cell proliferates and forms a clone.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 46

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 47

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 48

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

April 5 Notes: The central role of helper T CD4 cells is to help activate nave B and CD8 cells. Cytotoxic T cells and B cells are nave when they are first made, until they are activated by the cells of the innate immune system. Inactive CD8s do not secrete cytotoxic molecules. Nave CD4 cells dont make the cytotoxic T-activating cytokines that they secrete in their active state. Nave B cells do not secrete antibodies in their inactive state they contain antibodies on their surface, but dont secrete them. All lymphocytes must be activated before they can start doing their jobs. Only cells that have the ability to bind the pathogen through their antigen-specific receptor will be activated. B and T cells have antigen receptors of only a single specificity. Many of these are on the surface, around 10000 of them, but there is only 1 binding specificity. First, a nave CD4 cell must itself get activated in the following process:

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 49

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

1. The antigen is taken up by phagocytosis and degraded in a lysosome. This breaks down the proteins of the microbe into its components, some of which will be used in signaling. 2. Interleukin-1, a cytokine, activates a helper T cell. These cytokines cause the CD4 cell to change its gene expression to start secreting its own cytokines. 3. A T cell receptor recognizes an antigenic fragment bound to an MHC 2 protein on the macrophage. This is an interlocking of a set of receptors, one on the antigen-presenting cell and one on the CD4 cell. The triple signals, the MHC 2 binding, additional interlocking receptors, and cytokines, are all required for activation as a safeguard against autoimmunity a nave cell that only receives one of the three signals will become anergic, unable to ever become activated, as an additional safeguard against mutation and disease. 4. Cytokines released by the CD4 helper T stimulate it through autocrine signaling to divide and form a clone. 5. The helper T CD4 cell proliferates and forms a clone, with activated effector cells and long-lived memory T cells. We become immune to things through immunological memory. When a CD4 T cell is activated and forms a clone, it forms two distinct populations of cells: 1. Activated CD4 T effector cells are short-lived, but highly active. They help eliminate the infection quickly once made. 2. Memory cells are not nearly as active. However, they are long-lived. Should the pathogen return after the first infection, it will be found more easily and a response produced more quickly because these memory cells circulate through the blood and lymph, producing activated T cells should they find the pathogen. Memory cells are

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 50

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

partway through activation. When they get activated, they expand and differentiate into more effector cells and more memory T cells. With more infections, there is an amplification of the number of effector cells because there are more memory cells to be activated and expand. Activation of a nave B cell:

1. The binding of an antigen to a specific IgM receptor triggers endocytosis, degradation, and display of the processed antigen. Once a CD4 cell has been activated, it can activate a nave B cell. This B cell will have bound the exogeneously-derived antigen, processed it, and presented it to the CD4 cell in an MHC 2 protein complex. 2. A T cell receptor recognizes an antigenic fragment bound to a MHC 2 protein on a B cell, and is activated. 3. Cytokines activate B cell proliferation, differentiate, and clonal expansion. 4. B cells proliferate and differentiate. Memory cells will store the information for later, while effector plasma cells are produced. 5. Plasma cells, effector B cells, produce antibodies. In humoral immunity, the binding of antibodies to antigens inactivates these antigens by:

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 51

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

1. Neutralization blocks viral binding sites, coats bacteria and/or opsonization. 2. Agglutination of antigen-bearing particles, such as microbes. 3. Precipitation of soluble antigens. These first three items enhance a macrophages ability to phagocytose and digest the pathogen. 4. Complement fixation, activation of complements such as the Membrane Attack Complex that punches a hole in the cell membrane that directly leads to cell lysis without the help of a macrophage. B-cell receptors, antibodies, have variable regions and constant regions. They have constant regions, which are constant between every antibody, and variable regions that are specific to the particular antigen. They are symmetrical, with two chains on one side that are identical to two more chains on the other side. Each side has a heavy chain, 440 amino acids long, that attaches to the plasma membrane of the B cell, and a light chain along the ends, connected by disulfide bridges, around 220 amino acids long. The overall shape of an antibody is a Y, with the two heavy chains with attached light chains bending and pointing away from each other. The antibody can bind the same shape of antigen twice since it contains two copies of the heavylight end variable chain. Clonal selection of B cells: the B cell that can bind the specific antigenic determinant will undergo proliferation and differentiation. Plasma cells can secrete 5000 antibodies per second. Thus, B cells are selected for proliferation by their ability to bind the

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 52

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

specific antigenic determinant. B activation gets activated by a helper T cell when it presents the digested foreign microbe to a helper T cell. Classes of antibodies:

1. IgG is a monomer, free in plasma about 80% of circulating antibodies, is the most abundant antibody in the primary and secondary responses. It crosses placenta and provides passive immunization to the fetus. 2. IgM is a pentamer, located on the surface of B cells and free in plasma. It is an antigen receptor on the B cell membrane, is the first class of antibodies released by B cells during the primary response. 3. IgD is a monomer, on the surface of B cells. It is a cell surface receptor of mature B cells, important in B cell activation.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 53

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

4. IgA is a dimer, found is plasma as a monomer and as a polymer in saliva, tears, milk, and other body secretions. It protects mucosal surfaces and prevents attachment of pathogens to epithelial cells. 5. IgE is a monomer, secreted by plasma cells in the skin and tissue lining gastrointestinal and respiratory tracts. It is found on mast cells and basophils, triggers release of histamine when bound to antigen. The histamine contributes to inflammation and some allergic responses. April 7 Notes: There are 5 types of antibodies, above at the end of last lecture. Cytokines determine which class of antibody is generated and secreted. In the B cell activation, if no cytokine is received, pentamer IgM is secreted. If Interleukin-4 is received, monomers IgG and IgE are secreted. If TGF- is received, IgG and dimer IgA is secreted. IgE secreted by a plasma cell binds to a high-affinity Fc receptor on a mast cel. When an antigen binds to IgE, the mast cell will be activated (and may engulf the antibody and attached antigen) and granules and histamine will be released. Because of immunological memory, in a second exposure to an antigen, the antibodies will be released much faster and many more of them will be made. The primary response of the specific immune system is slow to arise because the B and T cells have to first find the pathogen they are specific for, and get activated, differentiate and multiply. It can take as much as 14 days to get a high concentration of antibodies and effector T cells. A second reason is that we have many memory cells specific for a pathogen circulating in our bodies. The find the displayed pathogen faster and since they are already midway to activation, they get activated more quickly than a nave cell would. There are more of them, and they may all respond. As a result, our secondary responses to disease are both quicker and more robust. An overview of the immune response: An antigen, upon first exposure, is engulfed by a macrophage or other antigen-presenting cell. The macrophage stimulates a helper T cell, which does three purposes. It creates memory T cells. It also stimulates B cells, which give rise to memory B cells and plasma cells, which secrete antibodies. The helper T cell also stimulates cytotoxic T cells, which give rise to memory T cells and active cytotoxic T cells that respond to disease. Antigen-presenting cells also directly stimulate cytotoxic T cells, and antigens directly activate B cells. A second exposure to an antigen stimulates memory B cells and memory cytotoxic T cells, as well as memory helper T cells that stimulate memory Bs and memory Ts. HIV can infect cells that have CD4 receptors on their surfaces. Helper T cells and macrophages have CD4 on their surfaces, so HIV disables both the innate and adaptive immune system. HIV steals membrane from the host cells and uses it as its own phospholipid bilayer. On their membrane, they have two glycoproteins, gp120 and gp41. HIV has proteases to remove proteins, integrase, and reverse transcriptase to turn its RNA into DNA. (RNA is the genetic material of HIV.) Reverse transcriptase is rather error-prone, causing many non-functional proteins to be made. In infection, the outer gp120 (on the end of gp41) attaches to the CD4 receptor and its coreceptor. It then brings itself into the cell, turns its RNA into DNA, and inserts the DNA into the cell DNA. This DNA uses the cell machinery, replicating its own proteins and creating new viruses. In HIV infection, the T-cells are killed. After the T-cell concentration drops to nearly zero, the antibody concentration begins to drop, and the person will be killed by other infections.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 54

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 55

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

Chapter 42: The human heart and circulation: the metabolic needs of larger animals are met by a circulatory system that transports nutrients, respiratory gasesand metabolic wastes throughout the body. It includes the:

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 56

BIOL102 Notes Professor Adrienne Alaie


1. 2. 3. 4. 5. 6. 7. 8. Vena cava Aorta Lung Spleen Liver Kidney Intestine Colon.

Spring 2011

Without a circulatory system, a substance would need to diffuse through a vast distance, very slowly. Circulatory systems minimize the distance that nutrients must passively diffuse in order to enter or leave a cell. It brings the substance near the cell, and from there the substance may diffuse the short distance. By transporting fluids, the circulatory system functionally connects the body cells to the organs that exchange gases, absorb nutrients, and dispose of wastes. A circulatory system has three basic components: 1. A circulatory fluid 2. A set of interconnecting tubes 3. A muscular pump the heart, that puts the fluid under hydrostatic pressure, making it flow. In an open circulatory system, the circulatory system is continuous with hemolymph in the sinuses surrounding organs, which is drawn into the heart, where it is pumped into pipes that empty into a different part of the hemolymph. In our closed circulatory system, discontinuous with the intercellular spaces, blood is pumped from the heart to progressively thinner vessels, diffusion takes place in capillaries, that empty back into veins that take the blood back to the lungs and heart for reoxygenating and repumping. There are a few advantages to this: Fluid can flow more rapidly through vessels than through interstitial spaces so transport of nutrients and wastes to and from cells is much more rapid than in an open circulatory system. Closed circulatory systems can be selective in directing blood to specific tissues. Specialized cells and large molecules that aid in transport can be kept within the vessels but can drop their cargo to tissues where it is needed.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 57

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 58

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

The total length of blood vessels in an average human adult is more than twice Earths circumference, over 50000 miles. The heart (which wont be on this exam so Ill finish after this midterm) has been started today but continues in the next notes section. April 14 Notes: Parts of the heart:

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 59

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

1. 2. 3. 4.

The superior vena cava goes from the top of the heart to the head and upper limbs. The right semilunar valve covers the pulmonary trunk. The right pulmonary veins run from the lungs to the right atrium. The right AV valve, also known as the tricuspid valve, prevents backflow from the right ventricle back to the atrium. 5. Right ventricle weaker than 6. Muscles that prevent valve from everting 7. Inferior vena cava 8. Septum 9. Arch of aorta 10. Trunk of pulmonaryrteries 11. Left semilunar vlve 12. Left pulmonary veins 13. Left atrium 14. Left AV valve, also known as the bicuspid/mitral valve 15. Left Ventricle 16. Endothelium and underlying connective tissue 17. Inner layer of pericardium 18. Hearts apex 19. Myocardium The valves are used to prevent backflow so that blood moves in one direction. The two sides of the heart pump blood into different circuits: The right side pumps blood into the pulmonary

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 60

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

circuit (lungs) and the left side pumps it into the systemic circulation (rest of the body). The walls of the left ventricle are more muscular and put more force on the fluid in the left ventricle than the right ventricle puts on its fluid. This pressure allows for distribution throughout the body. Blood goes through both circuits at the same time because the ventricles contract in unison. The first branch off the aorta is the coronary arteries: 1. 2. 3. 4. 5. Aorta Right coronary artery Left anterior descending coronary artery Circumflex coronary artery Left main coronary artery

If an individual blood cell is traced, we will see: 1. Deoxygenated (only 75% of its oxygen capacity) blood returns from the body (through the inferior or superior vena cava) to the heart, entering the right atrium. 2. Blood enters the right ventricle through the open atriventricular valve (tricuspid valve). 3. Blood is pumped from the right ventricle to the lungs when the ventricle contracts. 4. In the lungs, gas exchange occurs, and the blood cell picks up an O2 molecule before returning via the pulmonary veins to the left atrium. 5. After it goes through the lungs (pulmonary circulation), oxygenated blood returns to the left atrium from the lungs. 6. Blood enters the left ventricle, through the open atriventricular valve (bicuspid valve). 7. When the ventricles contract, the oxygenated blood is pumped from the left ventricle to the body through the aortic arch into systemic circulation. Blood goes from the vena cava to the right atrium to the right ventricle to the pulmonary artery to the capillaries of the lungs where gas exchange occurs, to the pulmonary veins to the right atrium to the right ventricle to the aorta, through systemic circulation and the capillaries of other organs, where deoxygenated blood then goes back to the vena cava. The heart contracts through electric impulses, between 80 and 100 times per minute for humans. Control of heart rhythm:

1. Pacemaker generates wave of signals to contract. The SA node, also known as the pacemaker, has self-excitable cells, that excite with regularity. When excited, they release electrical signals. 2. Signals delayed at AV (atriventricular) node this way, the ventricles and atria dont contract at the same time, and the atria can finish contracting before the ventricles start. The cells of the AV node are also self-excitable, preventing ventricles and atria from contracting simultaneously. 3. Signals pass to heart apex once the AV node allows signal passage, the signals pass down the bundle branches to the heart apex.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 61

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

4. Signals spread throughout ventricles, the ventricles contract, and the signals are expelled. Ventricles contract approximately .2 seconds after the atria contract. Although the two sides of the heart have different circulations, electrical signals to contract must be able to reach both sides of the heart simultaneously. Cells of the heart are connected by intercalated discs, spotwelds that tether heart muscle cells together and contain gap junctions that allow ions to flow from one cell to another. The cells of the atria must be in electrical continuity, and the cells of the ventricles must be electrically continues but the atria and ventricles cannot contract simultaneously. The cardiac cycle is one complete sequence of pumping and filling, and takes only around .8 seconds. 1. Atrial and ventricular diastole half the time of the cycle, .4 seconds. The AV valves are open, the heart is relaxed, the semilunar valves are closed (preventing backflow), blood is flowing into the atria, and from the atria into the ventricles. The pressure in the aorta is low, as is the pressure in the left ventricle, but the volume of blood in the left ventricle increases as blood flows in. 2. Atrial systole, ventricular diastole .1 seconds out of the .8-second cycle, in which the atria contract to fully fill the ventricles. The atriventricular (tricuspid/bicuspid) valves are open, the semilunar valves are closed. Ventricular blood volume hits a peak as blood is forced into the ventricle. 3. Ventricular systole, atrial diastole - .3 seconds out of the .8-second cycle, in which the ventricles contract to send blood to the required destinations. The atria relax, but the AV valves are closed, while the semilunar valves are open to allow blood to leave the heart via the arteries. The aortal pressure hits a peak, as does the left ventricular pressure, as would be expected.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 62

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

Heart murmurs occur when the AV valves do not close completely. Even when the ventricles are diastolic, the aortal pressure does not decrease nearly as much as the ventricular pressure does. The reason for this is that the arterial walls are much thicker than those of the veins. The arterial walls compress the blood. The artery walls are made of (from inside to out) endothelium, basement membrane, elastic tissue, smooth muscle rings, elastic tissue, and an outer coat. The elastic tissue absorbs some of the pressure of the pumping from the ventricle, and then transmits it back to the blood as the pumping pressure relaxes. This allows for a fairly constant blood pressure over time, allowing body process to continue at the same rate regardless of point of time in the cardiac cycle. The total cross-sectional area of the various blood vessels differ as does the thickness of their walls. Arteries have the thickest walls, made up of the thickest layers, and capillaries have the thinnest walls for substance exchange between the circulatory and interstitial fluids. Capillaries have only an endothelium and basement membrane. Veins are the most variable in shape, with an endothelium, basement membrane, smooth muscle, elastic fibers (but not as much as in arteries) and an outer coat. Blood is not pumped from the veins to the heart; it comes in on its own as the body moves.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 63

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

Capillaries come in different varieties that differ in their permeability: 1. Continuous capillary the brain has continuous capillaries. This is the most restrictive, where the gaps between the cells of the capillary are most stitched, with no space between, requiring that the substance go through the two plasma membranes of the capillary cell. The blood-brain barrier must be selected for, with tight junctions. There are glial cells in the brain to pick up anything unwanted that might possibly leak through the capillary. 2. Fenestrated capillary the kidney has fenestrated capillaries. Fenestrated capillaries are less restrictive, with pores that allow limited passage between blood and pericapillary space. 3. Sinusoidal capillary the liver has sinusoidal capillaries. Sinusoidal capillaries are the least restrictive, with large paracellular gaps that allow large amounts of substance to flow from the blood. These are wide meandering fenestrated capillaries in the liver, ant pit, and bones, allowing white blood cells to enter and exit along with other larger substances. Most substances can travel through simple, passive diffusion. Blood moves through the arteriole system through arteries, arterioles, and the arterial end of capillaries under the pressure put on it from the pumping of the heart (hydrostatic pressure). Blood closest to the heart will move the fastest. Blood moves slowest in capillaries, where total surface area is

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 64

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

highest. There is very little pressure in veins, even though the cross-sectional area drops and the blood velocity increases a bit, because fluid is lost to the tissue at the site of exchange. Pressure is too low to truly return blood to the heart; blood returns with body motion and skeletal muscle contraction on veins, with help from valves, and change in pressure due to breathing. The next 3 lectures are taught by Dr Persell. He reportedly has a tendency to require us to know stories that he tells in class. So pardon the inclusion of what we Alaie students regard to be stupid, if amusing, stories this guy requires us to know them!

April 28 Notes: Biological change has several meanings. Definitions: 1. Development change of an individual organism in one lifetime. 2. Evolution change on a population or species over many generations. Voluminous, ongoing observations demonstrated early on that evolutionary change is a fact. They still do. To explain the facts of evolution, Charles Darwin proposed several brilliant theories: 1. Populations adapt over generations through natural selection. 2. As populations adapt to changing environments, they evolve different adaptations. They descend from ancestor species and diverge into different related species, showing new modifications that reflect their adaptation to new and different environment. 3. For sexually reproducing organisms, adaptations often include traits that increase mating success through sexual selection.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 65

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

4. Humans and human behavior have evolved under the same biological laws that govern natural selection in all other organisms. 5. No other theory comes even close to explaining all the observed facts. The facts of evolution: Organism populations species change over time. The fossil record continues to provide evidence for this change. All lines of evidence biochemical, geological, ecological, behavioral, etc are consistent with this view. A theory helps explain and understand the facts. A theory also has predictive power. The theory that explains the facts of evolution has several components. The cornerstone is The Theory of Natural Selection, proposed jointly by Charles Darwin and Alfred Russel Wallace in 1859. Darwin has deservedly earned most credit for this because: a) Wallace remained mystical and believed that humans were somehow not under the influence of natural selection. b) Darwin had written about it first c) Darwin went on to elaborate upon his theory. Evolution is defined as the change in a hereditary gene pool of a population over generations. Individuals develop populations evolve, not individuals. Evolution is often divided into microevolution in the short term (e.g. change in skin color over the course of a few generations), and macroevolution in the long term (e.g. emergence of modern dogs from gray wolf populations some 20,000-20,000 years ago but not yet fully diverged as a new species). Speciation requires reproductive isolation. With isolations, gene pool (populations) evolve separately (microevolution) and diverge further. Without isolation, gene pools may intermix so that the population remains one potentially interbreeding species. Nothing makes sense in modern biology and medicine except in the light of Darwinian evolution. Evolutionary thinking is consistent with virtually every other study of human activity. Current research in evolution revolves around biochemistry, molecular genetics, and developmental biology, but also heavily influences the humanities. Fossil records are voluminous facts that require theoretical explanation. A theory organizes existing facts to make sense and allows predictions about future to-be-discovered facts. Using his own theory, Darwin predicted the necessity of finding a dinosaur fossil that had feathers one was found during Darwins life. Fish with wrist bones have been found more recently as well. Vestigial remnants of human bones are still found in several species of living whales today. 3 different bones from three very varied species can be quite similar although humans dont have true visual tails, we have a notochord just as the other animals. Many of Darwins theories came from observations of animal adaptations found in the Galapagos Islands. Darwin viewed the history of life as a tree, with multiple branching from a common trunk out to the tips of the youngest twigs, representing the diversity of organisms living in the present. Evolution requires the integration of observed facts into scientific theory. According to earlier fossil records, Ardipithecus Ramidus fossils are not a transition between later hominins and a common ancestor that supposedly looked like chimpanzees now alive. Some features tie these fossils to all later hominins, including the younger (3.2 million-year-old) Lucy. Ardipithecus walked upright but not as well as Lucy or later hominins. As with all fossils, Ardipithecus provokes questions about and redefinition of what it means to be a member of the human family. Continuing to look at newly-recovered fossil

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 66

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

record reveals that earlier hypotheses about common ancestors with chips are incorrect, as Ardipithecus limbs are more like monkeys than like apes, rejecting the hypothesis that our ancestors were more like chimps. In other words, modern chimps also have evolved from our common ancestor. Bipeds evolved by upper pelvis modification. A lack of strongly projecting canine teeth (like chimps) suggests reduced male-male conflict, greater pair bonding, and more male parental investment. The newer explanations state that gorillas and panins (chimps) were a side branch, and humans are in fact descendants of Ardipithecus. We must understand from this the general idea that different species may be side branches, or may be part of the modern human line. Much of evolution is not truly known because of notextensive-enough fossil records. It is possible that we are the direct descendants of one species; it is also possible that we are descended from interbreeding between two different species. Dates to know in the concept of a changing Earth: 1. 1504 Leonardo da Vinci calculated 200,000 years for Po River rocks to form from water erosion. 2. 1650 Reverend James Ussher calculated the origin of the Earth at 4004 BC, using Christian scripture as his evidence. 3. 1795 James Hutton proposed that the earth needs to be tens of millions of years old to explain geological structures. 4. Early 1800s Charles Lyell refined those ideas (uniform change). 5. 1862 Lord Kelvin asserted that Darwin had to be wrong in his claims of an Earth at least 300 million years old. Kelvin rigorously calculated the suns age at only 30 million years based on its size and heat loss. He argued that there was only a finite amount of heat that could have been created. 6. 1907 radioactivity was established, and Kelvins heat arguments against Darwin were shown to be wrong. Estimates now are around 4.2 billion years for Earths age. The concept of species change: Lamarck proposed complex organisms evolved from preexisting simpler ones in 1809, the year of Darwins (and Lincolns) birth. Darwin and Wallace each saw enormous biological variation and settled on explaining evolution by the Theoryof Natural Selection. Almost all cultures are steeped in a notion of organisms being fixed. Even reincarnations consider each incarnation fixed. Genetic variation involves allelic diversity, diversity in the different genes expressed in a particular allele. Mouse expression of the Agouti gene delays differentiation of ventral melanocytes in beach species, causing lighter color and microevolutionary divergence. There is a general scheme of divergence (descent with modification) from a common ancestor. Each color represents separately reproducing organisms (a species). Some show greater similarity to each other than others do. There is divergence over the course of the history of an organisms ancestors, when isolation occurs and microevolution may allow for natural selection in a given path over the course of history in a given population. 45% of plant loci have more than 1 allele in their gene pool (heterozygosity). There is more than 15% heterozygosity in plants and birds. Insects are very heterozygous, with more than 50% heterozygosity. Mammals are more that 20% heterozygous, including humans leading to enormous variation. Every human individual is genetically unique except for identical twins who are copies of the same gene pool. So, a population has a pool of different genes

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 67

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

(gene pool) that intermix during sexual reproduction, and most genes show variations (alleles). The gene pool is the sum of all alleles in a population. Allele frequency is the frequency of a given gene at an allele. May 3 Notes: A population that has a pool of different genes (gene pool) that intermix during sexual reproduction, and most genes show variations (alleles). The gene pool is the sum of all alleles in a population. At the locus, X, allele frequency is .2 for X1, .5 for X2, and .3 for X3. Creating a model for genetic variation (Hardy and Weinberg): This model is under the following assumptions: First, assume the absence of evolution. Assume all variations never change the gene pool does not vary over time (ignoring evolution and mutation, in a complete genetic equilibrium). The model was introduced by Reginald Punnett, the developer of the Punnett square, who played cricket with mathematician G.H. Hardy.

Assuming no evolution means: 1. Mutations do not occur. 2. Natural selection does not occur. 3. Population is extremely large.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 68

BIOL102 Notes Professor Adrienne Alaie


4. All members interbreed randomly. 5. No migration into or out of population.

Spring 2011

The Hardy-Weinberg Equation: First assume minimal variation only 2 different alleles for a gene, found in a population at a frequency of P and Q. AA are homozygous dominants. Aa is heterozygous. And aa are homozygous recessives. P is the frequency of the dominant allele, AA + Aa. Q is the frequency of the recessive allele, aa + Aa. There are only two alleles, so P + Q = 1. Haploid frequencies are P = 1 Q, and Q = 1 P. Diploid frequencies are (P + Q)2 = 1. Diploid genotype frequencies are P2 + 2PQ + Q2 = 1. An example, with a given population with 45% homozygous dominant, 20% heterozygous, and 35% homozygous recessive, the frequency of alleles in the population (45% + *20% = 55% dominant allele, 35% + *20% = 45% recessive allele) reflects on the Punnett square, according to the equation P2 + 2PQ + Q2 = 1. P2 is the frequency of homozygous dominant AA individuals. Q2 is the frequency of homozygous

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 69

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

recessive aa individuals. 2PQ is the frequency of heterozygous Aa. Without evolution, frequency remains constant. But after several generations, there is change, proving that evolution does exist. Another example: albinism is a homozygous recessive trait in many mammals. The average frequency is 1/20000, which is Q2. Q is the square root of that, .007. P = 1 Q, gives a .993 dominant alleles frequency. 2PQ, .014 is the heterozygote frequency (carriers) 98.6% are homozygous dominant, and around 1% are carriers. (Story that Persell mentioned: A reminder of Darwins Dangerous Idea: Tanzanian witchdoctors have been implicated in the murder of albinos, whose body parts are said to bring good luck and wealth. The Tanzanian president said that 19 have been killed recently. Persell wishes us to learn that Biologists came up with the idea of diversity FIRST! ) Anyway, over several generations the Hardy-Weinberg assumptions are FALSE for several reasons: 1. Mutations do occur 1/10,000-1/1,000,000 for human genes. Most human sex cells contain at least one gene mutation. For at least 100 million sperm per ejaculate, thats a lot of mutations. HIV mutation rate is approximately 1 mutation every 3 rounds of replication. For 1-10 billion virions per day, that equals around 300 million mutations per day. HIV evolves within each host. HIV evolution has led to 3 large viral families: HIV1, HIV-2, and SIV. 2. Non-random mating assortative mating (non-random) is typical, either positive or negative typical of all animals (including humans) and plants. Example here is identified by Darwin (the primrose). On average, humans select mates with a height difference of +-5 inches, with males generally taller. Notice on average. Female crickets preferentially mate with males that make more robust sounds. MHC (Major Histocompatibility Complex) proteins are reportedly also implicated in mate selection. Discrimination based on dissimilar MHC proteins has been demonstrated in mice, rats, lizards, and fish. May optimize the number of different alleles in the offspring and prevent inbreeding. A 2008 study on European-American couples demonstrated MHCdissimilar mate selection in humans, supporting the hypothesis that MHC influences mate choice, at least in some populations. Hypothesis: choosing mates with dissimilar MHC genes generates significant heterozygosity at MHC loci and significantly greater resistance to pathogens. Forwarded as one hypothesis to explain commonly found incest taboo. And here Dr Persell talked a lot about what exactly the incest taboo is, although personally I think it doesnt need explaining we dont marry our siblings possibly because heterozygous MHCs are beneficial. Non-random mating leads to sexual selection, proposed by Darwin to explain sexual dimorphisms that have no obvious adaptive value for the individual (no obvious benefit for survival). Example: larger male size in most (but not all) mammals, peacocks tail, male robins red feathers, human female pendular breasts. An experiment shows that sexual selection is responsible for the evolution of long tails in African long-tailed widowbirds. Males were captured and their tails artificially lengthened or shortened by cutting or gluing on feathers, then released and their reproductive success measured by counting the number of nests in each males territory. The artificially-lengthened tailed birds mated twice as often than did those with normal-length tails, while those with cut tails mated the least of all. But the hypothesis is not that the long tail is actually

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 70

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

beneficial for the bird it is simply seen by the opposite sex as an omen of good genes, even though it is not always the case. Sexual selection and male-male competition is very complex. One example: Male Atlantic molly fish, when alone, choose the most desirable female (usually the largest with the brightest color). When other males are around, however, the first male immediately chooses a less desirable female (smaller with duller color). Other males then copy the first male. The original male then returns, after deceiving the male competitors, to mate with the more desirable female fish. This raises the possibility of diverging species over 70000 years. The Atlantic molly (ocean) and Amazonian molly (river) look very different. Males tend to choose their own species over a related asexual species, but when a second male is put in the tank, the first male may go for the other, deceiving the competitor male. When the other males follow, interacting with Amazon mollies, which rely on insemination from male Atlantic mollies to trigger parthenogenesis, female-only embryogenesis (no gene flow between the two species). The original male uses deception, which is employed by closely related parthenogenic species, while the original male returns to its own species. Parthogenetic animal eggs and semen do not fuse just membrane contact from insemination causes the egg to reproduce.

3. Genetic drift migrations, founder effect. Significant changes in allele frequency may be affected by chance in small populations. Random movements of small groups that then become isolated, reproduce and lead to a larger population with unique traits. The blue people of Appalachia are an example, an 18th-century immigration of a small population with an enzyme deficiency inefficient oxygen binding leads to less red in capillaries, which then appear blue. The result today is a high percentage of people with methemoglobinia iron and cyanosis. Persell also told the story of how there are whiteskinned people on Tahiti, the descendants of British mutinous sailors. This is an example

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 71

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

of microevolution. Genetic drift leads to evolution but does not always directly lead to successful adaptations.

4. Natural selection the explanation for adaptive evolution. Natural selection and evolution are not identical. Natural selection is an explanation for adaptive evolution, not random and small evolutionary changes. Some variants in a population leave more offspring than others do. Other variants dont reproduce at all. Over time, the frequency of the most fertile types that survive will increase. Their reproductive fitness is greater. But just because a type is chosen by mates, or wins male-male competition, doesnt mean that the type is better although giraffe long necks help in mating, they also leave them vulnerable to attack by predators. From generation to generation, their increased reproduction changes the gene pool (genotype) and the observed traits (phenotype): adaptive evolution. This differential reproduction depends on successful survival of those pre-existing types in a given environment: natural selection. Sexual selection is a form of natural selection, increasing reproductive success because of traits that may have nothing to do with individual survival. For example, elks have long horns to attract mates and fight other males, but these horns may cause elks to get stuck in trees.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 72

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

Differential Predation in Guppy Populations Researchers have observed natural selection


Leading to adaptive evolution in guppy populations
Reznick and Endler transplanted guppies from pike-cichlid pools to killifish pools EXPERIMENT and measured the average age and size of guppies at maturity over an 11-year period (30 to 60 generations). Pools with killifish, but not guppies prior to transplant Experimental transplant of guppies

Predator: Killifish; preys mainly on small guppies


Guppies: Larger at sexual maturity than those in pike-cichlid pools

Predator: Pike-cichlid; preys mainly on large guppies Guppies: Smaller at sexual maturity than those in killifish pools

Figure 22.12
Copyright 2005 Pearson Education, Inc. publishing as Benjamin Cummings

RESULTS After 11 years, the average size and age at maturity of guppies in the transplanted populations increased compared to those of guppies in control populations.

185.6 161.5 48.5 67.5 76.1 58.2

85.7 92.3

Control Population: Guppies from pools with pike-cichlids as predators Experimental Population: Guppies transplanted to pools with killifish as predators

Males

Females

Males

Females

CONCLUSION Reznick and Endler concluded that the change in predator resulted in different variations in the population (larger size and faster maturation) being favored. Over a relatively short time, this altered selection pressure resulted in an observable evolutionary change in the experimental population.

Copyright 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Canine evolution: dogs evolved from relatively tame wolves (i.e. early dogs) that followed human migrations for food. Early dogs in the Middle East picked up Asian wolf genes after human-dog migrations to Asia. Dog behavior, e.g. herding, shows similar genetic patterns, irrespective of where the herding dogs were bred. Signature of behavioral evolution: dogs have human homologue implicated, required for synapse stability in brain. Mutated form causes

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 73

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

Williams syndrome and leads to exceptional gregariousness, showing a correlation between social behavior and genetics. So everything from sight hounds to terriers to coyotes evolved from a common ancestor, Tomarctus (26 million years ago). But different ones evolved at different times. Although the original wolves might eat sheep, herding dogs will herd sheep. Small terriers will hardly do anything other than bark annoyingly at the sheep. Dog breeding is artificial selection. For Whippets very fast dogs, heterozygosity for the myostatin mutation results in fast whippets. Homozygosity for myostatin mutation results in overmuscled bullies. Humans control this process by killing (euthanizing is the politically correct term) the bullies and normal dogs, leaving the heterozygous fast whippets to be sold. This is an example of artificial selection, where evolution is not allowed to run its course. Canine evolution is a combination of artificial and natural selection. The Tomarctus, through natural selection, evolved to become the Gray Wolf. When they mated, they produced a wide variety of new breeds that were then artificially selected by humans for reproduction.

Artificial Selection In the process of artificial selection


Humans have modified other species over many generations by selecting and breeding individuals that possess desired traits
Terminal bud Cabbage Lateral buds Brussels sprouts

Flower cluster

Leaves

Cauliflower

Kale

Flower and stems Broccoli Wild mustard

Stem Kohlrabi

Figure 22.10
Copyright 2005 Pearson Education, Inc. publishing as Benjamin Cummings

May 5 Notes: Laboratory artificial selection: in a lab, microevolution is easy to demonstrate. It is possible to select, for instance, flies with only short bristle length. Evolution in nature: Darwins finches and natural selection. The ancestral form of the finch is the blue-black grassquit. Finch evolution displays both the founder effect and genetic drift. The founder effect, as stated last time, is a small pool of alleles isolated from the original population. Genetic drift involves random shifts in a small gene pool. Evolution happens even now. The large cactus finch is intermediate in beak form and body between the large ground finch and cactus finch where both are absent (on Espanola) but more like the cactus finch where large ground finch is present (on Genovesa). It indicates the natural

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 74

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

selection of competitive morphologies. The number of actual finch species, as many as 14, is in dispute because speciation is ongoing right now and hybridization occasionally occurs. It reflects 30 years of study by Peter and Rosemary Grant. And no, we dont care about his stupid book! (He has allowed me to make fun of him in my notes, so I will make a point of mentioning that he went off on a tangent about U Montana students not liking to read about evolution). Microevolution leads to small changes which are magnified when populations undergo speciation because of factors such as geographical isolation and changes in reproductive physiology, including sexual selection (swordtail fish). Nodes occur in evolutionary branches as periods in time when speciation begins to occur. Hybridizing species can be explained by the fact that theyre closely related species now undergoing speciation in diverging from a common ancestor. Hybrids signify gene flow between 2 closely related species, but the offspring are not fertile. Although lions and domestic cats cannot interbreed, more recently diverged species (e.g. lions and tigers) can and do interbreed, but more distantly related species cannot interbreed. A sample Hardy-Weinberg problem: 250 loci have AA, bb, CC, etc, 250 different fixed alleles, while 250 loci have Dd, Ed, Ff, etc, 200 total different alleles. There are 750 different alleles total. Multiple loci are multiple genes at a particular location on the genome. P2 + 2pq are the H-W terms that indicate the frequency of those with at least one A allele (some have 2). 120 people in population 16 AA, 92 Aa, and 12 aa. If using the HardyWeinberg equation reveals something different than expected, then the population is evolving. The definition of speciation: Folk concept all societies give groups names like dogs, cats, humans, flowers, and fish. Dogs beget dogs, fish beget fish, and people beget people. Biological species concept: a reproductive community of populations (reproductively isolated from each other) that occupies a specific niche in nature. Challenges to this: this is not always testable (there are 16000 lakes in Wisconsin, each with bluegill sunfish it is not known whether species of two given lakes are separate species or the same one.) Other concepts: 1. Phenetic smallest groups consistently distinct and distinguishable by ordinary means, mostly morphological. If it looks like a duck, then it probably is one. 2. Phylogenetic smallest group that possesses at least one diagnostic character fixed in reproductive units i.e. ability to do photosynthesis. May not look alike. At branching points, during the evolution of new species (red wolves, gray wolves or Cro Magnon and Neanderthal) the concept of species does not completely work, since population changes are dynamic and occurring over time. Branch points are periods of divergence and can last thousands of years, as with dogs and wolves. Isolating mechanisms for BSC (Biological Species Concept): 1. Premating a) Ecological different habitats. b) Temporal different breeding times. c) Behavioral different mating recognition. d) Mechanical different reproductive organs. Example: in Mallard ducks, if males have a long phallus, females have intricate genital tracts. Tremendous variety in anatomy that contributes to speciation. Also contributes to battles between sexes

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 75

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

within a species, as females dont like having a twisted Mallard penis stuck in their convoluted female urogenital tract. 2. Postmating a) No gamete fusion. b) Hybrids dont develop normally. c) Hybrids develop but are sterile. d) Hybrids can even reproduce but seldom survive, showing poor fitness. Imprinting and sex competition: Imprinting is differences in genetic outcome from same genes delivered by male compared to delivered by female. These traits are monoallelic. A mule is an interbreed of a male donkey, female horse, while a hinny is from a male horse, female donkey. Male imprinting drives larger placenta and fetal growth. Female imprinting inhibits larger placenta and fetal growth (hinnies are smaller than mules). These genes are, perhaps, rather selfish (or so Persells slide says). Sexual reproduction is a balance between male and female genetic interests. Examples of premating and postmating interbreeding problems: Darwins finches females wont choose mates with beaks as large as those of a closely related species. Drosophila melnogaster mate with Drosophila simulans, but the male hybrids are sterile one gene is responsible, the nuclear pore gene. Mechanisms of speciation: 1. Allopatric geographic isolation. 2. Parapatric adjacent with some gene flow. 3. Sympatric speciation within a panmictic (interbreeding) population. Changes may be during early development. The embryos of alligator, human, and bird are very hard to differentiate at the embryonic stage. But with small microevolutionary changes during early development comes larger macroevolutionary changes. Development of skulls often differs. There is a strong similarity in early development of chips and humans. Differences appear later. Allelic changes may affect development of related organisms, leading to new species. Natural selection is the only mechanism of adaptive evolution. Successfully phenotypes exhibit structures and physiology that are adapted to ther environment they work. In turbulent water, the limpet (a type of mollusk) form is conical. Limpet species found in non-turbulent water have less conical shapes. Some mammalian adaptations: binocular vision and social perception. Natural selection: certain variations will not reproduce successfully. Their traits are inadequate as adaptations. They may be susceptible to predation, disease, climate change, and genetics. Alleles for those traits may decrease in frequency. Evolution is not passive organisms can change their own environment or migrate to new environments or interact. Patterns of natural selection:

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 76

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

The three modes of selection


Original population

Original population

Evolved population

Phenotypes (fur color)

Fig 23.12 AC

(b) Disruptive selection favors variants (a) Directional selection shifts the overall (c) Stabilizing selection removes at both ends of the distribution. These makeup of the population by favoring extreme variants from the population mice have colonized a patchy habitat variants at one extreme of the and preserves intermediate types. If made up of light and dark rocks, with the distribution. In this case, darker mice are the environment consists of rocks of result that mice of an intermediate color are an intermediate color, both light and favored because they live among dark at a disadvantage. rocks and a darker fur color conceals them dark mice will be selected against. from predators.

Copyright 2005 Pearson Education, Inc. publishing as Benjamin Cummings

1. Stabilizing birth weight, 5 digits, clutch size in birds 2. Directional bacterial resistance to antibiotics, early hominid cranium but there can be competing and opposite evolutionary pressures. 3. Disruptive sexual dimorphism, stable polymorphisms (white/brown hares), may lead to sympatric speciation. The extreme sexual dimorphisms may survive better than the means. Sexual selection, disruptive evolution, and sympatric speciation: in a fish species, there are open stream fish, with long spindle-shaped bodies suited for fast-moving water, and lozengeshaped fish suited for still water. The intermediate shape does not survive as well in either water. Stabilizing selection and humans very large brain: as birth weight goes up, the maternal mortality rate goes up, while the infant mortality rate goes up at low birth weights. Homologies: cats and humans have very similar limbs to humans. Structures morphological and molecular that have common ancestors but have since diverged. Mechanisms of divergence are genetic. Some homologous structures are Vestigial, lacking function the population has evolved from needing it, but the vestigial structure remains. During evolution, there are missing links that should be in the node between different families of species. Tiktaalik was a fish with limbs, showing evolution from fish to land animals. Genetics of evolution: a specific gene involved with limb development (in blue) reveals different levels of activity in mice and bats. Bat DNA placed in mice results in significant elongation in mice forearms, as with bats. Genetic polymorphisms, disruptive evolution: a sucker fish, Perissodus, is found in 2 forms, which remain stable in the population because slight deviances can stop the proper function of the fish. Several evolutionary solutions to the same environment problem bottom dwelling in marine environments. One species lies flat to avoid predation, while the other shrinks up under

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 77

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

perhaps a shell. When Darwin visited Australia, hed been in divinity school 3 years earlier writing in his diary that it looked as if God had designed everything twice, with the marsupial mole like the regular mole, and the marsupial mouse like the mouse weve been seeing around the classroom tonight. Although the wolf and Tasmanian wolf are very different, they have many similarities in the way they function. Convergent evolution is the selection of similar phenotypes by similar environments. The evolutionary history of horses: earliest horse fossils were dog-sized, developing to the size that they are now. Macroevolution of species involves a tree with many branches for instance, horses were extinct in North America for 10000 years before being reintroduced by humans. Biochemical evidence: amino acid sequences fill in the gaps in the fossil record, giving solid evidence behind evolution. The partial sequence of mitochondrial Cytochrome C human and chimp sequences are identical. The plants have different ones from humans, and mutations over the many years have caused divergence. Hemoglobin divergence: the divergence between humans and a species of monkeys must not have been much longer than 8 million years ago, while the divergence from dogs was longer ago. BMP4 protein expression controls jaw morphology, and the insertion of such a protein into developing species that would not normally have tooth buds can cause them to develop in chickens, although this does not work in more divergent preying mantises. Expression of both Bone Marrow Protein 4 (BMP4) and calmodulin genes affect Darwin finch beak development. The ancestor warbler had relatively low BMP4 and calmodulin protein concentrations, with a thin beak. On Galapagos islands, these differences are widely seen, as ones with thicker beaks have more BMP4 for more bone marrow protein development. In 1998 researchers identified a diffuse human condition (the KE family) whose symptoms include grammar and speech production (chromosome 7). A mutation, arginine to histidine, causes breakage. FoxP2 gene affects vocalization in mammals. In the 6 million years since the chimp-human divergence, there have been 2 mutations in the human FoxP2 gene, estimated to occur about 50,000 years ago. It is possibly critical for the evolution of human speech, socialization, and cognition. Intriguingly, the timing correlates with the explosion of early human culture. This completes our evolution lectures, and luckily we wont have to deal with Persell any more for the rest of this semester.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 78

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

May 10 Notes: The interrelationship of blood flow velocity, cross-sectional area of blood vessels, and blood pressure: blood travels 500 times slower in capillaries than it does in the aorta, .1 cm/sec versus 48 cm/sec. The surface area of the capillaries is much larger, so the blood travels slower. The pressure decreases through the arterioles and capillaries. The pressure is highest in the arteries because these vessels are leaving the pump that is the heart, while the blood in the veins is free to just flow. But the pressure in the aorta is not a high constant it goes up and down, between the highs of systolic pressure to the lows of diastolic pressure. However, in the veins, there is no pressure left. Walking and breathing brings the blood in the veins upward bit by bit against gravity, with valves closing in the wake of the blood. The heart, brain, and kidneys attempt to maintain a constant supply of blood. At any given time, blood flows through 25% of a capillary bed. Blood flow in capillary beds is controlled by precapillary sphincters. Most of the blood goes through the thoroughfare channel straight into the venules. When the sphincters are relaxed, blood is free to flow throughout the capillary beds. When the sphincters are constricted, blood only flows through the throroughfare channel. Some organs, such as the heart, brain, and kidneys, need a constant supply of blood while the skin might not.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 79

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

We now look at how the pressure drops off from the arterioles to the venules. The movement of fluid between capillaries and the interstitial fluid is a balance of opposing forces. The capillarys endothelium is only a single cell thick. 32 mm Hg blood pressure is opposed by 22 mm Hg osmotic pressure, with a net pressure of 10 mm Hg out as the fluid comes in. There is a high pressure put on it because of the heart at the arterial end of the capillary. But there is an inward osmotic pressure toward the plasma proteins and other particles that remain in the capillary. The net pressure out is 10 mm Hg, liquid that leaves the capillary bed. The blood pressure on the venous side is only 15 mm Hg, opposed by the same 22 mm Hg, makes a net pressure of -7 mm Hg inward, so much of the liquid that originally left the capillary bed on the arteriole end returns to the capillary bed on the venous end. The venous end is connected to the venules, which are connected to the veins, where blood is shunted through normal movements and closings of valves back up to the heart. Hydrostatic pressure is a pressure exerted by a liquid in response to an applied force it pushes outward, while the osmotic pressure of the blood pushes inward. Due to the loss of liquid due to the net pressure out on the arterial side, the hydrostatic pressure drops off, allowing the liquid to return on the venous side. The relationship of lymphatic and blood capillaries: The lymphatic system brings the released blood fluid with ions back to the blood. Lymphatic capillaries merge into larger vessels and ultimately into two lymphatic vessels: thoracic ducts that empty into large veins in the base of the neck. Parasites can block lymphatic vessels and cause a massive regional edema known as elephantiasis. The lymphatic system is useful for not only ferrying around lymphocytes, but

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 80

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

also for bringing the leftover blood fluid back to the blood. The lymphatic capillaries are in close association with the blood vessel capillaries and they serve to absorb the excess interstitial fluid released from the arterial end of the capillaries. The lymphatics eventually empty their fluid into two large veins that deliver it to the heart. The composition of the blood: Component: Water Salts Plasma proteins albumin and globulins. Function: Solvent Osmotic balance, pH Osmotic balance, pH buffering, regulation buffering, clotting, of membrane immune response. potentials.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 81

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

The atmosphere is made up of 78.89% nitrogen, 20.95% oxygen, a variable concentration of approximately .93% water, and .03% carbon dioxide. Air pressure is measured in millimeters mercury, in a barometer. In a barometer, the atmosphere is permitted to press down on mercury so that it flees into a vacuum tube it will flee to a height above the liquid of 760 millimeters at sea level. Each gas exerts a partial amount of this pressure. All these gases together exert this 760 mm Hg pressure at sea level, the sum of the partial pressure of all gases in the atmosphere. The partial pressure of oxygen is approximately 160 mm Hg. The partial pressure of carbon dioxide is approximately .23 mm Hg. Gas exchange can only occur in an efficient manner in our bodies because our circulatory system ensures that our cells are in effect close to a respiratory surface. We dont keep our respiratory surface on the outside, instead keeping it in an internal cavity, with the circulatory system bringing gases from our respiratory system to the rest of our cells. Lungs are tucked into our bodies to ensure that we

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 82

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

do not lose too much moisture to the atmosphere. Air is a much better respiratory medium than water is. The oxygen content of air is much higher than the oxygen content of water. The maximum oxygen content in air is 200 mL of oxygen per liter. The maximum oxygen content in water is only 10 mL per liter. Oxygen diffuses 8000 times more rapidly in air than in water. Water is 800 times more dense and 50 times more viscous than air so more energy is required to move water over the respiratory surface. Water breathing animals cannot survive outside of water because their respiratory surfaces collapse. But in water, they give themselves large surface areas in order to obtain the required oxygen. When the water is flowing the same direction as the blood is, diffusion can occur until the blood reaches equilibrium with the water. However, when blood flow is running counter current, then the water at any given point will always have more oxygen than the blood does, with the part of water having 99% oxygen favoring diffusion into the part of the blood with 90% oxygen, and the part of water having 15% oxygen favoring diffusion into the part of the blood with 10% oxygen. Fish employ counter current exchange whereby the blood just arriving to the ventilation surface from the tissues (containing the least amount of oxygen) meets up with water also containing the least amount of oxygen. As long as the water contains a greater percentage of oxygen than does the portion of the blood with which it comes in contact, oxygen will be delivered from the water to the bloodstream. This allows between 80% and 90% of all of the oxygen in the water to be delivered to the blood of the fish. This whole system is called counter-current exchange. An overview of animal gas exchange: the circulatory system brings blood to the internal side of the respiratory surface. Oxygen is given to the red blood cells in the blood stream, which brings it to the body cells, which release carbon dioxide, which is brought by the blood back to the respiratory surface. The circulatory stem links the cells to the respiratory surfaces. In many animal, the bulk of the bodys cells lack immediate access to the environment. The respiratory surface in these animals is a thin, moist epithelium. Partial pressures are important in determining movement of oxygen and carbon dioxide. The cells of the body use oxygen and release carbon dioxide, so the partial pressure of oxygen is low and the partial pressure of carbon dioxide is high. Oxygen moves through diffusion from the atmosphere to the circulatory system to the cells. Carbon dioxide moves through diffusion from the cells to the circulatory system to the atmosphere. Inhalation and exhalation are performed by the diaphragm. In inhalation, muscles contract, volume increases, pressure inside the thoracic cavity falls, the ribcage expands as do the lungs, and air flows in. In exhalation, muscles relax, volume decreases, pressure inside rises, the ribcage contracts, the lungs compress, and air moves out. In inhalation, the diaphragm contracts and moves down. The external intercostal muscles (between the ribs) contract and lift.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 83

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

May 12 Notes: The rate of diffusion is kA(P2 P1)/D, where k is the diffusion constant, A is the area for gas exchange, (P2 P1) is the difference in partial pressure of the gas on either side of the barrier to diffusion, and D is the distance across which the diffusion must occur (thickness of the barrier to diffusion). The k, diffusion constant which depends on the solubility o the gas and the temperature, is largely constant. The respiratory surface in the lung: there are 300 million alveoli, or air sacs, through which respiration occurs, providing a large surface area. The wall of the alveoli is fused with the capillary wall, giving a very small thickness, 1/200 th of the thickness of a book page. To keep a large difference in gas pressures, we exhale the carbon dioxide produced by our body, and use the oxygen inhaled by our body. The branch from the pulmonary artery feeds deoxygenated blood to the alveolar capillaries, and the pulmonary vein branch takes the oxygenated blood back to the heart. Oxygens solubility in the blood is rather low, so we use an iron-containing ring that can bind oxygen. This polypeptide with the heme rings is known as hemoglobin. The hemoglobin binds 4 oxygen atoms with its 4 perforin rings. Red blood cells are specialized, having lost their nuclei, to become simply bags of hemoglobin. Hemoglobin has 2 alpha chains and 2 beta chains, each containing a heme group. Each erythrocyte, red blood cell, contains 280 million hemoglobin molecules. In order to bring oxygen to our tissues, we bind oxygen to the heme groups of hemoglobin. Red blood cells contain 280 million hemoglobin molecules, each capable of holding 4 oxygen molecules. In a sigmoidal curve, y first changes slowly, then changes rapidly over a short change in x, then y changes slowly again. Oxygen saturation of hemoglobin as y against the pressure of oxygen in the tissue is an example of a sigmoidal curve. Most of the time at 40 mm Hg pressure of oxygen in the tissue, the hemoglobin only drops off one oxygen molecule, remaining 75% saturated. But between 20 and 40 mm Hg, large amounts of oxygen are released from hemoglobin in response to small decreases in the oxygen pressure. This allows the body to respond to changing amounts of oxygen by making hemoglobin release more of its held oxygen as needed. We produce carbon dioxide as a waste product of cellular respiration. Carbon dioxide combines

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 84

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

with water on its own, to produce carbonic acid, which dissociates into a proton and a bicarbonate ion. Therefore, when more carbon dioxide is produced in exercise, the pH of the blood is lowered (more acidic). Hemoglobin is responsive to changes in acidity, becoming more likely to drop off oxygen in low pHs. Human fetal hemoglobin is more likely to hold on to oxygen than human maternal hemoglobin, and llama hemoglobin holds on to even more because it requires its stores of oxygen and is used to a lower amount of oxygen. There is a difference in the oxygen affinity of the two hemoglobins: while maternal hemoglobin has 2 beta chains and two alpha chains, the fetal hemoglobin has 2 gamma chains and 2 alpha chains. Adult hemoglobin drops off oxygen to the tissues at pressures where the fetal hemoglobin would pick it up. The requiring of oxygen-carrying hemoglobin is due to the fact that only 1% or 1.5% of oxygen dissolves in the blood plasma the hemoglobin is needed to carry the rest. But carbon dioxide has greater solubility and 7-10% dissolves in the blood plasma. In order to maximize the rate of carbon dioxide diffusion to the blood from the tissues, we keep the carbon dioxide concentration in the blood low through two distinct ways: hemoglobins polypeptide chains bind to approximately 23% of the carbon dioxide (which causes hemoglobin to release more oxygen in response to the carbon dioxide-signaled need for oxygen), and carbon dioxide is converted by carbonic anhydrase (located in the red blood cells) to carbonic acid, which becomes bicarbonate ion, which is the way that most (approximately 70%) of the carbon dioxide is ferried through the bloodstream. When bicarbonate ions are ejected from the red blood cell, chloride ions are allowed to enter the blood cells to balance charge. Next to the lungs, carbonic acid is converted back into carbon dioxide by carbonic anhydrase. Carbon dioxide is released from hemoglobin, and the rest diffuses into the alveoli across the respiratory membrane. May 17 Notes: External respiration: pulmonary gas exchange. Due to the gradient of oxygen, the lower partial pressure on the inside drives oxygen to move by diffusion. Most, 98.5%, of oxygen is taken up by hemoglobin-containing red blood cells. The rest, 1.5%, dissolves in the plasma. Carbon dioxide moves down its gradient, from high concentration in the cells to low concentration outside, through dissolution (7%), binding to hemoglobin (23%) and conversion by carbonic anhydrase to bicarbonate ions (70%). Stem cells are different from somatic cells. Some characteristic properties of these cells: 1. It is not itself terminally differentiated (that is, it is not at the end of a pathway of differentiation). They are multipotent because they retain the capacity to differentiate down several different developmental pathways. They are restricted, though, in that a hemapoietic stem cell in the body can only become a leukocyte, an erythrocyte, or a megakaryocyte, restricted to a blood cell lineage. However, these are more cell types than the average terminally-differentiated non-stem cell is capable of becoming. 2. It can divide without limit (or at least for the lifetime of the animal). Our body requires the ability to make more blood cells, or skin cells, or other body cells. However, adult stem cells do not necessarily divide quickly, nor do they divide without proper signaling from other cells or their surroundings. They are not out of control. 3. When it divides, each daughter has a choice: it can either remain a stem cell, or it can embark on a course that commits it to terminal differentiation. For example, skin cells

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 85

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

remain stem cells while attached to the basal lamina, but begin to differentiate when no longer attached to it. Embryonic stem cells are not only multipotent, they are pluripotent they can become any of 220 different cell types. The embryo becomes a blastocyst, which is hollow in the center. There is an inner cell mass. So to figure out what these cells are, they performed an experiment. They pulled out some of these cells and implanted them into a recipient blastocyst. The injected cells became incorporated in the inner cell mass of the host blastocyst. The blastocyst develops in the foster mother into a healthy mouse the ES cells may contribute to any tissue, and do. Embryonic stem cells can be coaxed into almost any cell lineage in cell culture (in vitro) as well as growing into any cell in a mouse (in vivo). All that is needed to coax these cells down a particular pathway is different combinations of signaling molecules. In culture, the inner cell mass cells may be given different signals. Retinoic acid turns them into neurons. Retinoic acid along with insulin and thyroid hormone makes an adipocyte, or fat cell. Macrophage colonystimulating factor, along with interleukin-1 and interleukin-3. Dibutyryl cAMP along with retinoic acid turns the stem cells into smooth muscle cells. Fibroblast growth factors, along with epidermal growth factor and platelet-derived growth factors create astrocytes and oligodendrocytes. Adult stem cells are less pluripotent. At a steady state 50% of daughter cells must remain as stem cells. Adult stem cells usually divide at a slow rate. A bone marrow stem cell is an example, becoming lymphoid or myeloid stem cells and then other blood cells. Some dedifferentiation can also occur. The experiment that proved this produced a lamb, Dolly. Cultured mammary cells from one animal were semistarved, arresting the cell cycle and causing dedifferentiation. One was fused with a denucleated egg cell from an ovary of a second sheep. The nucleus of the mammary cell was grown in culture to become an early embryo, and implanted it in the uterus of a third sheep. Embryonic development occurred, and a lamb was born. It was genetically identical to the mammary cell donor (and named Dolly after Dolly Parton, a girl with large, um, mammary cells.) Scientists thus proved that the instructions (DNA) housed in a terminally-differentiated cell (mammary cell) could, under the right circumstances (starvation of the mammary cell in culture followed by fusion with a denucleated egg cell) direct the development of a whole new organism, proving that a terminallydifferentiated cell may be differentiated. Dolly the sheep was the clone of an adult sheep whose mammary cell nucleus directed the development of Dolly. However, Dolly the clone did not live a normal lifespan. She died younger than normal, and developed some diseases of old age at an earlier age. A better method of embryonic stem cell creation is done by taking adult skin cells, and using retroviruses to inject the skin cells with various genes. The genes somehow reprogram the cells to become stem cell-like cells, called induced pluripotent stem cells. Although these dont have the same powers of embryonic stem cells, they do have some. Dr Yamanaka reprogrammed mice skin and hair cells into iPS cells with 4 genes that were integrated by retroviruses into the genome. Later 4 genes were introduced into mouse skin and hair cells on a non-integrating piece of a virus so that there would be no permanent record of this 4-gene introduction. Research whittled the 4 genes down to 3 that were sufficient to reprogram the skin and hair cells, and then from 3 genes down to 2 genes. Research went on from there to introduce proteins instead of the genes to reprogram the terminally differentiated cells into

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 86

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

induced pluripotent stem cells (iPSC). The idea was to turn the clock back on these cells with the least amount of manipulation possible. The hope was that the iPSC would bear the faintest trace of scientific intervention and manipulation. However, the iPSC still do not exactly behave as embryonic stem cells do. So much remails These cells give a wonderful look toward the future, one where we can test medications on the cells of a particular diseased individual before testing the medication on the diseased individual himself. A future where we wont have to worry about government regulation of stem cell research. But now we are in somewhat of a future, a future where we no longer have to look with fear and dread at the next Tuesday or Thursday night, afraid of Alaie. Because we are now finished with Alaies BIOL102. It has been a wonderful semester, and year, of writing these notes. Once I finish adding pictures, these notes should be over 100 pages long.

Disclaimer: I do not mean any offense to anyone with anything written in these notes. Any non-Biology-related comment is
intended only in good fun, so that students will not be bored to sleep by the 100 pages of Biology notes. Please dont take offense. Exam Questions: 1. Which of the following statements is true if the guard cells in a typical C3 plant begin to pump out protons? a) The plant is protecting itself against dehydration. b) The plant will soon undergo the Calvin cycle. c) The plant requires O2. d) The neighboring epidermal cells are in danger of dehydration. e) It is nighttime. 2. Water will enter a plant cell: a) Until the cell wall exerts a negative pressure equal and opposite to the solute potential of the cell. b) From a solution if the water potential of the plant cell is higher than the water potential of the solution.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 87

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

3. 4. 5.

6.

7. 8. 9.

1.

2.

c) If the solute concentration of the plant cell is lower than the solute concentration of the surrounding solution. d) If the pressure potential of the cell is negative enough to lower the water potential of the cell below the water potential of the surrounding solution. e) None of the above. Was serving dinner, didnt get the question :p Was serving dinner There would be net movement of water through the semipermeable membrane from a side containing more solute (side A) to a side containing less solute (side B) if: a) A positive pressure of sufficient force was applied to the side with less solute. b) A negative pressure of sufficient force was applied to side B. c) A negative pressure of sufficient force was applied to side A. d) Additional water is added to side B. e) Additional salt is added to side A. Recall that Hershey and Chase radio-labeled the proteins of bacteriophages, and allowed them to infect bacteria. After separating the empty phages from their attachment to the bacteria and spinning the mixtures, the radioactivity was found in the supernatant, but not in the pellet. This experiment proves that: a) DNA is the genetic material. b) Proteins are the genetic material. c) Proteins are not the genetic material. d) DNA is not the genetic material. e) A and C. Drawing Drawing If primase is currently synthesizing an oligonucleotide primer, you know that a) Deoxyribonucleoside triphosphates will serve as the substrates. b) The oligonucleotide primers will soon become a permanent part of the new strand. c) A leading strand is being synthesized. d) A lagging strand is being synthesized. e) You cannot definitely know any of the above. A G-protein has just bound a G-protein coupled receptor. Which of the following must be false? a) This G-protein may be about to exchange its bound GDP for GTP. b) This G-protein may have just bound GTP. c) This G-protein may have only recently hydrolyzed GTP d) This G-protein may have only recently bound the signaling molecule. e) There are no false statements above. A G-protein that is unable to ___ would be unable to ___. a) Phosphorylate its bound GDP; get activated. b) Hydrolyze its bound GDP; turn itself off. c) Release its bound GTP; turn itself on. d) Release its bound GDP; turn itself on. e) Hydrolyze its bound GTP; turn itself on.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 88

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

3. A cell is a target for soluble signaling molecules A, B, and C. Another cell is also a target of these three signaling molecules. From the information provided you know: a) Both cells are likely cells that belong to the same tissue type. b) One cell is likely the descendant of the other cell. c) Both cells will respond in an identical fashion to the binding of at least one of the three signaling molecules. d) One cell may alter gene transcription in response to the binding of the signaling molecules while the other cell does not. e) None of the above. 4. Which of the following statements about the receptors on a single cell in a multicellular organism is likely true? a) This cell exclusively uses G-protein coupled receptors to bind polar signaling molecules. b) This cell is likely to have all of the different receptors that bind adrenaline on its surface. c) This cell is able to bind steroid signaling molecules or polar signaling molecules, but not both. d) This cell is able to bind both steroid signaling molecules and polar signaling molecules but not at the same time. e) This cell is able to bind polar signaling molecules with either G-protein coupled receptors or tyrosine kinase receptors. 5. Two cells of the same tissue bind signaling molecule A. A short while later, one cell divides while the other cell does not. Which of the following provides the least plausible explanation for this occurrence? a) The cell that divides has sustained a mutation that knocked out the function of one allele of a tumor suppressor gene. b) The cell that divides bound additional signaling molecules. The resting cell did not bind additional molecules. c) The cell that remains at rest has bound additional signaling molecules. The dividing cell did not bind additional molecules. d) The cell that divides sustained one mutation in a proto-oncogene that converted it into an oncogene. e) None of the above. 6. You are culturing both normal epithelial cells and cancer epithelial cells in the lab, but think you may have mixed up the samples. Which of the following would allow you to distinguish these cells from one another best? a) Allowing the cell cultures to grow for a while to see if one culture stops dividing once it has formed a single layer of cells while the other culture keeps dividing. b) Checking the cells a day later to see if the samples divided. c) Denying both cell cultures basic growth media for a while to see if either cultures survives. d) Denying oxygen to both cultures to see if one culture grows new blood vessels e) Checking the medium a day later to see if either culture secreted signaling molecules.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 89

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

1. A cell has suffered two mutations in cancer critical genes. This cell may be/have all of the following except: a) This cell may have gained the ability to metastasize. b) This cell may have a division advantage over its neighbors. c) This cell may be ess likely to commit programmed cell death. d) This cell may have altered the function of one of its G-proteins. e) This cell may be more likely to acquire additional mutations in the future. 2. A point mutation that leads to the over-production of a functional tumor suppressor protein would affect the cell that had sustained this mutation in the same way as: a) A mutation converting one allele of a proto-oncogene into an oncogene. b) A mutation that knocked out the function of one allele of a proto-oncogene. c) A mutation that knocked out the function of one allele of a tumor suppressor gene. d) A mutation that reactivated the telomerase gene. e) A mutation that knocked out both alleles of a gene involved in apoptosis. 3. Two cancer cells are taken from different areas within a solid tumor and analyzed. Which of the following statements is most likely false? a) The two cancer cells do not have an identical number of mutations in cancer critical genes. b) The two cancer cells do not share any of the same mutations in cancer critical genes. c) The two cancer cells do not contain the same number of chromosomes. d) The two cancer cells do not have the same rate of division e) They are all equally true. 4. A normal liver cell ____ while a cancer cell ____? a) Divides in response to signals from other cells; is not signaled by other cells. b) Is usually resistant to committing apoptosis; is susceptible to apoptosis. c) Can survive and reproduce in foreign tissue; cannot survive and reproduce in foreign tissue. d) Requires attachment to other cells and the extracellular matrix to survive; can survive and reproduce without such attachment. e) Has active telomerase; does not have active telomerase. 5. Which of the following statements about the hypothalamus is true? a) With respect to hormonal regulation, the hypothalamus is not involved in any negative feedback loops. b) With respect to hormonal regulation, the hypothalamus is not involved in any positive feedback loops. c) The hypothalamus does not receive any sensory input from the nervous system. d) The hypothalamus controls the release of every hormone released by the nterior pituitary. e) There is more than one correct choice above. 6. Hormone A works to lower the concentration of substance X in the blood. Consider that hormone B is an antagonistic hormone of hormone A. Which of the following is true? a) Hormone B works to increase the concentration of X

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 90

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

b) B works on c) Hormone B d) A and B e) A, B, and C 7. During a single idealized 28-day cycle, you would expect: a) Many secondary oocytes do complete meiosis 2 in preparation for fertilization. b) One secondary oocyte to complete meiosis 2 in preparation for fertilization. c) Many primary oocytes to complete meiosis 1 in preparation for ovulation. d) One primary oocyte to complete meiosis 2 in preparation for ovulation. e) None of the above. 8. Which of the following statemenets about human female reproduction is false? a) FSH released during the follicular phase of the ovarian cycle indirectly leads to an increase in estrogen levels. b) The highest monthly levels of progesterone inhibit the release of FSH c) The highest monthly levels of estrogen inhibit the release of FSH d) The highest monthly levels of FSH are produced before ovulation e) There are no false statements about human female reproduction above. 9. A sperm cell undergoes the acrosomal reaction in order to: a) Block other sperm from fertilizing the egg. b) Become capacitated. c) Finish its maturation. d) Stimulate the secondary oocyte to complete meiosis. e) None of the above. 10. A late spermatid has a total DNA amount equivalent to which of the following? a) The first polar body formed. b) A secondary spermatocyte. c) A secondary oocyte. d) The polar body formed upon fertilization. e) None of the above. 11. Which of the following statements concerning the immune system and our external defenses is false? a) Non-specific macrophages can internalize and clear from our bodies large quantities of only two or three types of bacteria. b) The acidity of our skin inhibits the growth of certain bacteria. c) Complement proteins assemble into pore complexes in the lipid bilayer of some pathogens. d) Mucus secretions trap pathogens, blocking their entry into the body. e) There are no false statements above. 12. Which of the following statements about the non-specific immune system is false? a) Secretion of antimicrobial proteins help kill bacterial pathogens that tryto enter the body at openings around the eye. b) An example of an innate defense is mucus secretions on our mucus membranes. c) Most pathogens can cross our skin. d) Phagocytic cells aid in the clearance of pathogens that enter our body.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 91

BIOL102 Notes Professor Adrienne Alaie

Spring 2011

1.

2.

3.

4.

5.

6.

e) Complement proteins remain inactive until they encounter pathogens. Which of the following antigen-presenting cells would be most readily recognized by a cytotoxic T cell? a) A cell that displays self-peptide (exclusively) in its MHC 1 molecules. b) A cell that displays self-peptide (exclusively) in its MHC 2 molecules. c) An immune cell that displays some foreign peptide in its MHC 1 molecules. d) An immune cell that displays some foreign peptide in its MHC 2 molecules. e) A cell that displays foreign peptide (exclusively) in its MHC 2 molecules. Pathogen X lives and replicates extracellularly. Given that information which of the following statements is most likely true? a) The specific immune response will not get activated. b) The non-specific immune response will not be initially involved in fighting this pathogen. c) The cellular arm (cytotoxic Ts) of the specific immune response will be chiefly responsible for fighting this pathogen. d) The humoral arm (B cells) of the specific immune response will be chiefly responsible for fighting this pathogen. e) None of the above. Which of the following statements about a B cell interacting with a Helper T cell is true? a) This B cell will secrete antibodies while still bound to the helper T cell. b) This B cell will become a memory cellwhile still bound to the helper T cell c) This B cell will be killed as a result of its interaction with the helper T cell. d) The B cell is presenting endogenously-derived foreign peptide to the helper T cell in its MHC 2 molecules. e) This B cell is presenting exogenously-derived foreign peptide to the helper T cell in its MHC 2 molecules. An antibody bound to a virus may: a) Lyse the virus directly. b) Signal to the cytotoxic T cell so that it comes and kills the virus. c) Direct the plasma cells to secrete more antibodies. d) Mark the virus as a target for clearance by a macrophage. e) Stimulate the virus to commit programmed cell death. Pressure in the right ventricle must be highest when: a) Pressure in the coronary arteries is lowest. b) Pressure in the aorta is highest. c) Pressure in the right atrium is highest. d) The AV valves are open. e) C and D. All of the following must be true when the AV valves are open except: a) The semi-lunar valves are closed. b) The ventricles are filling. c) The pressure in the ventricles is comparatively low. d) The pressure in the atria is at its highest. e) There are no exceptions above.

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 92

BIOL102 Notes Professor Adrienne Alaie


7.

Spring 2011

By Barukh Rohde, questions to barukh94-school@yahoo.com

Page 93

You might also like