BSCI420 Final

keratin

Hair is made from rigid, fibrous ___________________ molecules secreted by stem cell progenitors in the follicle bulb.

mesenchimal cells

In addition to hemopoietic adult stem cells, the bone marrow contains different adult stem cells that are called ______________________.

niche

A __________________ is a tissue site that provides the necessary conditions for the maintenance of adult stem cells.

pH

A common mechanism for dissociating ligands from receptors after endocytosis is a reduction in ___________________________.

semi-autonomous

Because many genes necessary for mitochondrial function and maintenance have been lost to the nucleus, mitochondria are considered to be __________________________ regarding their ability to replicate.

Compare and contrast respiration and photosynthesis, briefly describing the following: What are the major molecular complexes involved in each process, and where they are located in cells. Which molecules are consumed during each process, and which are produced. Which of the two processes generates ATP, and what is the molecular complex responsible for ATP generation.

Cellular respiration is the usage of glucose and other carbohydrates to produce ATP in eukaryotes, by way of mitochondria. This process relies on ATPase and produces CO2 and water as its primary byproducts. This occurs in the mitochondria and most of the ETC proteins are located on the inner-mitochondrial membrane (although parts of the process like glycosylation occur elsewhere. By contrast, photosynthesis occurs mostly in the thylakoid membranes of chloroplast to produce large sugar and carbohydrate molecules that will eventually be used in cellular respiration. For this process, the ETC is stimulated by photons of light in order to capture energy and fix carbon using chlorophyll. This process consumes CO2 and water and results in the byproduct of O2. Both of these processes are highly reliant on one another in a cycle to ensure that resources are always available.

photosystems

Chloroplasts have two _____________________________ that harness energy from the sun to extract electrons from water.

coat

Clathrin in an example of a ______________________ protein that deforms membranes to form vesicles.

chloroplasts

During evolution, photosynthetic bacteria are thought to have been engulfed by primitive cells, originating the _________________________.

Describe the main steps of the procedure used to generate transgenic or gene knock-out mice, starting from pluripotent embryonic stem cells.

Embryonic stem cells can be taken from one mouse blastocyst, then be genetically altered using different gene editing techniques (often CRISPR/Cas9). Then these edited ES cells can be cultured and reintroduced into a healthy mouse embryo. Once these cells fuse with the embryo, it will grow into a chimeric mouse. If the edited ES cells become the germline cells, then this chimeric mouse can reproduce offspring in which all cells have that genetic change.

fat cells

Fibroblasts are differentiated cells, but they retain a limited capacity of transforming into other cell types, such as ________________________.

oxygen

In mitochondrial oxidative phosphorylation, high-energy electrons derived from NADH pass along the electron transport chain. The last component of this electron transfer chain, called cytochrome oxidase complex, donates four electrons to ____________________, generating H2O in the process.

enteroendocrine cells

Intestinal _________________________ secrete hormones that regulate the sense of hunger.

disulfide bonds

Mature, active insulin has two peptide chains linked by _____________________.

platelets

Megakaryocytes are cells from the hematopoietic lineage that give origin to _______________________.

Where are melanocytes located in the skin? What is a morphological feature of melanocytes that facilitates their role in transferring granules containing melanin pigment to keratinocytes?

Melanocytes are located at the base of the epidermis, between the epidermal and dermal layer of the skin. These cells are capable of transferring granules of melanin pigment to keratinocytes, because they are lysosome regulated. In other words, tiny sacs, called cellular projections, of these pigments are released from the melanocyte and then fuse with the cell membrane of the target keratinocyte in order to produce a pigmented keratinocyte. These pigments then remain in the keratinocyte until they are destroyed by some outside influence such as UV light, chemicals, or heat.

dynamin

Mitochondria divide through the action of a GTPase protein that belongs to the _____________________ family.

lipid droplets

Most organelles in cells are surrounded by a phospholipid bilayer. One exception are the _________________________, which are surrounded by only one layer of phospholipids.

polarity

Motor proteins bind to actin or tubulin polymerized filaments that function as tracks. Motor proteins recognize the _____________________________ of these filaments as a way to determine direction of movement.

ATP

Myosin is a motor molecule that uses the energy of ___________________ hydrolysis to move cargo.

sinusoids

Newly formed blood cells enter _______________________, blood vessels within the bone marrow.

GPI

One way by which proteins can be attached to membranes is through _________________ anchors.

Compare and contrast osteoclasts and osteoblasts in terms of the cell types from which they originate, their cellular structure and their function.

Osteoclasts are multi-nucleated cells that develop when macrophages fuse together. These cells are high in lysosomal enzymes, which get secreted onto the bone's surface causing degradation. Normally this is important for normal bone health, but when osteoclasts are over productive or osteoblasts are underproductive, it can lead to osteoporosis. The osteoblasts on the other hand are distantly derived from stem cells that undergo a lot of mechanical change. They are single-nucleus cells with very large ERs that secrete collagen and hydroxyapatite used for formulation of the bone matrix.

Compare and contrast the role of pluripotent stem cells and adult stem cells in a living organism, addressing the following points: Where are they found in an animal? What is their biological role during the whole life of an organism, beginning with the embryo? How do they vary in their capacity to give rise to differentiated, specialized cell types?

Pluripotent stem cells in an animal are stem cells that have the ability to transform into nearly any type of cell, but are generally very rare in an adult human. Usually unless induced, pluripotent stem cells only exist in the very early stages of an embryo before the blastocyst has formed different cell layers. Their role is thus to regulate the gradually development of the body into all of its various tissues. By contrast, an adult stem cell is found in many places in the body, including in hair follicles, bone, and the gut lining. These adult stem cells are often multipotent, meaning they can arise into multiple different types of cells, although some are unipotent. However, the range of cells they can form is usually limited based on a specific set of growth factors located in their niche so they can only give rise to cells that would be helpful based on their location. I.e. goblet cells in the gut. Both forms of stem cells are important for growth and development though, since most differentiated cells are unable to replicate themselves.

Wnt

Pre-cancerous cell growths called adenomas can occur in the intestinal epithelium because of mutations that prevent cells from turning off ____________________ signaling.

GTPase

Rabs are proteins with _________________________ activity that bring vesicles closer to their specific target membranes by interacting with tether molecules.

Membrane fusion is mediated by SNARE molecules. Describe how SNARES promote membrane fusion, and how SNARES can provide specificity of fusion between the different cellular compartments. Also, give an example of another type of molecule, in addition to SNARES, that also regulates the specificity of fusion between cellular compartments.

SNAREs are used to bind an incoming vesicle to the target membrane. They lock onto the vesicle and facilitate the fusion of the vesicular membrane with the target membrane by pinching the membranes together. Then once the membranes have fused, the SNAREs dissociate via ATPase activity. They also provide specificity, because each target membrane has a unique SNARE, with specific coding. This means that a vesicle targeted for a lysosome could not attach to the plasma membrane. Another molecule that provides specificity in fusion between compartments are the Rab proteins, which have more than 60 unique forms depending on target location. These are important for guiding the vesicle to the correct location.

How do statin drugs work in lowering the amount of bad cholesterol in circulation?

Statin drugs work to lower the amount of LDL in circulation by being competitive inhibitors with reductase. This prevents Mevanolate from forming, which in turn blocks the production of more cholesterol. Then, because intracellular cholesterol levels have been severely reduced, the cells increase the receptors for LDL in the bloodstream in order to increase uptake from the extracellular space. This in turn reduces the amount of LDL particles in the bloodstream, and since statins only work in the liver, the uptaken LDL can be disposed of.

Both statins (drugs that reduce cholesterol in the bloodstream) and bisphosphonates (drugs that reduce bone degradation) are hydrophilic molecules, which do not easily diffuse through the membrane of cells. So how do these two classes of drugs enter cells? And what ensures that statins mainly work in the liver, and bisphosphonates in bone?

Statins and primarily enter liver cells through the use of a liver-specific membrane transporter called OATP1B1. This transporter allows the statins to pass through into the inner part of the liver cell, but isn't present on the surrounding cells, so statin cannot enter them. Thus, the statins only work to control LDL uptake in the liver, which is where it is most important to occur for excretion. Bisphosphonates only work in the bone, because although they must bind to mineralized bone before they can work.

LDL

Statins are drugs that lower the total amount of cholesterol circulating in the blood by stimulating receptor-mediated uptake of ___________________ particles.

What is the connection between stem cells and grey hair?

Stem cells and grey hair are connected, because melanocytes are generated from stem cells in the hair follicles. As these stem cells are gradually worn out/lost over time, there is no longer a production of melanocytes, and thus the generation of pigment to be transferred into the keratinocytes ceases and hair loses its color.

The "great oxygenation event" refers to the moment in the history of the Earth, about 1 billion years ago, when oxygen produced by photosynthetic cells was able to accumulate at significant levels in the atmosphere. However, the first photosynthetic cells are thought to have appeared much earlier, about 3.5 billion years ago. Why it took so long for oxygen to accumulate in the atmosphere?

The Great Oxygenation event took so long to occur after the first appearance of photosynthetic cells, because much of the oxygen being produced was absorbed by the oceans, via binding to iron. Because this iron oxidation was so gradual, it took a very long time for the ocean to become saturated. It wasn't until this saturation occurred that oxygen could begin to accumulate in the atmosphere.

acidification

The V-type proton pump is an important H+ proton transporter responsible for _______________________ of the lumen of lysosomes.

calcium

The ___________________ concentration in the cytoplasm of cells is kept low, in the nanomolar range, but extracellularly and inside the endoplasmic reticulum it is much higher, in the millimolar range.

satellite

The adult stem cells that function in the regeneration of skeletal muscle fibers are known as _______________________ cells.

What are the two types of experimental manipulation that can make the genetic information in the nucleus of a differentiated cell return to a pluripotent, stem cell state? Describe briefly the main steps of these two experimental techniques.

The first primary technique is to reintroduce the four main transcription factors Klf, SOX, Oct, and Myc into differentiated cells. The presence of these transcription factors will induce cells to produce more of their own, and eventually the positive feedback mechanism enables these differentiated cells to transform back into an undifferentiated state called an induced Pluripotent Stem Cell. The other strategy is to take the nucleus of a differentiated cell and transfer it back into an oocyte that has had its nucleus removed. These oocytes have the proper chemical environments to enable silenced genes of a differentiated nucleus to be transcribed again.

Briefly describe the steps involved in atherosclerotic plaque formation, a pathological process that leads to heart attacks and strokes.

The first step of atherosclerotic plaque formation is damage to the interior walls of an artery or vein. Once this wall is damaged, LDL accumulates on these microwounds and begins to form a buildup and oxidize. These oxidized LDL molecules lead to the recruitment of macrophages in an attempt to battle the perceived illness, but when the macrophages absorb the cholesterol granules, they turn into foam cells. After all that, the foam cell buildup is covered by smooth muscle cells as a sort of cap, which secures the plaque in place.

Stem cell technology may one day make it possible to produce human organs in animals to be used for transplantation. Scientists already succeeded in generating a rat pancreas inside the body of a mouse. However, the rat cells that formed the new pancreas are very different from mouse cells, and normally mammals reject foreign cells and tissues in an acute immunological reaction called graft-versus-host disease. Why was this not a problem when the rat pancreas developed inside a mouse?

The introduction of a rat pancreas in a mouse was not a problem, because the rat pancreatic cells were introduced into the mouse blastocyst. This was early enough in the mouse's development that the cells could not yet produce an autoimmune response. Thus the cells were able to be recognized as a natural part of the mouse's body. If the immune system had already begun to form, the rat pancreatic cells would have been attacked.

What is the major common property of motor proteins that allows them to produce motion?

The major common property of motor proteins that enables motion is their ATPase activity. These proteins bind to ATP, then hydrolyze it into ADP. The energy from the hydrolysis causes them to undergo a conformational change, which in turn enables then to "walk" along their respective filaments. Then they can move great distances by repeating this process.

Mitochondria and chloroplasts are surrounded by two lipid bilayer membranes, and are thought to have originated from bacteria that were engulfed and maintained by ancestral archea cells. What is the experimental evidence that strongly supports the conclusion that mitochondria originated from bacteria?

The major evidence suggesting that mitochondria originated from bacteria is that it has its own set of DNA independent of the rest of the cell. This mitochondrial DNA is passed down maternally, and can be used for genetic tracing. The other major discovery was that mitochondria are capable of their own protein synthesis, because they have ribosomes. Both of these discoveries strongly imply that mitochondria were originally descended from bacteria before being absorbed into the precursors of eukaryotes and thus becoming an organelle.

cytoskeleton

The mobility of transmembrane proteins within lipid bilayers can be restricted through connections between their intracellular domains and the _____________________________.

endoplasmic reticulum

The nuclear membrane is contiguous with the membrane of the _______________________.

The nuclear envelope has elaborate pores that control the passage of molecules in and out of the nucleus. Summarize the regulatory mechanisms that control the movement of proteins in and out of the nucleus.

The nuclear pores are large protein complexes that span both bilayers of the nuclear envelope. They are large enough to allow small hydrophilic and hydrophobic molecules in and out of the nucleus. However, these pores rely on the use of Ran, Ran-GAP and Ran-GEF to control the movement of proteins into and out of the nucleus. Ran has GTPase capabilities, and depending on whether GTP or GDP is bound to it, it will be able to hold a protein (this is based on export and import). The Ran-GAP is used to hydrolyze the GTP on Ran and Ran-GEF is used to exchange the GDP for GTP.

Current legislation in the US does not allow implantation in a woman of an embryo carrying genetic modifications that can be passed on to the next generation. However, some scientists have recommended approval of the "three parent baby" procedure under a specific condition, that would avoid inheritance of DNA that did not come originally from nuclei of the mother's egg and the father's sperm. What is this specific condition, and why does it avoid the problem of passing genetic modifications to future generations?

The only situation in which a three parent baby is permitted, is when the child produced is a boy, with the egg of a donor mother and the nucleus DNA from the original father and mother. This is because the egg donor mother will be the one to pass on the mitochondrial DNA to the child, giving the child three distinct sources of their genome. However, if the child is a boy, then they will not be capable of transferring this "illegal" mitochondrial DNA to their children, and will only pass on the standard nucleic DNA from their two original parents.

hydrophobic

The presence of transmembrane domains in a protein can be predicted by stretches of ________________________ amino acids in its sequence.

glycosylation

The proper folding of newly synthesized proteins in the endoplasmic reticulum is checked through their _______________________.

nucleation

The rate-limiting step in the formation of actin filaments is the ___________________________ of actin monomers.

During traffic through the Golgi apparatus, glycoproteins are modified by addition of sugar residues, trimming of carbohydrate chains, phosphorylation and sulfation. How are these different post-translational modifications achieved in the correct sequence?

These different translational modifications are kept in sequence by the inherent arrangement of the Golgi body. The Golgi is organized is a cis to trans direction, or from reception of proteins from the ER being cis and export from the Golgi being trans. As proteins move through consecutive layers of the Golgi, different modifications are made in succession. In other words, the enzymes responsible are present in graded concentrations across the stack of layers.

Resident endoplasmic reticulum (ER) proteins are tagged with a KDEL amino acid sequence. How are these proteins kept in the ER?

These resident endoplasmic reticulum proteins are kept in the ER by a special recycling process. There are KDEL receptors on the ER and Golgi membranes, that bind to this KDEL sequence. When the resident protein ends up in the Golgi, the receptor recognizes and binds to it and is broken away by COPI. Then the protein is returned in a vesicle to the ER, still attached to the receptor. Once the vesicle rebinds to the ER, the protein breaks away from the receptor and the receptor is used again.

extracellular medium

Topologically, the lumen of endosomes and lysosomes is equivalent to the ________________________ of cells.

stromal cells

_______________________________ help form the bone marrow niche that keeps hematopoietic stem cells in their stem cell state (without differentiating).

Diabetes is a serious disease resulting from an inability to properly regulate glucose levels in the blood. Compare and contrast type 1 and type 2 diabetes, addressing the following points: Which type affects more people in the US. At what age symptoms usually appear. What is wrong in each case, at the cellular level.

Type 2 diabetes is the one that most people think of when they think of diabetes and affects many more people in the US than Type 1. Type 2 is characterized by a resistance to insulin (often caused by a diet high in sugars and little exercise). This is the result of a malfunctioning glucose transporter control pathway. Symptoms generally appear later in life, around the age of 40. By contrast, Type 1 diabetes is not at all related to lifestyle and instead is an autoimmune disorder in which beta cells are selectively attacked so that the body is unable to produce insulin. This form of diabetes almost always appears early in childhood and affects far fewer people in the US.

glucose transporter

When insulin binds to its receptor on the plasma membrane of liver, skeletal muscle or adipose cells, the _______________________ is mobilized to the cell surface from its reservoir in recycling endosomes.

centrioles

___________________ are a pair of short cylindrical arrays of microtubules that function as microtubule organizing centers in cells.

kinesin

___________________ is a motor protein that moves vesicles on microtubule tracks towards the cell periphery (plus ends).

dynein

____________________ is a motor protein that moves along microtubules towards the minus ends, towards the cell interior.

HDL

____________________ particles can extract cholesterol from foam cells in atherosclerotic plaques, so are known as "good cholesterol".

protozoa

_____________________ are an extremely morphologically diverse class of nucleated single-cell organisms.

lipid rafts

_____________________ are plasma membrane microdomains enriched in cholesterol, sphingolipids and GPI-anchored proteins.

Low density lipoprotein

_____________________ particles are complexes of protein, phospholipids and cholesterol that circulate in the blood and are known as "bad cholesterol".

GTP

______________________ hydrolysis is widely used as a molecular switch in the regulation of membrane traffic in cells.

defense peptides

_______________________ capable of killing bacteria are produced by Paneth cells.

organoids

_______________________ made from pulmonary adult stem cells have been used to treat cystic fibrosis.

satellite cells

________________________ are one of the few examples we know of unipotent adult stem cells.

transit cells

________________________ are the progeny of stem cells.

Goblet cells

_________________________ produce mucus that lubricates the intestinal tract.

Paneth cells

_________________________ produce signaling molecules that help maintain the intestinal adult stem cell niche.

platelets

__________________________ result from fragmentation of cellular extensions of a larger cell.

After clathrin-coated vesicles are formed during endocytosis, they pinch spontaneously from the plasma membrane.

false

Both mitochondria and chloroplasts are able to export ATP from its matrix space to the cytoplasm of cells.

false

Channels are slower than transporters in moving molecules across membranes.

false

During evolution, the uptake of photosynthetic bacteria that gave origin to chloroplasts is thought to have happened before the engulfment event that gave rise to mitochondria.

false

GPI-anchored proteins have stretches of amino acids that extend across the plasma membrane into the cell interior.

false

Hydrophilic molecules can easily diffuse across lipid bilayers to enter the cytosol of cells.

false

Introducing one transcription factor into skin cells is sufficient to induce them to de-differentiate and become induced pluripotent stem (iPS) cells.

false

Mitochondria found in embryonic cells were inherited from both the mother's egg and the father's sperm.

false

Porphyrin rings containing iron at the center (heme) are present in both mitochondria cytochromes and in chloroplast chlorophyll molecules.

false

The cholesterol-loaded foam cells that form atherosclerotic plaques originate from endothelial cells, which line the blood vessels.

false

The engulfment of pathogens by phagocytic cells is mediated by the polymerization of tubulin filaments (microtubules).

false

Water (H2O) is a side-product of both respiration (oxidative phosphorylation) in mitochondria and photosynthesis in chloroplasts.

false

Actin and the actin motor myosin were first discovered in skeletal muscle.

true

Adult stem cells divide slowly.

true

After a skin wound heals, scars can happen because of the deposition of collagen fibers inside the dermis by fibroblasts.

true

Anagen, the growth phase of the hair cycle, ends when the germinal center of hair follicles is pushed down and the short-lived stem cell progenitors degenerate.

true

Cells that are very active in protein synthesis and secretion have an expanded rough endoplasmic reticulum.

true

Esterification of cholesterol by the enzyme acyl-CoA-cholesterol acyltransferase (ACAT) is important for the storage of cholesterol in lipid droplets.

true

Hair becomes gray because melanocyte stem cells associated with the hair follicle get depleted over time.

true

In addition to its role in making membranes less permeable to water, cholesterol is also a precursor for the biosynthesis of steroid hormones.

true

Mechanical forces such as stretching can open channels in membranes.

true

Mitochondria accumulate in intracellular sites where there is a strong need for energy.

true

Paneth cells reside in intestinal crypts, the same place where stem cells are located.

true

Rubisco is a very abundant enzyme (up to 50% of the total mass of chloroplasts) that catalyzes a central reaction in carbon fixation.

true

Sugar molecules added to phospholipid head groups are always located on the outer layer of the plasma membrane, facing the extracellular space.

true

The ATP synthase is an enzyme located in the inner membrane of mitochondria and in the thylakoid membrane of chloroplasts, where it catalyzes ATP production by rotating like a turbine.

true

The hydrophobic signal sequences that regulate translocation of membrane proteins into the endoplasmic reticulum can be located at different positions within the amino acid sequence.

true

The mammalian tissues with the most vigorous adult stem cell-driven regeneration capacity are the small intestine and the skin.

true

The transport of molecules across membranes by transporters can be active or passive, whereas transport by channels is always passive.

true

Two major events in membrane traffic inside nucleated cells are vesicle budding from one compartment and fusion with another.

true