FINAL REVIEW_ LEARNING OBJECTIVES
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Biology
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Nov 24, 2024
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WEEK 1 LEARNING OBJECTIVES
Discuss how a signal can lead to both
short- and long-term responses.
Signaling cell → Signaling molecule → Receptor protein → Response
(1) Signal binds and the receptor is activated. (conformational change)
(2) Signal transduction occurs where one molecule activates the next
(3) Response: enzyme activity, turning on of genes, signals other cells, or causes
transcription of the proteins.
G-protein coupled signaling is short term.
Ex. activating enzymes or opening ion channels
Receptor kinase signaling is long term.
Ex. activating growth and development, changes in gene expression, or
differentiation cells.
Short-term response:
-
Paracrine signaling
-
Autocrine signaling
-
Cell-to-cell contact
Long-term response:
-
Endocrine signaling
Describe the mechanism of action for a
receptor tyrosine kinase pathway.
(1) Inactive Receptor
The signal molecules bind to the extracellular portion of the receptor.
(2) Dimerization
Causes a conformational change in the cytoplasmic domain which activates the
tyrosine kinase catalytic activity. ATP is also converted to ADP in this process.
(3) Active Receptor
The conversion of ATP to ADP allows each member of the receptor pair to attach
phosphate groups to one another. Essentially, phosphorylation occurs.
(4) These phosphate groups provide binding sites for intracellular signaling
proteins, which activates them.
Define the role of kinases and
phosphatases in cell signaling pathways.
Kinases- enzymes that catalyze the transfer of a phosphate group from ATP to a
substrate (phosphorylation), which activates the protein.
Phosphatases— remove a phosphate group (dephosphorylation), and protein
becomes inactive.
Distinguish the potential for differentiation
of totipotent, pluripotent, and multipotent
stem cells.
Totipotent— can give rise to a complete organism (most potential)
Pluripotent— can become any of the three germ layers (ectoderm, mesoderm,
endoderm). (Less potential)
Multipotent— can form a limited number of specialized cells (least potential)
Evaluate why diffusion and surface area
limit cell size and its implications for large,
multicellular organisms.
As volume increases, surface area decreases.
Bigger cells require more nutrients. However, as they get bigger they cannot hold
much of the nutrients and their ability to discard waste is reduced.
Waste removal is faster in small cells.
Implication: large, multicellular organisms have lots of little cells.
The smaller the surface area to volume ratio, the slower the rate of diffusion
across the surface.
Determine if certain proteins in a signaling
pathway function as phosphatases,
kinases, or neither.
If it adds a phosphate group and activates protein, then it is a kinase.
If it removes phosphate and deactivates the protein, then it is a phosphatase.
If it does neither, then it is neither.
Explain how a signal transduction
pathway can be turned off.
(1) Binding affinity: the length of time a signaling molecule remains bound to its
receptor depends on how tightly the receptor holds on to it. The ligand is released
from the receptor.
(2) G proteins can catalyze the hydrolysis of GTP to GDP and inorganic
phosphate. This means that an active, GTP-bound α subunit in the "on" position
automatically turns itself "off" by converting GTP to GDP. In fact, the α subunit
converts GTP to GDP almost as soon as a molecule of GTP binds to it. Without
an active receptor to generate more active G protein α subunits, transmission of
the signal quickly comes to a halt.
(3) Phosphatases remove phosphate groups deactivating proteins.
(4) Enzymes degrade cAMP, converting the second messenger cAMP to AMP
which no longer activates protein kinase A.
Predict the effect of altering part of a
signal transduction pathway.
When one part of the signal transduction pathway is altered, it affects everything
else downstream.
Interpret data related to different types of
cell signaling pathways.
cell signal (ligand) → receptor activation → signal transduction → response →
termination
Paracrine signaling: short distance (diffusion)
Synaptic signaling: short distance (ligands are neurotransmitters)
Autocrine signaling: cell signals to itself
Endocrine: signals release through bloodstream
Cell-to-cell contact: stuck together, signal can be a transmembrane protein
Predict cell fate based on cell activation of
signaling pathways.
There could be signals that only activate certain genes that limits what the cells
can differentiate to.
Describe the different types of cell-cell
Cell junctions physically connect one cell to the next and anchor cells to the
junctions.
extracellular matrix.
(1) Tight junctions: establishes a seal between cells so that the only way a
substance can travel from one side of a sheet of epithelial cells to the other is by
moving through the cells by a cellular transport mechanism. In other words, tight
junctions prevent transport of material in between the membranes of the cell.
(2) Desmosomes: a button-like point of adhesion that holds the plasma
membranes of adjacent cells together. In other words, they allow cells to adhere
to one another.
(3) Adherens junctions: a beltlike junctional complex composed of cadherins that
attaches a band of actin to the plasma membrane. They use cadherins to bridge
the neighboring plasma membranes via their homophilic interactions.
The cadherins in the adherens junction of one cell attach to the cadherins in the
adherens junctions of adjacent cells. This arrangement establishes a physical
connection among the actin cytoskeletons of all cells present in an epithelial layer
of cells.
(4) Gap junctions: a type of connection between the plasma membranes of
adjacent animal cells that permits materials to pass directly from the cytoplasm of
one cell to the cytoplasm of another. Gap junctions are a complex of integral
membrane proteins called connexons arranged in
a ring. The ring of connexin proteins connects to a similar ring of proteins in the
membrane of an adjacent cell. Ions and signaling molecules pass through these
junctions, allowing cells to communicate.
Adherens junctions and desmosomes provide strong attachments between cells,
but they do not prevent materials from passing freely through the spaces between
the cells like tight junctions do.
The extracellular matrix (outside the cell):
■ Hemidesmosomes: a type of desmosome in which integrins are the prominent
cell adhesion molecules. The extracellular domains bind extracellular matrix
proteins, and the cytoplasmic domains connect to intermediate filaments. These
intermediate filaments connect to desmosomes in other parts of the plasma
membrane. The result is a firmly anchored and reinforced layer of cells.
Define microtubule, microfilament, and
intermediate filament.
Microtubule: a hollow, tubelike polymer of tubulin dimers that helps make up the
cytoskeleton.
Function: maintain cell shape and the cell's internal structure, part of cell
division (chromosome segregation), movement (cilia and flagella), and
vesicle transport
Microfilament: A helical polymer of actin monomers, present in various locations
in the cytoplasm, that helps make up the cytoskeleton.
Function: maintain cell shape and the cell's internal structure, part of cell
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division (cytokinesis), movement (crawling), and vesicle transport
Intermediate filament:A polymer of proteins, which vary according to cell type,
that combine to form strong, cable-like filaments that provide animal cells with
mechanical strength.
Function: cell shape and support, strength and support to tissues under
stress (skin and intestine)
Explain how motor proteins actively move
material around the cell.
Kinesin and dynein are associated with microtubules.
Kinesin— transports towards the plus end of microtubule. A motor protein, similar
in structure to myosin, that transports cargo toward the plus end of
microtubules.
Dynein— away from the plasma membrane, towards the minus end. A motor
protein that carries cargo away from the plasma membrane toward the minus
ends of microtubules. Driven by conformational changes and ATP.
Microtubules are found in cilia and flagella. Microfilaments are associated with
motor proteins. Actin microfilaments and myosin transport in vesicles. Moving
actin filaments inside muscle cells cause muscle contraction.
Explain how cell-cell junctions and the
extracellular matrix (ECM) contribute to
cells' ability to form tissues and organs.
Cell-cell junctions:
-
Junctions allow structure and stability by adherens and desmosomes,
allowing cells to form together by cadherins
-
Tight junctions form shapes as they separate cells from cells and create a
barrier.
-
Gap junctions allow molecules and signals to pass allowing the cell to
function.
Extracellular matrix:
-
Holds cells together, filter materials passing through tissues, help orient
cell movement, chemical signaling.
-
Mutations in the function of the extracellular matrix cause fragile tissues.
Evaluate how changing components of
the cytoskeleton would change cell
structure (shape) and/or function (i.e.,
motility).
- In eukaryotes, an internal protein scaffold that helps cells maintain their shape
and serves as a network of tracks for the movement of substances within cells.
- There are three groups of movers, the motor proteins: kinesin, dynein and
myosin, and three main groups of shapers, the protein filaments: microtubules,
intermediate filaments and actin filaments.
- The protein fibers of the cytoskeleton provide internal support for cells.
**
In addition to providing structural support, microtubules and microfilaments
enable the movement of substances within cells as well as changes in cell shape.
Altered activity of motor proteins can lead to build-up or loss of cellular
components.
Evaluate the effect of modifying cell-cell
junctions or ECM components on tissue
structure and function.
If you compromise the ECM then your skin or epithelial tissues will not have
strength in presence of pressure/stress → bed sores
If adherens or desmosome → no cell to cell adhesion
If hemidesmosomes → then cell can't connect to extracellular matrix
If tight junction → then there would be no boundary for the skin, intestine,
stomach, bladder → and molecules can go right through, there would be no seal
WEEK 2 LEARNING OBJECTIVES
Describe the general structure of a
neuron.
Sensory → Interneurons → Motor
Sensory neuron - receives info from stimulus and send to interneurons
Interneuron - received info from sensory neurons and transmits it to motor
neurons
Motor Neuron - receive info from interneuron, effects response in body
Relate the structural features of a neuron
(i.e., dendrites, axons) to their functions.
Dendrite - receives stimulus from presynaptic neuron. Receives signals from
other nerves, input end of the nerve cell.
Cell body: junction where signals pass from dendrite to axon hillock.
Axon Hillock - start of action potential. Point where signals are summed if the sum
is high enough an action potential gets fired.
Axon - action potential travels down axon. Transmits signals away from nerves
cell body
Myelin sheath - insulate neuron → saltatory propagation. As result, action
potentials "jump" from node to node increasing speed of conduction.
Nodes of Ranvier - exposed sites (lots of ion channels). Exposed axon
membrane sites between myelin sheaths. Concentrated with voltage-gated
Na+/K+ channels
Axon terminal - release neurotransmitters
Explain membrane potential and how it
arises in both neuronal and non-neuronal
cells.
Membrane potential: measurement of charge difference between the inside and
the outside of the neuron.
Resting membrane potential = -70mV (more positive on the outside)
-
More Na+ outside and more K+ inside (K+ leaks out)
Refers to negative voltage across the membrane at rest, mainly due to K+ leak
channels and the negatively charged proteins inside the cell membrane
compared to positive outside membrane. Also, due to the sodium potassium
pump, that removes 3 Na+ for 2 K+, so makes it less positive inside.
Explain the process by which an action
potential is generated and propagated.
(1) Summed or spatial EPSPs (graded potential)
(2) Depolarization in dendrites
(3) Depolarization at axon hillock
(4) Opening of Na+ voltage-gated channels (QUICKLY) and K+ voltage-gated
channels (SLOWLY)
(5) Na+ ions rush in (major depolarization), few K+ leave
(6) Voltage reaches +40mV
(7) Na+ channels shut, K+ channels remain open
(8) K+ ions leave cell
(9) Cell becomes more negative (repolarization)
(10)
Hyperpolarization
(11)
Refractory period (no A.P) → pumps return membrane to resting
potential by pumping out Na+ and pumping on K+
The simultaneous movement of positively charged ions into and out of the cell
would result in a change in membrane potential that would not reach threshold
potential and no action potential would be generated.
Compare and contrast ligand-gated and
voltage-gated ion channels with respect to
their role in signal transduction in a
neuron.
Ligand-gated ion channel - opens when ligand binds (at synapse w/
neurotransmitters). Helps with neuron to neuron communication with release of
neurotransmitters as signal molecules to attach to receptors
Voltage-gated ion channel - opens when voltage reaches (Na+, K+ channels and
calcium channels in axon terminal). Plays a key role when neurons fire action
potentials.
Explain the process by which two neurons
communicate at a synapse.
(1) Action potential makes it to axon terminal
(2) Depolarization activates calcium channels
(3) Vesicles with neurotransmitters fuse with presynaptic membrane
(4) Release neurotransmitters in synaptic cleft
(5) Neurotransmitters bind to receptors in postsynaptic neuron dendrite which
are ligand-gated
(6) Receptors allow Na+/Cl- ions to open changing membrane potential
(7) New AP in postsynaptic cell
After inactivation, neurotransmitters are reabsorbed into presynaptic terminal and
stored in vesicles until next action potential arrives
Discuss how EPSPs and IPSPs are
received and integrated by a postsynaptic
neuron.
EPSP (Excitatory Postsynaptic Potential) - positive change in membrane potential
(depolarization + repolarization), Na+ ions diffuse into cell after neurotransmitters
bind and activate Na+ channels,
STIMULATES ACTION POTENTIAL
IPSP (Inhibitory Postsynaptic Potential) - negative change in membrane potential
(hyperpolarization), neurotransmitters bind and open Cl- and K+ channels, Cl-
diffuses into the cell or K+ diffuses out
INHIBITS ACTION POTENTIAL
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Evaluate how multiple signals will be
integrated by a postsynaptic neuron that
has formed synapses with two or more
presynaptic neurons.
Temporal Summation - multiple EPSPs arrive quickly at single synapse
Spatial Summation - multiple ESPS arrive at different locations simultaneously
→ generates an action potential
Cancellation - EPSPs and IPSPs cancel each other out
Postsynaptic membranes contain multiple receptors, and can bind many different
neurotransmitters.
→ when EPSP and IPSP both arrive on postsynaptic membrane = action
potential generated
→ temporal summation on postsynaptic = action potential
Cell sums all the inputs -> if summed input breaches threshold potential, an
action potential is fired at axon hillock
Temporal Summation = summed over time, frequency of synaptic stimuli
determines action potential
Spatial Summation = summed over space, number of synaptic stimuli received
from different regions of the postsynaptic cell's dendrites determines action
potential
Predict how a charged molecule will move
across a semipermeable membrane in the
presence of an electrochemical gradient.
Chemical gradients come from concentration differences.
Electrical gradients come from charge separation.
Electrical gradients are stronger than chemical gradients.
Charged molecule will move down its electrochemical gradient (ie. if positive will
move to negative side)
Predict how addition of drugs or the
introduction of mutated proteins will alter
membrane potential, excitability, and/or
signal transmission
Opioids bind to ligand-gated channels on postsynaptic cell → increased ion
movement → increased signal → cell destroys receptors to decrease signal →
need heavier dose of opioid to increase signal (get the same feeling)
+drugs affecting CNS causes decrease in postsynaptic cells and needs higher
doses
+ drugs interrupting membrane potential/encouraging leaks makes neurons
unable to fire or overfire
Describe the global organization of the
human nervous system.
Central nervous system-- brain, spinal cord
Peripheral nervous system-- sensory and motor nerve
PNS split into:
Somatic (Voluntary component)-- sensing and responding to external stimuli =>
split into motor nerves (efferent toward PNS) and sensory (afferent toward CNS)
Autonomic (Involuntary component)-- regulate internal bodily functions =>
sympathetic (flight or fight) and parasympathetic (rest and digest)
***
Afferent
neurons carry information from sensory receptors of the skin and other
organs to the central nervous system (i.e., brain and spinal cord), whereas
Efferent
neurons carry motor information away from the central nervous system
to the muscles and glands of the body.
Relate the major regions of the brain,
including the hypothalamus, thalamus,
and sensory cortex to their respective
functions.
Frontal Lobe- decision making and planning
Parietal Lobe- body awareness, ability to do complex tasks (ex. dressing)
Temporal Lobe- processing sound
Occipital Lobe- processing visual information
Primary Motor Cortex- complex, coordinated behaviors by controlling skeletal
muscle movements
Primary Sensory Cortex- integrates tactile information from specific body regions
and relays this information to the motor cortex
Cerebellum: balance; coordinates complex motor tasks with sensory and motor
info
Brainstem: initiates and regulates motor functions such as walking, posture,
breathing and swallowing. Connects brain to spine => controls the flow of
messages between the brain and the rest of the body
Hypothalamus- endocrine function, hormone production, autonomic function
Thalamus- relay motor and sensory signals to the cerebral cortex
Compare and contrast the sympathetic
and parasympathetic divisions of the
autonomic nervous system.
*** They cannot occur at the same time because they affect the same pathway.
Sympathetic “fight or flight”
-
accelerated heart rate, dilates pupils, stimulates glucose release
-
arousal and increased activity
-
nerves leave CNS from middle region of spinal cord
Parasympathetic “rest and digest”
-
constricts pupils, slows heart, increases digestion
-
nerves leave CNS from brain via cranial nerves
Explain how the brain receives,
processes, and sends information.
(1) Sensory info received by cranial nerves and spinal cord nerves
(2) Pass through brainstem → thalamus → specialized region in cerebral
cortex
Evaluate which region of the brain has
been damaged in a patient based on a set
Broca's Area - Struggling to produce language but can comprehend speech →
frontal lobe
of symptoms.
Wernicke's - Can't comprehend speech but have no issue producing speech
→ temporal lobe
Predict which branch, parasympathetic or
sympathetic, will respond to different
stimuli.
Scared - Sympathetic
Relaxed or Eating - Parasympathetic
WEEK 3 LEARNING OBJECTIVES
Identify the components of a homeostatic
negative feedback system.
Components of negative feedback:
-
The process in which a stimulus acts on a sensor that communicates with
an effector, producing a response that opposes the initial stimulus.
Negative feedback is used to maintain steady conditions, or homeostasis.
DEFINITIONS:
Stimulus: produces a change in the variable
Sensor: measures/detects change in the variable
Control: analyzes the information from the receptor and determines the
appropriate response to the change
Effector: organs or glands that carry out the response from the control center
Response: the action of the effector that will counteract the stimulus and bring the
variable back to its normal value
In a negative feedback loop, the stimulus and response oppose each other.
Explain how each component of a
homeostatic negative feedback system
contributes to maintaining physiological
stability.
Need each level so that body can maintain stability, without one of the levels,
homeostasis won't be achieved
Stimulus to sensor - Change in the level of something
Sensor to effector- Part of body or cells that detects
Effector to response- Part of body that makes change
Response inhibits sensor - brings it back to the set point
Differentiate between negative feedback
and positive feedback, providing
examples of each.
Negative Feedback
-
the process in which a stimulus acts on a sensor which communicates
with an effector, producing a response that opposes the original stimulus;
this process results in homeostasis
-
Example: High blood glucose right after a meal acts a stimulus to the
pancreas (sensor), which in turn, produces the hormone insulin, which
allows muscle and liver cells (effector) to take up the glucose circulating in
the bloodstream, thus resulting in a lower blood sugar level (response).
Positive Feedback
-
the type of feedback in which a stimulus causes a response that leads to
the enhancement of the original stimulus; this process reinforces itself
until it is interrupted
-
Example: Positive feedback occurs in mammals during birth. When
uterine contractions occur, the hormone oxytocin (stimulus) is released
from the pituitary gland (sensor?), which causes the uterine muscles
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(effector) to contract more forcefully. The uterine contractions, in turn,
cause the pituitary gland to produce more oxytocin causing more
contractions until the offspring is born.
Predict how components of a homeostatic
system will change when part of the
system is perturbed.
Depends on the situation. The process will get disrupted, however.
Apply the concept of negative feedback to
the process of thermoregulation.
Hot:
Temperature rises [Stimulus] -> Thermoregulation center in brain activates
[Sensor] -> Sweat glands release sweat [Effector] -> Temperature decreases as
skin cools from sweat evaporation [Response]
Cold:
Temperature falls [Stimulus] -> Thermoregulation center in brain activates
[Sensor] -> Skeletal muscles rapidly contract, shivering [Effector] -> Temperature
rises as shivering generates heat [Response]
Relate changes in environmental
conditions to changes in physiological or
behavioral responses to temperature
regulation.
Many animals regulate their body temperature through behavior, such as seeking
sun or shade or huddling together for warmth.
→ Endotherms can alter metabolic heat production to maintain body temperature
using both shivering and nonshivering thermogenesis.
→ Vasoconstriction — shrinking and expansion of blood vessels to the skin can
alter an organism's exchange of heat with the environment.
A countercurrent heat exchanger is an arrangement of blood vessels in which
heat flows from warmer to cooler blood, usually reducing heat loss.
Some animals use body insulation and evaporative mechanisms, such as
sweating and panting, in body temperature regulation.
Relate endocrine function to homeostatic
regulation.
The endocrine system plays an important role in homeostasis because hormones
regulate the activity of body cells.
→ The release of hormones into the blood is controlled by a stimulus.
→ The hypothalamus' function in the endocrine system is to control and stimulate
the pituitary gland. The hypothalamus and pituitary gland are connected via a
system of blood vessels. Hormones produced in the hypothalamus travel through
the vessels and stimulate the pituitary gland. The hypothalamus produces
inhibiting or releasing hormones.
→ Our thyroid gland is located in the neck and stimulated by TSH, which is
appropriately called thyroid stimulating hormone. The thyroid is responsible for
metabolism, regulating body temperature, the development of the nervous
system, reproductive system and heart function. The thyroid secretes two
hormones, T3 and T4, which are collectively called TH (thyroid hormone).
→ The pancreas is also part of the endocrine system. Insulin and glucagon are
secreted by the pancreas to regulate blood sugar levels. Among the cells used for
digestion, are cells that produce hormones.
→ Alpha (α) cells secrete glucagon, which elevates the level of glucose in the
blood.
→ Beta (β) cells secrete insulin, which decreases the level of glucose.
In females, the important hormones are estrogen and progesterone. Both are
produced in the ovaries. They regulate the menstrual cycle and initiate production
of eggs.
Interstitial cells in the testes produce testosterone, which is the important sex
hormone in males. Testosterone is responsible for sperm production and
developing the secondary sexual traits.
Explain when and why hormones are
released.
Chemical compounds secreted by cells or glands that act on other cells or glands
in the body either locally or at distant sites (transported through the bloodstream).
They are released in response to a signal promoting growth, homeostasis,
reproduction, and regulation.
Define the different types of hormones.
Peptide/Amine Hormones
-
Due to their
hydrophilic
nature, they are unable to cross the cell's
hydrophobic plasma membrane. Therefore, they are only able to bind to
cell surface receptors. When binding to cell surface receptors, they
activate second messenger pathways through the cell, resulting in
changes in the metabolic state or gene expression of the target cell.
-
Peptide Hormones: type of hormone made from a chain of amino acids
Example(s): Oxytocin and ADH
-
Amine Hormones: type of hormone derived from a single aromatic amino
acid
Example(s): Epinephrine, Norepinephrine, and Dopamine are all
derived from the amino acid phenylalanine
Steroid Hormones
-
A type of hormone derived from cholesterol
-
Due to their
hydrophobic
nature, they are able to cross the cell's
hydrophobic plasma membrane. Inside the cell they bind to
nuclear/cytoplasmic receptors, causing them to act as transcription factors
which change the gene expression of the target cell.
-
Affect DNA transcription, more profound and long lasting effects
Discuss the role that hormones play in the
maintenance of homeostasis.
Changes in levels are detected and hormones are released/inhibited in response.
Send signals to stop the disturbance accordingly.
Provide examples of organisms that rely
on different modes of reproduction
r -strategies - lots of babies, not much parental care
K-strategies - few babies, lots of parental care
Internal fertilization - eggs fertilized inside body
Viviparity - Born alive (ex. humans)
Ovoviviparity - born as eggs and hatch (ex. shark)
External fertilization - eggs fertilized outside of body
Aquatic Environment - More likely to have external reproduction
Terrestrial Environment - More likely to have internal reproduction
Explain the relationship between the
hypothalamus and the pituitary.
Hypothalamus in the brain sends a message to the pituitary gland via neurons
and the pituitary gland secretes the appropriate hormone (LH, FSH).
→ The hypothalamus sends signals to the anterior pituitary gland through small
blood vessels. Neurosecretory neurons within the hypothalamus secrete
releasing factors into these blood vessels, which bind to cell receptors in the
anterior pituitary, signaling the release of hormones into the bloodstream.
→ The hypothalamus sends signals to the posterior pituitary directly;
neurosecretory cells whose cell bodies reside in the hypothalamus extend their
axons to the posterior pituitary. In response to action potentials, these cells
release hormones directly into the bloodstream that act on distant targets.
Determine whether a particular hormone
will interact with a cytosolic or
membrane-bound receptor.
Steroid hormones bind to a cytoplasmic receptor.
Thyroid hormones bind to a nuclear receptor (inside membrane)
Epinephrine binds to beta-adrenergic receptors on the plasma membrane of cells.
Predict which hormones have been
released from the pituitary to elicit a
specific tissue response.
LH and FSH
Usually hormones that go directly to another gland to produce an effect =>
master gland
Look at the target cell and response, should be opposite to the stimulus
Evaluate the consequences of altering a
component of a hormone pathway.
Make alternative then issue with feedback:
Thyroid => overproduction causes a goiter (enlarged thyroid gland)
Change set point => sensor affected
Don't respond to sensor => effector effected
Describe the processes of oogenesis and
spermatogenesis.
Oogenesis: happens when female is born
Oocytes matures in ovary → follicles grow and estrogen stimulates maturation
process → egg is released from follicle → follicle turns into corpus luteum in
ovary (releases progesterone) → egg travels to uterus → if egg is not fertilized,
corpus luteum degrades
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Spermatogenesis: happens continuously
Sperm generated in testes (seminiferous tubules) → passes through epididymis
(motility) → vas deferens → prostate (motility) → seminal vesicle (provides
nutrition) → bulbourethral gland (lubrication) → urethra → penis
Predict how changes in release of
pituitary sex hormones will alter
oogenesis and spermatogenesis.
There is negative feedback.
-
decrease testosterone leads to increases in FSH and LH
-
increase testosterone leads to decrease in FSH and LH
-
decrease in progesterone or estrogen then increase
-
increase progesterone or estrogen then decrease => use this for
contraceptives
The ovarian cycle is regulated via negative feedback between the ovaries and the
hypothalamus/anterior pituitary. Low levels of estrogen and progesterone
stimulate the initiation of a new ovarian cycle and follicular development.
Birth control pills maintain constant levels of estrogens and/or progesterone so
that the hypothalamus decreases release of GnRH blocking a surge in LH and
ovulation does not occur.
WEEK 4 LEARNING OBJECTIVES
Identify critical cells involved in auditory
and visual sensory transmission to the
brain.
Auditory
-
Hair cells: specialized mechanoreceptors that sense movement and
vibration.
-
Hair cells that detect sound vibrations are found in the cochlea and
those that are part of the vestibular system that sense gravity and
motion are found in the semicircular canals
-
Hair cells do not fire action potentials, but they release
neurotransmitters which affect the firing rate of adjacent neurons
when they’re depolarized.
-
Stereocilia: hair-like projections from the surface of the hair cell that move
in response to vibration.
-
Their motion causes depolarization of the cell's membrane by
opening or closing ion channels
-
Sterocilia cannot move on their own.
Visual
-
Opsin: light-sensitive protein that converts light energy into electrical
signals in receptor cell
-
They are G protein-coupled receptors, meaning they activate G
proteins which lead to a cellular response with Opsin, the cellular
response is a change in membrane potential.
-
Cone cells: photoreceptor cells that contains opsins sensitive to different
wavelengths of light
-
Provide the sharpest vision, color, found in fovea
-
Rod cells: sensitive to light but most sensitive to blue-green light (gray
shades) → found in periphery
-
Bipolar cells: receive input from rod and cone cells and releasing
neurotransmitters (do NOT fire action potentials)
-
Ganglion cells: located in front of the retina and receive input from bipolar
cells.
-
If activated, ganglion cells transmit action potentials by the optic
nerve to the visual cortex in the brain to begin processing images
Rods,Cones, and Bipolar cells generate graded potentials while ganglia cells
generate the action potentials.
Describe how hair cells function to
transduce mechanical signals to the brain.
Hair cells have stereocilia that project from the surface that move in response to
vibrations and cause an opening or closing of ion channels → ability to balance
and hear.
While they do not fire action potentials themselves, the depolarization causes a
release of neurotransmitters that alter the firing rate of adjacent neurons.
Sense of motion → the vestibular system is made up of two statocyst chambers
and three semicircular canals. Hair cells are located within the semicircular
canals and provide a sense of gravity and angular motion because as the head
rotates, the fluid in the canals causes the stereocilia to move and therefore
activate sensory neurons.
Ability to hear → hair cells affect our ability to hear by converting pressure waves
into an electrical impulse that is sent to the brain. Sound is received by outer ear
=> sent to eardrum => amplified by 3 middle ear bones (larger size of eardrum
compared to oval window)=> vibrations of oval window cause fluid pressure
waves in basilar membrane and cochlear duct => cochlear duct contains organ of
corti with stereocilia supported by the basilar membrane but projected into
tectorial membrane. Vibrations cause movement of the basilar membrane which
bends stereocilia because they are projected into unmoving tectorial membranes.
When stereocilia bend against the tectorial membrane it causes depolarization
and release of neurotransmitters. When stereocilia bend in the opposite direction,
hair cells repolarize and do not release neurotransmitters.
Describe parts of a simple reflex circuit.
(1) Particular tendon is activated (physician strikes tendon with hammer)
(2) Stretch receptors in extensor muscles respond by sending signals along the
sensory nerve.
(3) Sensory neuron synapses with motor neurons in the spinal cord.
(4) Motor neurons send excitatory signals to the same extensor muscle, which
responds by contracting.
(5) An inhibitory interneuron inhibits contraction of opposing flexor muscle
Need to inhibit others because muscles can only contract and not pull or push.
When one muscle is activated the other is inhibited → flexor stimulated, extensor
inhibited when bringing your hand/knee towards body, revered if bring away from
body
Goes from Afferent fiber (sensor) to spine (interneuron) inhibits extensor/inhibitor
efferent neuron and stimulates other extensor/inhibitor efferent neuron (motor
neuron) → cannot be activated at same time because do different actions in
same pathway
tetanus → This toxin is a poison that blocks the nerve signals from your spinal
cord to your muscles. This can lead to severe muscle spasms, muscle
contraction of sustained force
Predict how photoreceptors change in
response to light exposure.
In photoreceptors of the retina there are opsin molecules arranged in plasma
membranes that contain a light-absorbing pigment called retinal. When the retinal
absorbs a photon of light it undergoes a conformational change from cis-retinal to
trans-retinal. Rod and cone cells have leaky Na+ channels that let Na+ ions in
even at rest and release the neurotransmitter glutamate. However, when
cis-retinal changes to trans-retinal the Na+ channels close, causing the
membrane to become hyperpolarized and thus reduce the release of glutamate.
The reduction of glutamate triggers ESPNs and ISPN, affecting the firing rate of
neurons, which in turn provides information about location and intensity of light to
the brain. The photoreceptors synapse to bipolar cells, which receive their input
and, in response, also release neurotransmitters. The bipolar cells synapse to
ganglion cells, which activate and then transmit action potentials by the optic
nerve to the visual cortex
Rods and Cones - Hyperpolarize in response to light, but DO NOT fire action
potentials. Instead they synapse with bipolar cells which modulates their release
of neurotransmitters
Light <= Depolarize (ganglion cells) <= depolarize (bipolar cells) <= Hyperpolarize
(cones/rods)
No light <= Hyperpolarize (ganglion cells) <= Hyperpolarize (bipolar cells) <=
Depolarize (cones/rods)
Explain how sensory information is
encoded in action potentials.
The strength of a signal received by a sensory receptor neuron is indicated by the
rate that it fires action potentials.
For example, in the case of touch, stronger pressure results in higher firing rates
in the sensory receptor neuron. Over time, the receptor's rate of firing declines as
it becomes "familiar" with the signal. This process is known as accommodation.
The location of the signal's source is often determined using lateral inhibition. In
this case, pressure at one spot not only stimulates local sensory receptor neurons
but also inhibits adjacent interneurons. As the location of the stimulus changes,
the location with the strongest receptor signaling also shifts.
Lateral inhibition enhances the level of contrast between regions of receptors that
are being stimulated and surrounding regions that are not. Without lateral
inhibition the accuracy of locating the stimulus would be reduced.
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Explain how the processes of vision and
hearing occur.
Vision involves a complicated process of converting light signals into images in
the brain. Light passes through the lens, where it is focused, to the retina where
photoreceptors called rods and cones convert the information to electrical
impulses that can be interpreted by the brain. Rod/Cone cells detect light,
Rod/Cone cells stop sending neurotransmitters to bipolar cells, which in turn
begin to release neurotransmitters, causing ganglion cells to fire off action
potentials that signal the visual cortex in the brain. (as release of glutamate
closes the cation channel of bipolar cells, which causes it to become
hyperpolarized).
Sound (hearing), funnels into the ear canal and causes the eardrum to move.
Sound vibrations move through the ossicles to the cochlea. Sound vibrations
cause the fluid in the cochlea to move.The auditory nerve sends signals to the
brain where they are interpreted as sounds. Sound waves travel through the
auditory canal, eventually hitting the tympanic membrane. The membrane
vibrates, causing the 3 middle ear bones to vibrate. The last bone hits the oval
window that moves the fluid in the cochlea. The hair in the cochlea bend one way
or another depolarizing/hyperpolaizing and releasing neurotransmitters that
cause an action potential in later cells that send a signal to the auditory cortex.
Evaluate the molecular effect of a
stimulus on a sensory pathway.
A stimulus causes some sort of conformational change that allows
neurotransmitters to be released, usually turning the pathway on.
Predict how changes in a sensory
pathway will affect sensory perception.
If you affect one part of the pathway (cut off hearing nerve), anything that doesn't
allow the pathway to connect to the sensory nerve that sends signals to the brain
will cause there to be no perception of the stimulus.
Describe the structure and function of a
neuromuscular junction.
A neuromuscular junction is a synapse between a motor neuron and a muscle
where the neurotransmitter is acetylcholine. The function of acetylcholine is to
cause muscle contraction when activated.
**acetylcholine is found at the synapse.
-
Consists of a motor neuron synapsing with muscle fiber.
-
Various channels that open/close to let in certain ions.
-
Results in the release of neurotransmitters (ACh) that depolarize
muscles cells by opening Na+ channels and allows SrR to release
calcium, which binds to troponin and removes tropomyosin from
actin so myosin can undergo crossbridge cycle
1. Action potential reaches synaptic terminal → change in voltage
2. Voltage gated calcium channels open and calcium flows in
3. Calcium binds to vesicles with neurotransmitter acetylcholine, vesicles fuse
with membrane → exocytoses acetylcholine
4. Acetylcholine binds to the ligand-gated ion channels in muscle cell
5. Potassium flows out and sodium flows in → Na+ channels open =>
depolarization → action potential
6. Depolarization causes voltage-gated sodium channels to open
7. More sodium comes in
8. Action potential propagates down T-tubules → calcium released from
sarcoplasmic reticulum
9. SR release Ca2+, which bind to troponin in thin filament (actin), which moves
tropomyosin from the binding sites of myosin
10. Exposure of myosin-binding sites on actin allows cross-bridge as myosin
(thick filament) can now attach to produce shortening of muscle (contraction)
11. After AP, Ca2+ moves back to SR and tropomyosin covers actin again, after
contraction ends and muscle relaxes
Identify cellular, molecular, and protein
components involved in muscle
contraction and explain their role.
Muscle cell - cell that contracts
Motor cell - cell that relays signal to muscle cell to contract through the release of
acetylcholine
Actin filaments - (thin filaments) double helix that is encased by protein
tropomyosin
Myosin filaments - (thick filaments) myosin heads sticking out
Calcium - stored in sarcoplasmic reticulum, binds to troponin → change in shape
Troponin - bound to tropomyosin
Tropomyosin - wound around actin, blocking myosin binding sites
ATP - helps myosin head move and detach from actin
Action Potential in muscle - allows influx of Na+ions depolarizing the cell and
allowing opening of ca2+ channels
Muscle fiber - elongated cells that use ATP generated through ATP
Relate the structure of skeletal muscle to
its function in generating a contractile
force.
Larger muscles with more fibers produce greater forces
Muscle force is depending on the state already in.
-
Whole muscles are made of muscle fibers.
-
Muscle fibers use ATP.
-
Muscle fibers contain hundreds of long, rodlike structures called
myofibrils.
-
Myofibrils contain parallel arrays of actin and myosin filaments that cause
a muscle to contract
-
Sarcomere is found here.
-
Sarcomeres are arranged along the length of the myofibril.
-
The region from one Z disc to the next.
Actin subunits: thin filament (double helix with troponin and tropomyosin), lie
more on the outside of the sarcomere
Myosin: thick filament, lie in the center of the sarcomere
The thick and thin filaments slide with respect to one another, using ATP as a
source of energy. As a result of the sliding, the Z discs are pulled closer together
(shortening results from sliding of actin thin filaments relative to myosin thick
filaments) → causing contraction
The contraction of a whole muscle fiber results from the simultaneous contraction
of all of its sarcomeres → When Ca
2+
is present, this cycling of cross bridges
continues and the filaments continue to slide with respect to one another. When
Ca
2+
goes back into the sarcoplasmic reticulum, the contraction stops.
Striated muscles are arranged into muscle bundles.
-
muscle fibers (muscle cell) → myofibrils (rod-like structure that contains
parallel arrays of myosin and actin filaments)
Myofibrils have rows of actin and myosin that are broken up by z-discs in units
called sarcomeres.
Sliding Filament Model
Sarcomere length contracts when muscle contracts → more overlap of myosin
and actin filaments
When the muscle cell is depolarized, calcium leaves the sarcoplasmic reticulum
and binds troponin. This results in tropomyosin revealing the myosin binding sites
of actin filaments, thus allowing cross-bridge formation and muscle shortening.
Describe the cross-bridge cycle in a
skeletal muscle.
1. Myosin head binds ATP → binding of ATP allows myosin head to detach from
actin and readies it for attachment to actin
2. Myosin head catalyzes hydrolysis of ATP to ADP and Pi → results in
conformational change in which myosin head is cocked back. Because ADP and
Pi bound rather than released myosin head in high energy state => here is where
cycle is paused, myosin head not attached to actin
3. Myosin head binds actin, forming cross-bridge
4. When myosin head binds actin, myosin head releases ADP and Pi => results
in another conformational change in myosin head called power stroke => myosin
head pivots forward and generates force, causing myosin and actin filaments to
slide relative to each other => sarcomere shorten
Predict the effect of toxins or genetic
mutations on the function of skeletal
muscles.
cannot release ACh => no muscle contraction
no calcium => cannot send message so no contraction
receptor antagonist of ACh => no muscle contraction
Evaluate the physiological consequences
of altering the structure/function of
skeletal muscle components (e.g., SR,
myosin, troponin)
SR (sarcoplasmic reticulum) cannot release calcium → muscle cannot contract
because can't remove tropomyosin
Troponin cannot be bound to → muscle cannot contract
Myosin cannot unbind → muscle never relaxes
Compare and contrast the structure and
function of slow-twitch versus fast-twitch
muscles
The force exerted by a muscle depends on the frequency of stimulation by the
motor nerve → increase in frequency = summation → muscle force increases
Fast twitch muscle fibers:
-
produce a lot of force, gets fatigued easily- olympic sprinter
-
contract quickly and consume lots of ATP
-
Rely heavily on glycolysis to produce ATP
-
Less myoglobin => look white
The larger fast-twitch fibers take a shorter time to reach peak force and
can generate higher amounts of force than slow-twitch fibers. Fast-twitch fibers
can generate more force, but are quicker to fatigue when compared to slow-twitch
fibers.
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Slow twitch muscle fibers:
-
contract slowly and consume less ATP (greater resistance to fatigue) --
olympic marathoner
-
Have mitochondria to supply ATP to muscle fibers by aerobic respiration
-
Have a lot of myoglobin => look Red
-
Because they can provide their own source of energy, slow-twitch fibers
can sustain force for an extended period of time, but they are not able to
generate a significant amount of force.
-
Slow-twitch fibers have a low activation threshold, meaning they are the
first recruited when a muscle contracts. If they can't generate the amount
of force necessary for the specific activity, the fast-twitch muscle fibers are
engaged.
Ex: The tonic muscles responsible for maintaining posture have a higher density
of slow-twitch fibers. Steady-state endurance training can help increase
mitochondrial density, which improves the efficiency of how the body uses oxygen
to produce ATP
Tetanus == Muscle contraction of sustained force, calcium use does not increase
but is maintained at steady concentration
WEEK 5 LEARNING OBJECTIVES
Explain the relationship between surface
area-to-volume ratio and gas exchange
efficiency.
The rate of diffusion is directly proportional to the surface area over which
exchange occurs and to the concentration difference.
The rate of diffusion is inversely proportional to the distance over which the
molecules move.
Greater surface area to volume ratio→ easier to diffuse across membrane (rate of
diffusion is directly related to surface area), more efficient gas exchange
Describe the changes in muscle
contraction, volume, and pressure that
occur during ventilation.
Tidal Ventilation: air is drawn into lungs during inhalation and air is released from
lungs during exhalation
Inhalation: Diaphragm contracts (moves down)
-
thoracic cavity expands (volume expands/increases)→ air pressure in
lungs is less than outside of lungs → air is drawn in (inhalation)
-
negative pressure draws air into the lungs
-
More volume => less pressure
Exhalation: Diaphragm expands/relaxes (moves up)
-
thoracic cavity contracts (volume decreases) → air pressure in lungs is
higher than outside of lungs → air is pushed out
-
positive pressure forces air out of the lungs
-
Lower volume => high pressure
For relaxed breathing, the diaphragm controls the inhalation and the exhalation is
the product of elastic recoil of the lungs and chest wall.
Relate partial pressure and Boyle's Law to
ventilation and gas exchange.
Partial Pressure: fractional concentration of gas multiplied by the total
atmospheric pressure
(fractional concentration relative to other gases) X (atmospheric pressure)
Boyle's law: pressure of a gas increases, as volume of container decreases; the
pressure of a given mass of an ideal gas is inversely proportional to its volume at
a constant temperature
In lung:
Increase volume --> lower partial pressure (inhalation)
Decrease volume => increase partial pressure (exhalation)
Air pressure in lungs compared to air pressure outside of lungs determines
whether air is coming in or out → Gases always travel from an area of higher
partial pressure to an area of lower partial pressure
Reason why pO
2
changes as go up, the O
2
concentration is not changing, but the
atmospheric pressure is →
sea level => more pressure => so higher partial pressure
Higher elevation => less pressure => less partial pressure
Explain how the nervous system regulates
breathing and how this relates to
homeostasis.
Homeostatic Control of Breathing:
Oxygen and CO2 are homeostatically regulated.
Stimulus: O2 level decrease/fall and CO2 levels increase/rise
Sensors:
Chemoreceptors - (in brain) sense CO2 and H+ concentrations
Aortic bodies - (in heart in the aorta) sense O2 and H+ concentration in blood
going into the body
Carotid bodies - (in neck) sense O2 and H+ concentration in blood going to the
brain
Sensors detect decreases in O2 levels and increase CO2 levels.
Effector:
→ stimulate motor neurons
→ activate respiratory muscles and diaphragm to contract more strongly or more
frequently (stronger and faster breathing)
Response:
decreased levels of CO2
increased levels of O2 in blood
Most important factor in control of breathing is amount of CO2 in blood
Describe how hemoglobin binds oxygen
and how this relates to gas exchange.
Hemoglobin: protein in red blood cells that binds to oxygen
B/c oxygen becomes bound to hemoglobin, the pO2 in the red blood cell is lower
than the pO2 in the plasma, so O2 keeps diffusing into the cell.
As blood pO2 rises, O2 saturation of hemoglobin rises as well in a sigmoidal
fashion, b/c the binding affinity of hemoglobin increases as it binds more O2,
causing an increase in binding affinity with additional binding of O2.
Small increases in O2 lead to a large increase in hemoglobin oxygen saturation.
Right→ Low binding affinity means increased release of O2 into body tissue cells
=> increase dissociation => this also means that large amounts of O2 can be
released from hemoglobin when needed by cells
Left → Higher binding affinity => hold more O2 at lower pO2 => hard to
dissociate, because need a larger decrease in pO2 to release O2, why we use
hemoglobin instead
Saturation curve can move depending on pH, CO2 levels
Moves left if: lower CO2, higher pH, lower temp
Moves right if: higher CO2, lower pH, higher temp
Ex. The saturation curve is dependent on pH levels (Exercise → increased
aerobic respiration → increased CO2 from tissue → increased proton conc →
decreased pH → lower saturation levels (b/c more oxygen is delivered to cells)
Bohr effect: when pH falls (more H+ ions) during exercise => affinity of
hemoglobin for O2 decreases (moves right) => because binding affinity reduced,
more O2 released and supplied to cells for Aerobic ATP synthesis
This can also happen with an increase in CO2, which decreases pH and causes
hemoglobin to have lower binding affinity.
Water always has a slightly higher concentration of oxygen than the blood.
Evaluate oxygen-hemoglobin binding
graphs to predict the percent oxygen
saturation of different globin proteins
under varying conditions of PO2, pH, etc.
lower Ph = rightward shift → less binding affinity to release O2 more readily to
cells
higher CO2 = rightward shift
Leftward shift = Higher O2 affinity, lower CO2, higher pH, lower temperature
Rightward shift = Reduced O2 affinity, higher CO2, lower pH, higher temperature
Look at which part of the cycle they want you to find, look for the right pH (there
will be a decrease in pH due to heavy exercise => rightward shift), then use the
graph and pO2 given to O2 saturation)
Hemoglobin’s affinity for oxygen increases when proton concentration decreases.
Predict how changes in elevation or
external pressure will affect ventilation
and gas exchange.
Elevation results in thinner air → lower partial pressure → less oxygen attach to
hemoglobin
Higher external pressure (sea level) => more partial pressure, easier to breath
Less external pressure (elevation) => harder to breath
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There needs to be a balance.
Describe the properties of blood and
blood vessels.
BLOOD
Red blood cells (45%): transport oxygen and help transport carbon dioxide.
White blood cells (~1%): fight infection
Plasma (55%): water (solvent for carrying other substances), has ions for osmotic
balance and pH balance, and transport substances in blood
Blood travels through blood vessels.
BLOOD VESSELS
Arteries: transports blood away from the heart to the body or lungs (high pressure
and made of collagen and elastin to withstand high pressure => pulmonary artery
(towards heart from lung) and aortic valve (biggest artery, sends oxygenated
blood to body)
Arterioles: branches of arteries with smaller diameter
Capillaries: branches of arterioles with even smaller diameter (one red blood cell
thick) => where gasses are exchanged by diffusion with surrounding cells
Veins: transports blood toward the heart from the body or lungs (low pressure),
return blood towards the heart→ vena cavae (largest vein, drains blood from
body and head into heart), pulmonary vein (oxygenated blood from lung to heart)
Discuss the various functions of the cells,
proteins, and other components found in
human blood.
Composed primarily of Plasma and Cellular elements
Plasma is made of:
Water → solvent for carrying other substances
Ions (for cardiac action potentials, contractions, etc to be made possible).
Plasma Proteins (fibrinogen- clots, pH buffering, defense)
Substances transported by blood (hormones, nutrients, waste, O2 and CO2)
Cellular elements include:
red blood cells- transport oxygen and help transport CO2
Leukocytes(white blood cells)- help with defense and immunity
Platelets- assist in blood clotting.
Trace the flow of blood through the human
circulatory system.
1. deoxygenated blood enters the right atrium from the venae cava
2. deoxygenated blood passes right atrium → atrium contracts and blood moves
through atrioventricular (AV) valve into the right ventricle
3. right ventricle contracts, blood is pumped through the pulmonary valve to the
lungs for oxygenation
-
Right ventricle is thinner so it ejects blood at a lower pressure which
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allows blood of the pulmonary circulation to move at a lower rate allowing
more time for gas diffusion
4. oxygenated blood returns from the lungs through the pulmonary veins and
enters the left atrium of the heart
5. left atrium contracts, blood is pumped through a second atrioventricular valve
into the left ventricle
6. thick muscular walls of the left ventricle eject the blood through aortic valve
under high pressure to the body
Deoxygenated blood flows from the Body → Superior and Inferior Vena Cava →
Right Atrium → Right Ventricle → Pulmonary Artery → Lungs
Oxygenated blood flows from the Pulmonary Vein → Left Atrium → Left Ventricle
→ Aorta → Body
Describe the changes in blood pressure
and muscle contraction that occur during
the cardiac cycle.
Blood pressure goes from higher to lower pressure => "pressure gradient"
Muscle contraction → increases blood pressure
Muscle relaxation → decrease blood pressure
Diastole (ventricles are filling) is the relaxation of the ventricles - atria contract
and the ventricles fill with blood - ventricle pressure low
Systole (ventricles are emptying) is the contraction of the ventricles - blood is
pumped from the heart into the pulmonary and systemic circulations - ventricle
pressure high
During diastole => pressure in atria is high and low in ventricle
During systole => pressure in LV is high and low in the aorta
Relate changes in ion movement to the
cardiac action potential.
Longer than normal action potential
Sodium channels open → Sodium channels close → Calcium channels open and
fast potassium channels close → Calcium channels close and slow potassium
channels open → Resting potential → Fires again
1) Na+ is rushing into the cell to make the membrane potential more positive to
fire an action potential => depolarization (triggers contraction/systole of
ventricles)
2) The membrane decreases its permeability to the Na+ because the Na+
channels close.
3) On the plateau that corresponds to 2, the Ca+ channels open at the same time
as the K= channels close fast. This is the downtime that the ventricles needs to fill
with blood before contracting again (systole) => still depolarized
4) The Ca2+ channels are closing and the K+ channels are opening slowly which
causes a repolarization (membrane potential becoming more negative) =>
relaxation (diastole)
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5) Resting membrane potential (k+ ions are leaving)
Explain heart muscle contraction in
response to an action potential.
Ions flow into the SA node → action potential fired → atria contract
Ions flow into AV node → action potential → travels to Bundle of His → Purkinje
fibers → ventricles contract
Relate the events during the cardiac cycle
to those represented on an ECG.
Depolarization= Contraction
Repolarization= Relaxation
At P: SA node activated → action potential fires → atria (depolarization) contracts
→ atria empties → ventricles fill (actively)
Before QRS (delay): The delay in transmission from the AV node and through the
conducting fibers ensures that the ventricles do not contract until they are fully
filled with blood from the atria.
AV node activated → fires action potential → travels to Bundle of His and
Purkinje fibers (takes time)
QRS: Atria repolarize + relax + refill and Ventricles (depolarize) contract →
Ventricles empty. Depolarization of the ventricles- ejection of the blood from the
heart and into the arteries - beginning of the systole - first heart sound -
repolarization of the atria
ST segment: where ventricular repolarization begins, atria are filling again,
maintain contraction of to make sure all blood in ventricles expelled
T: Ventricles relax and fill (passively, b/c of gravity). Ventricles repolarize and
relax - repolarization of AV node
Systole lasts until the T wave!!! (Ventricles are still emptying)
WEEK 6 LEARNING OBJECTIVES
Define the terms osmolarity, tonicity,
hypertonic, hypotonic, and isotonic.
Osmolarity: concentration of solute compared to the total amount of solute
-
lower osmolarity = less solutes
-
higher osmolarity = more solutes
Osmosis: movement of water from lower to high solute concentration
Tonicity: state of solution in terms of osmotic pressure
Hypertonic: higher solute concentration and lower water concentration (than
another solution) ==> water will flow in
Hypotonic: lower solute concentration and higher water concentration (than
another solution) => water move out
Isotonic - same solute concentration and water concentration (as another
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solution) => no net flow of water
Compare and contrast different forms of
nitrogenous waste and their effect on
osmotic balance.
Ammonia
-
produced by the breakdown of proteins
-
contributes to osmolarity
-
water soluble
-
Fish able to excrete ammonia directly into water through gills by simple
diffusion=> process not energetically expensive
-
Most toxic
-
need lots of water to dilute toxin
Urea
-
Mammals, many amphibians, sharks, and some bony fish excrete
nitrogenous waste in this form
-
In mammals produced in liver, carried to kidneys via blood where it is
eliminated
-
Contributes to osmolarity
-
Less toxic than ammonia but takes more energy to make and water to
excrete
-
Need energy to convert and to release concentrated urea in water
-
Water soluble
Uric Acid
-
Least toxic
-
Birds, reptiles and many arthropods
-
Most energy lost and most energetically expensive
-
Not dissolved in water (not water soluble), it does not exert osmotic
pressure and is eliminated with minimal water loss
Explain what is meant by the phrase
counter-current multiplier.
Generates concentration gradients instead of maintaining them like
countercurrent exchange.
A system that generates a concentration gradient as two fluids move in parallel
but opposite directions.
Ex. Loop of Henle
-
actively transporting solute (electrolytes) out of the ascending limb and
allowing water to diffuse out of the ascending limb (filtrate enters and
leaves loop with same concentration)
-
allows water to be reabsorbed by the blood from the descending limb
Describe the structure and function of the
mammalian kidney.
The cells of the kidneys are surrounded by a solution called the interstitial fluid.
Functional unit of the kidney is the nephron.
Concentration of solutes increases as you move down => most concentrated
interstitial fluid at base of kidney.
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Filtrate - fluid inside of nephron.
The glomerulus is a tuft of capillaries that filters the waste in the blood to make
the filtrate (where filtration occurs)
Proximal convoluted tubule - the first portion of the renal tubule from which
electrolytes and other nutrients are reabsorbed into the blood => reabsorbs all the
glucose and amino acids filtered by the glomerulus, as well as most sodium and
chloride ions (Reabsorption)
Loop of Henle - the middle portion of the vertebrate renal tubule, which creates a
concentration gradient that allows water passing through the collecting duct to be
reabsorbed (Reabsorption)
Distal convoluted tubule - the third portion of the renal tubule, in which urea is the
principal solute and into which other wastes from the bloodstream are secreted
(Secretion => active process) => (change blood pressure (increase salt and water
retention)
Collecting duct - where water levels are adjusted to meet the osmoregulatory
needs of the organism and therefore maintain homeostasis (can be permeable to
water depending on ADH**)
**ADH= antidiuretic hormone → a hormone that helps blood vessels constrict and
helps the kidneys control the amount of water and salt in the body.
Relate water and ion movement through
the nephron.
Water movement → passive transport through the nephron, it is usually excreted
back into functioning tissue
Ion movement = active transport
Water usually moves by osmosis (passive) in the descending limb of loop of
Henle (could be on the line down (collecting duct) if increase ADH)
Ions/waste/nutrients → move through active transport at proximal convoluted
tubule, descending limb, and distal convoluted tube
Differentiate between passive and active
transport as filtrate moves through the
nephron.
Water usually moves by osmosis (passive) in the descending limb of the loop of
Henle (could be on the line down (collecting duct) if increase ADH) => water
moves down concentration gradient due to concentration gradient made by loop
of Henle.
Ions/waste/nutrients => move through active transport at proximal convoluted
tubule, descending limb, and distal convoluted tube => active transport move
against concentration gradient and need ATP => most active transport when
things are being reabsorbed.
Relate water balance and kidney function
to changes in blood pressure.
Overhydrated/decrease in blood osmolarity → hypothalamus solute concentration
low → no ADH (vasopressin) released → collecting duct is not permeable to
water → water stays in urine → large volume of diluted urine and decreased
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blood pressure
Dehydrated/increase in blood osmolarity→ Hypothalamus sense solute
concentration high → releases ADH (vasopressin) → increased permeability of
collecting duct to water → water reabsorbed into blood → small volume of
concentrated urine and increased blood pressure
Low blood pressure (low Na+) → kidneys secrete renin → angiotensin to
angiotensin I → (in lungs) angiotensin I to angiotensin II → hormone causes
arterioles through body to constrict and direct blood back to heart => adrenal
cortex secretes Aldosterone → distal convoluted tubule increases reabsorption of
sodium and water into the blood → increases blood volume → increases blood
pressure
Too much Na+ in blood → reduces the ability of your kidneys to remove water.
This will result in a higher blood pressure.
High blood pressure (high Na+) → heart secretes ADH → ANP secretion → distal
tubule takes up more sodium and water → decreases blood volume → decreases
blood pressure
increase blood volume → increase BP
decrease blood volume → decrease BP
Predict how altering osmolarity or
membrane permeability in the nephron
will affect kidney function.
Lowered osmolarity (decrease ADH) causes Na+ and Cl+ reabsorption in the
kidneys and less concentrated urine => increase in urine => more dilute urine
Increased osmolarity causes increased levels of ADH. This will add aquaporin
channels that allow more water to be reabsorbed. This causes the concentration
of urine.
Loop of Henle dependent on membrane permeability
Evaluate the effect of hormones (e.g.,
ADH and aldosterone) and drugs on the
function of the kidney.
Increase ADH (dehydrated)/ high osmolarity => more permeable to water =>
concentrated urine
Less ADH (well-hydrated)/ low osmolarity => less permeable => dilute urine
Diuretic (alcohol) => decrease ADH => promote urine dilution => net loss of water
=> dehydrated
Aldosterone => secreted by adrenal gland, increases blood pressure by
increasing blood volume, increase salt and water uptake by distal convoluted
tubule
If aldosterone levels decrease the reabsorption of electrolytes and water back
into the blood decreases and therefore blood pressure will decrease
Predict how water will move if the
osmolarity of cells or body fluids is
High osmolarity= decrease in water concentration. This means that the kidneys
will want to increase the amount of reabsorption of water to prevent dehydration.
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altered.
This means that the water will passively diffuse out of the loop of Henle. Urine
becomes more concentrated at higher osmolarities because water is moving out.
Increase/high osmolarity => water move down concentration gradient, increase
ADH
Low osmolarity= increase in water concentration. This means the H
2
0 will want to
be secreted so that there isn't overhydration. (ex. The ascending loop of henle is
not permeable to water because it has decreasing amounts of osmolarity. It is
during that time that Na and Cl are being reabsorbed.When Na and Cl are being
reabsorbed, the urine becomes less concentrated. This part of the loop of henle
is not permeable to water so only Na and Cl can be reabsorbed.
Low osmolarity => water dilution, decrease ADH
Relate food consumption to energy
acquisition.
Need to eat food in order to get energy and nutrients our body cannot make
(cannot be synthesized by the body) => "essential" amino acids and minerals
Describe the process of digestion as food
moves through the stomach, duodenum,
and small intestine.
Mouth
- Mechanical and start of chemical breakdown
- food mixed with amylase - enzyme that breaks down carbohydrates and lipase
which breaks down lipids => works at a neutral pH
Stomach
- main sites of protein and lipid breakdown
- largely protein breakdown
- gastric hormone stimulate secretion of gastric juices => lower pH
- Chief cells secrete pepsinogen (in its inactive form it is secreted so it does not
digest itself) => activated to pepsin by low pH made by HCl-> made by low pH by
parietal cells making HCl (hydrochloric acid) - these two come together to make
active pepsin which breaks down proteins into amino acids
- Made acidic by break down of CO2 and H2O into protons that move across
membrane by K+/H+ ATPase and Cl- goes straight across both membranes to
make HCl
Small intestine
- Digestion of protein, fats, and carbohydrates in duodenum (first part of small
intestine) and absorption of nutrients
- Duodenum increases release of secretin which makes pancreas release
bicarbonate which neutralizes pH
- Pancreas also produces: Lipase - break down fats, Amylase - breaks down
carbohydrates, Trypsin - breaks down proteins
- Fats in duodenum stimulate release of CCK which stimulates gallbladder to
produce bile that emulsifies fats - breaks down large clusters of fat into smaller
lipid droplets
- Jejunum and ileum - rest of small intestine where absorption takes place -
absorbed across microvilli surfaces
- more neutral pH => so enzymes from mouth renature
Large intestine
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- Water and inorganic ions absorbed
Discuss the role of enzymes and other
secreted molecules throughout the
process of digestion.
Fats in the duodenum secrete CCK which makes the gallbladder release Bile to
break down fats
Stomach acid in the duodenum secretes secretin which influences the pancreas
to secrete bicarbonate to neutralize it
Gastrin is secreted to stimulate secretion of gastric juices => lower pH
Amylase: breaks down carbohydrates => found at neutral pH => found in mouth
and small intestine (amylase produced by pancreas)
Lipase: breaks down fats/lipids => mouth (tongue lipase), stomach lipase, and
small intestine (pancreatic lipase)
Pepsin: breaks down protein => works at low pH (made by hydrochloric acid and
gastrin) => found in stomach were most protein breakdown occurs
Trypsin: enzyme produced by pancreas that breaks down proteins
Secretin: hormone released by cells lining duodenum in response to acidic pH of
stomach contents entering small intestine and stimulates pancreas to secrete
bicarbonate ions
bile: produced by liver and stored in gallbladder, aid in fat digestion by breaking
large clusters of fats into smaller lipid droplets
CCK: peptide hormone senses fat content and causes gallbladder to contract =>
releasing bile into duodenum
Describe how and where different
nutrients are absorbed.
Nutrients => glucose, protein, and lipids absorbed in small intestine and water
and inorganic ions in large intestine
- because products of fat digestion are lipid soluble they do not require a carrier
protein for transport => readily diffuse from lumen into cells
glucose and protein enter lumen of small intestine and use co-transporters driven
by Na+ going down its concentration gradient => Na+ concentration is kept low
inside the cell by action of the Na+-K+ pump
Glucose exists the intestinal cell passively by a glucose transport protein
Evaluate how changes in cellular
physiology (i.e. altering transporters or
cell-cell adhesions) could affect nutrient
absorption.
If you break concentration gradient then things will not flow/travel the right way
Break Na+/K+ => then no Na+ gradient, so can't break glucose and protein into
cell
Break cell-to-cell junction => then no impermeable layer and Na+ will go straight
through with no regulation
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No ATP => Na+/K+ transport cannot work => no gradient
Explain the role of hormones in regulating
the digestive system.
Fats in the duodenum secrete CCK which makes the gallbladder release Bile to
break down fats
Stomach acid in the duodenum secretes secretin which influences the pancreas
to secrete bicarbonate to neutralize it
Predict how altering the release of
hormones or digestive enzymes will affect
digestive processes such as the
breakdown and absorption of nutrients.
If secretin not released => very acidic in duodenum from stomach and enzymes
cannot work
If bile not released because does not release CCK => cannot break down fats
No gastrin => cannot make pH in stomach lower for peptide to work
pH might be too low or high restricting enzymes from working
Relate the processes of digestion, nutrient
absorption, and energy acquisition to
homeostasis.
Nutrient absorption => not homeostatic, just absorbs everything
H+ (pH concentration) => homeostatically regulated, use secretin => in diagram it
is response that is being regulated
Gastrin => make pH lower => homeostatic
CCK in response to fat => homeostatic
WEEK 7 LEARNING OBJECTIVES
Define and differentiate between the
terms microbiome, microbiota,
metagenome, and holobiont.
Microbiome - Entire habitat of microbes, their genomes, and their surrounding
environment.
Microbiota - bacteria that inhabit a particular environment => referring to microbes
themselves, the identity of the microbes => use 16S rRNA gene sequencing to
find specific bacteria.
Metagenome - collection of genes and genomes that form a microbial community.
Holobiont - An organism and all of its symbiotic microorganisms. Host and all its
symbiotic bacteria.
Explain how and when the human
microbiome is formed.
Human microbiome is formed when we are born
-
human microbe is formed during birth during the birthing process, first
contact with the mother
-
microbes look most similar to mothers microbes
-
sterile womb (so birthing canal = first environment w/microbes)
-
Babies born vaginally have microbiome more similar to mother's vaginal
microbiome
-
Babies born with c-section have a microbiome more similar to mother's
skin microbiome
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Describe how major life events influence
the microbiome
Depending on dietary introductions, the abundance of each bacteria may change
over time.
Breast feeding
-
early microbiota is milk oriented (have lactose, lipids, and protein digestive
enzymes => HMOs (human milk oligosaccharides)
-
human milk has oligosaccharides and only bifidobacterium can digest
them (broken down extracellularly), not the host => microbes only carry
enzymes able to digest HMOs.
High-fiber diet
-
non-digestible carbohydrates (bacteria can only digest them, not host, and
turn them into short chain fatty acids) => bacteroides help digest
non-digestible fibers and are specific to certain sugars => use specificity
of food preferences to enrich for particular species over others
-
food diet changes microbiome
Identify selective pressures present in the
developing and adult microbiome.
Stability - ability to resist change (resistance to shifting environmental conditions)
and protection against exogenous microbes/pathogens.
Indirect colonization resistance: microbes signal to immune system, leading host
production of antimicrobial peptides, antibodies, mucous
Resilience - ability to return to original state following perturbations => bounce
back to original state very quickly
Antibiotics kill off disease microbes, but also normal microbes. Not perfect
recovery, even though there is some recovery, microbiome does not look the
same after antibiotic treatment.
Presence of normal microbiota important for defending against infectious
diseases => antibiotics can kill these good bacteria, which can cause colonization
resistance to be breached, and cause microbiota shifts (CDI)
Explain in general terms how 16S rDNA
sequencing data is collected.
16S rDNA: helps us study what microbes are present in a microbiota sample by
identifying microbes based on genetic sequences
1. Take DNA from Biospecimens (e.g. stool, skin, lungs, reproductive tract)
2. Sequence genes for 16S rRNA gene
3. Allows identify all microbes present in a sample => then, use reference
database to get identification number for each of bacterial species
-
use identify number (microbe ID => OTU) or can use reference database
to see how related microbes are to each other
Differentiate between alpha diversity and
beta diversity.
Alpha diversity: quantitative measure of different microbes present in a sample
-
graph uses OTUs on its y-axis, tells you how many unique species of
bacteria there are and what species they are in one unique sample
Beta diversity: multiple samples, looking at similarities in function (PCA2),
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relatedness of certain microbes
-
each dot represents a sample
-
use PC2 and PC1 (Principle Coordinate Analysis (PCoA): Method to
visualize similarities versus differences between large datasets from
multiple samples, all different raw values of OTUs that cluster similar to
each other)
Beta diversity can also be used to show abundance of certain phyla (different
bacteria) in relation to different body parts.
Interpret 16S rRNA gene sequencing
data.
Use 16S rRNA sequencing data to find:
1. Genetic relatedness, sequence similarity, measure variation between samples.
Compare the sequences to a database of known bacterial sequences (beta) =>
or can use it to take data from different parts of the body and look at phyla,
abundance of particular phyla of microbes in certain body habitats
2. Find microbe's ID, OTU, Determine bacterial species and quantity of each
species (Alpha)
- can use 16S rRNA to find specific taxa of microbes
- Abundance of microbial genes (shows metabolic pathways) does not use 16S
rRNA sequencing, because need to use the whole genome to find all microbial
pathway, all of these enzymes not coded for in 16S rRNA, but in the rest of the
genome
Interpret data relating to microbe-microbe
and microbiota-host interactions.
Microbe-microbe: coexist or can take over causing the other microbe to no longer
survive (i.e vibrio takes over and does not allow Aer to survive in gut)
Microbiota-host: microbes allow host to digest food that host cannot, or can take
over host actions
(i.e. vibrio causes smooth muscle to contract, which makes host cause Aer to be
excluded it through intestinal interactions)
Describe ways in which the host can alter
the microbiota and vice versa.
Host: If the host takes antibiotics, develops a new diet, the microbiota in the gut
could be altered, or can come in contact with, ingest, microbes.
Microbiota: Allows host to digest food if host cannot or microbiota can take over
host systems (i.e vibrio makes smooth muscle contract)
Discuss what constitutes a "healthy"
microbiome.
- high resilient microbes
- high biodiversity (allows for more extraction of nutrients)
Define pathogens.
organisms and other agents, such as viruses, that cause disease
Differentiate between adaptive and innate
immunity.
Adaptive (acquired) immunity: specific to given pathogen (B and T cells),
"remembers" past infections (meaning subsequent encounters with same
pathogen generate stronger response), adapts over time and is acquired after
initial exposure.
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Innate (natural) immunity: provides protection against all types of infection in a
nonspecific manner; does not depend on prior exposure to pathogens.
Explain the ability of the innate immune
system to combat a variety of pathogens.
First line defense: skin and mucous membranes
-
mucous membranes of respiratory and GI tract acts as physical barriers
Second line of defense: WBC of the innate immune system
-
phagocytes engulf and destroy foreign cells or particles by phagocytosis
-
mast cells release histamine an important contributor to allergic reactions
and inflammation
Complement system: certain proteins circulating the blood participate in innate
immune function and thus complement parts of the immune system => activation
has 3 effect (activated by proteins/antibodies attach to antigens): cell lysing,
phagocytosis, and inflammation
Describe inflammation and why this is
sometimes observed with injury.
Inflammation is caused by mast cells that release histamine.
1. Bacteria and other pathogens enter a wound.
2. Mast cells release histamine that increases blood flow (causing redness and
heat) and makes blood vessels leaky (causes swelling)
-
histamine acts directly on blood vessels causing vasodilation, increasing
blood flow to the site of infection or injury
-
histamine causes fluid to leak out of the blood vessel, carrying white blood
cells into the damaged tissue.
-
the increased fluid in the tissue surrounding the blood vessels is
visible as swelling
3. Immune system cells (such as dendrite and mast cells) recognize pathogens
as foreign and release cytokines that bind to and recruit phagocytes in nearby
blood vessels.
4. Phagocytes enter infected sites from blood and remove pathogens by
phagocytosis.
Relate exposure to pathogens to
triggering the adaptive immune system for
B-cell development.
B CELLS PRODUCE ANTIBODIES.
T CELLS KILL OFF BODY'S OWN CELLS THAT HAVE BEEN TAKEN OVER BY
VIRUSES.
Clonal selection: process by which antigen binding generates a clone of B cells
-
clonal selection resembles natural selection => there is variation in a
population of B cells, and the antigen selects among this variation,
allowing some cells to proliferate more than others
1. Population of B cells: B cells express a diversity of dell-surface antibodies
2. Selection: A foreign antigen interacts with one B cell from the population. The
B cell divides to form a population of clones
3. Differentiation: The B-cell clones differentiate into plasma cells that secrete
antibodies and memory cells with cell-surface antibodies
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Compare and contrast what happens
during primary and secondary immune
responses.
Primary Immune Response: immune system has to learn to recognize antigen
and how to make antibody against it and eventually produce memory
lymphocytes => lag time, short lag before antibody is produced
Secondary Immune Response: memory cells remember antigen and the immune
system can start making antibodies immediately
The response to re-exposure to an antigen, which is quicker, stronger, and longer
than the primary response => produces more antibody than primary exposure
and has longer duration
Evaluate the effect of immunizations on
immune system development.
Immunizations → creation of memory cells → better at recognizing and getting rid
of pathogens
Vaccines are made from dead or weakened antigens => Immune system
produces antibodies and memory cells in response
-
allows for quicker response if subject is infected by actual disease
The deliberate delivery in a vaccine of an antigen from a pathogen to induce a
primary response but not the disease, thereby providing future protection from
infection.
Describe the structure and function of an
antibody.
A large protein produced by plasma cells that binds to molecules called antigens
=> large protein found on the surface of B cells or free in the blood or tissues =>
binds to pathogen to target them for destruction
Explain how the process of VDJ
recombination leads to the production of a
diverse set of antibodies.
Allows there to be various different genetic combinations for antibodies, allows
antibodies to diversify, it is how B cells make different kinds of antibodies
VDJ recombination→ how B cells make different kinds of antibodies.
Describe in general terms how the gut
microbiome contributes to immune system
health.
The gut microbiome makes it hard for foreign pathogens to colonize.
Indirect colonization resistance: microbes signal to immune system, leading host
production of antimicrobial peptides, antibodies, mucous
Microbiota protect against opportunistic bacteria, however antibiotics can kill of
this good bacteria
Colonization resistance: microbiota fill up the entire dense space, protect against
disease by filling up the physical space, so that new pathogens causing microbes
are going to have a difficult time finding space to colonize persistently. Also, they
utilize the nutrients very efficiently, so that the nutrients will be hard to utilize for
any exogenous disease causing microbes => all help to resist invasion by
disease causing pathogens
Predict the type of immune response a
particular pathogen would likely elicit.
If it is a cancer cell or a cell that has been damaged by a virus or pathogen =>
Cytotoxic cells will be used to kill the host cell
If penetrates through skin and mucous => use second line of defense =>
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inflammation (mast cells) and phagocytosis
White blood cells of innate immune system => mount an early response to a
pathogen, if they are unable to clear the pathogen, they alert the more
specialized white blood cells of the adaptive immune system (B cells)
WEEK 8 LEARNING OBJECTIVES
Define the terms genome, genome
sequencing, sequence assembly, and
genome annotation.
Genome: DNA molecules that are transmitted from parent to offspring.
Genome sequencing: figuring out the order of DNA nucleotides in a genome.
Sequence assembly: putting fragments of DNA sequences into the correct order
to recreate entire genome
Genome annotation: process by which researchers identify various types of
sequences present in the genome
Describe the process of sequencing used
to generate genome sequences.
1) Fragment DNA → first break long string of DNA into smaller pieces
2) Add adapters to end of all DNA → important because we can add the same
nucleotide sequence to the end of every fragment means that the same primers
can be used to sequence all of the genome fragments
3) Denature fragments (each piece is separated) and are attached to a solid
surface
4) Each fragment is copied (amplified) to make thousands of copies of each
genomic piece → cluster of identical DNA fragments
5. Each DNA fragment is used as a template to synthesize the complementary
strand. Each new nucleotide that is added has a fluorescent molecule attached,
so A, T, C, and G show up as different colors under a microscope.
6. Then, short sequences are put together in the correct order to generate long
continuous sequences of nucleotides in DNA molecules.
→ assembly accomplished according to their overlaps (shot gun sequencing)
Differentiate between small-scale and
large-scale genome mutations.
SMALL SCALE
1)
Point mutations: mutation in which one base pair is replaced by a different
base pair
2)
Missense mutation: point mutation (nucleotide substitution) that causes an
amino acid replacement
→ can affect three-dimensional structure of protein and therefore change
its ability to function
3)
Silent mutation: mutation resulting in codon that does not alter
corresponding amino acid in polypeptide => no change in function, usually
at 3' end of codon (third position)
4)
Nonsense mutation: mutation creates stop codon, terminating translation
→ truncated nearly always nonfunctional, unstable and quickly destroyed
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5)
Frameshift: Mutation in which insertion or deletion of some number of
nucleotides that is not multiple of 3, causes shift in reading frame of
mRNA, changing following codons
→ all amino acids downstream, of site of insertion/deletion are changed.
resulting in loss of protein function
LARGE SCALE MUTATIONS
1)
Duplication: region of chromosome that is present twice instead of once,
less harmful when smaller rather than large, less harmful than deletions
2)
Deletion: Region of chromosome is missing resulting from error in
replication from joining breaks in chromosome that occur on either side of
deleted region
3)
Inversion: The reversal of the normal order of a block of genes, produced
when region between two breaks in chromosome is flipped in orientation
before beaks are repaired
4)
Translocation: Interchange of parts between nonhomologous
chromosomes. When two different (nonhomologous) chromosomes
undergo exchange of parts. Both chromosomes are broken and terminal
segments are exchanged before breaks are repaired
Describe how genomics can be used in
cancer research.
We can see if cancers are associated with common mutations. This can lead to
discovering the possibility of correlations between those mutations and the
development of cancer => can allow us to understand which genes affect cancer.
Assemble sequencing read data based on
a reference genome.
Can map onto the mapping (template) or complementary strand (coding,
nontemplate) strand => need to match up the overlaps to the reference genome
We can detect mutations => by comparing sequence read differences from
reference sequence, get sequencing reads from cancer and healthy cells and find
the ratio between them.
Evaluate data from short-read based
genome-wide measurements to detect
small-scale and large-scale genome
mutations.
WHAT WILL BE DEPICTED ON GRAPHS FOR DIFF
Small-scale → shows one nucleotide or few changes, on DNA sequence level,
use data with dots (goes from 5' to 3' end), compare new sequence read to
reference genome, look at graph and determine y-axis, tells you where mutations
occur
Large-scale → on chromosomal level, show karyotype, use circle diagrams
Interpret circle diagrams of DNA
sequence data.
Circle plots show changes in cancer genomes vs. the reference genome
Circle plots do NOT show small scale mutations, need sequencing reads to find
this.
Look at large scale (chromosomal level) mutations of tumor samples
WEEK 9 LEARNING OBJECTIVES
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Identify elements of protein-coding genes.
Translated by Exons, only make up about 2% of the genome
Long DNA codes for proteins or RNA molecules with specialized functions
Protein codon regions have long open reading frames
transcription factors - turn genes on or off by binding to nearby DNA
- activators => promoters and enhancers turn on gene, positive regulation
- repressors => turn off gene expression, negative regulation
RNA polymerase - binds promoter to start transcription
-
reads from '3->5' and creates from 5'->3'
For proteins, 5' end has NH2 and 3' end has COOH (ie. NH2-Met-
......
-AA-COOH)
Interpret genome browser profiles
summarizing data for coding and
non-coding positions in a genome.
Can look at acetylation:
If high acetylation in intron (non-coding region), then probably an
enhancer/repressor (regulatory sequence), especially if conserved
If high with gene → promoter/terminator region
If high at all → biochemical evidence of importance
Can look at conservation:
If conserved w/o gene → probably a regulatory region
If conserved w/ gene → probably a gene that produces a protein that is important
for healthy living → evolutionary evidence
Can also see if we can use model species to use to understand effects of gene
=> want one that has gene looking for highly conserved
Can look at actual protein expressed → genetic evidence (not shown in genome
browser, need to be given information separately)
Check diagram in notes as well for more information on how to interpret genome
browser.
Describe how properties of particular
amino acids in a protein may affect
protein structure and function.
Some amino acids are polar, nonpolar, basic, acidic, etc, which would affect
structure and function.
Changing these amino acids could seriously disrupt function, especially if the new
amino acid has very different properties.
Transmembrane protein should be non-polar, but if mutation causes it to change
polarity would not be able to function → loss of function
Evaluate the effect of a coding mutation.
Mutation within coding regions is rare, mostly occur in non coding regions,
however could cause issues as noncoding regions can code for regulatory
mechanisms.
In coding regions can cause amplification/overexpression of the gene => can
cause proliferation of cells that cause cancer
Coding mutation can cause protein to no longer be functional => loss of function
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or cause it to be overexpressed => cancer
Explain the role of model organisms in
research.
Want to pick one that has high conservation of the region that you want to study
=> usually mice
Select an appropriate model organism to
address a given research question.
Yeast => unicellular organisms, good if want to see one cell mechanism, but not
cell to cell contact
Mice => usually have conserved/closely related biological processes to humans
Compare and contrast evolutionary,
biochemical, and genetic approaches in
determining functional elements in
genomes.
Biochemical approach: measures evidence for molecular activity
→ on genome browser: look at H3K27 acetylation
Evolutionary approach: quantifies selective constraint as a proxy for functionality.
→ comparing conservation tracks in the genome
Genetic approach: evaluates the phenotypic consequence of genome variations.
→ consequence of genome variations
Formulate a hypothesis to address the
likely function of a mutation in the cancer
genome taking available genomic
information into consideration (week 10
discussion)
Loss of function for tumor suppressor → proliferation
Loss of function in promoter/enhancer → repressed
Loss of function in repressor → proliferation
Gain of function in repressor → repressed
Gain of function for proto-oncogene → proliferation
Gain of function in promoter/enhancer → proliferation
Define DNA/gene editing.
techniques that allow researchers to "rewrite" the nucleotide sequence of DNA so
that specific mutations can be introduced into genes
Describe the structure and function of the
CRISPR/Cas9 system and its application
to human gene editing.
Cas9 is a protein that binds to a single-guide RNA (sgRNA), once bound the
complex searches for a PAM sequence (5'-NGG), once it finds a PAM sequence,
it binds to the opposite strand that the PAM sequence is on and if the single-guide
RNA can hybridize, it does, and then Cas9 cuts the DNA (both strands) 3
nucleotides downstream from the N.
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sgRNA + Cas9
1. Cas9 and sgRNA bind
2. Cas9/sgRNA complex scans DNA for PAM sequence (5' NGG)
3. Cas9 unwinds DNA near PAM
4. sgRNA hybridizes with DNA
5. Cas9 cuts target DNA 3 nucleotides upstream of PAM
6. Attempted repair
sgRNA:
- Scaffold region: part that binds to Cas9
- Spacer region: sequence complementary to target sequence, hybridizes target
DNA
Identify how RNA complexes interact with
complementary sequences.
hybridize
WEEK 10 LEARNING OBJECTIVES
Explain how double-strand DNA breaks
are repaired (non-homologous end joining
and homologous recombination).
DNA REPAIR OCCURS BY:
Non-Homologous End Joining (NHEJ)
- DNA is broken, the single strand tails
are removed and then ligase stitches the remaining ends back together =>
make/introduce mutation, deletions/insertion can cause frameshift mutations that
shift ORF and cause protein to become nonfunctional, disrupt gene=> knockout
Very imprecise, generally lose lots of nucleotides
Good for BIG changes (large insertion or gene, translocation, etc)
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Homology Directed Repair (HR)
- DNA is broken, single stranded tails find
homologous DNA and use that as a template to recreate missing nucleotides →
other single stranded tail uses newly synthesized nucleotides as a template
strand → double strand back together => trick cell into using donor template by
using same flanking regions, precise editing, can change sequence of genome
(knockin)
Much more precise
Good for small mutations!
Distinguish between the terms: tumor and
metastatic cancer.
Tumor: a tumor can be benign or malignant. Benign tumors are growths that are
not cancer. It does not invade nearby tissue or spread to other parts of the body.
Metastatic cancer: malignant tumors have cells that grow uncontrollably and
spread locally and/or to distant sites. Malignant tumors are cancerous (ie, they
invade other sites). They spread to distant sites via the bloodstream or the
lymphatic system. This spread is called metastasis.
Explain how oncogenes and tumor
suppressor genes can lead to the
development of cancer.
Oncogenes are the main genes contributing to the conversion of normal cells to
cancer cells and tumor-suppressive genes block the development of cancer. The
way they both act is complicated and needs further investigation to fully elucidate
cancer pathways and carcinogenesis.
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