Biology Midterm Study Notes
Studies biological systems by perturbing them (biologically, genetically, chemically) and
monitoring the gene, protein and informational pathway responses; and ultimately, formulating
mathematical models that describe the structure of the system and its response to individual
perturbations… Integrated wholebody/organism approach.
Pros: good for chronic, complex diseases like diabetes
Cons: less control over variables, less mechanistic (what factor was the MOST important?),
1. Each adult human can be considered as a unique biological system
What Makes Us Uniqueier?
Nonreproductive sex is unique
Aggression we are not the only species that premeditates murder of its own species in an organized manner/genocide chimps
However we have unprecedented passive aggression (drone bombers sitting in an office killing across world)
Theory of Mind understanding others think different chimps dominant/submissive with banana
However we have secondary theory of mind recognizing this person knows something this other person doesn’t
The Golden Rule tit for tat optimization strategies cooperate when others do and compete when they do you wrong bats
(mothers feeding/not feeding each other’s babies) and beta fish do this too
Empathy chimps an innocent bystander gets pummelled socially groomed, vs. one asks for it and is pummelled nothing
However we can feel empathy for other species (abused animals) and we can feel pain from PAINTINGS of horses in war
Reward dopamine not about reward but the anticipation of reward skyrockets with 50% reward rate, same for 25% and 75%
However we hold on for way longer in anticipation (ie reward in afterlife)
Culture nongenetic passing on of styles and behaviours
However our sheer complexity and magnificence is different in culture
Our contradiction to take the impossibility of something and think that makes it more possible the less lovable a person
is, the more they must be loved… The less… the more______.
2. Our biological system has a Control and Communication Network
CCN Components which all interact: • Central Nervous System brain and spinal cord
• Peripheral Nervous System somatic and autonomic nervous system
• Endocrine System endocrine tissues and exocrine glands
• Local Support and Defense System maintenance and support, adaptation and repair, resident and migrant defense
3. The CCN is the logic unit and controls information
• It’s always on
• Information flow within the network is via chemicalbased, cellcell communication
• The components of the CCN are not separable supports that emotions and thoughts are biochemically based
4. CCN is the locus of health
• Integrator of seven dimensions of health: spiritual, emotional, social, mental, physical, occupational, environmental
5. Aging and disease represent compromised function/structure of CCN
• Many disease processes result from abnormal function of CCN, ie. diabetes & endocrine, ADHD & central nervous
• Reduced function of CCN with aging, ie. impaired memory & central nervous system, impaired wound healing & local
support and defense
6. A systems biology and communication networkbased approach to health, disease,
and aging is anticipated to facilitate enhanced medical and healthcare practice
• P4 Medicine personalized, predictive, preventative, participatory
• However, the patient is very responsible to be participatory
• And many people will be making money off of people’s fears online ads for genetic screening for cancer
Research in Medicine and Healthcare
Categories of experimental ‘model’ systems for human medical and health research: A. Simulations with mathematical models/computer, mechanical and chemical techniques
B. In vitro (petri dish) and exvivo (water bath) – cell culture, isolated tissues/organs
C. Animal models
D. Human subjects
Animal ModelsNematodes and Fruit flies
• Easy to study, cheap, selffertilizes, can be frozen and thawed
• Transparent can use fluorescent tags and follow digestion of a nutrient or synthesis of protein
• Fruit flies life cycle and development are sensitive to environment, used to study drugs and alcohol
Animal Models Lab Rats
• Social and intelligent
• Used to study lifestyle effects on metabolism (diets, exercise, drugs)
• A more severe approach than with humans, ie. 10 hrs of intense exercise per week
• Not a good model for human infants
Animal Models Lab Mice
• Applying recombinant DNA technology (knockout a gene, overexpress a gene, etc)
• Test the importance of a single protein
• Used to study lifestyle effects on metabolism but are different than rats mice take longer to become insulin resistant
• *Recall Leptin Slide
Animal Models Lab Swine
• Piglets are best nonprimate model for human infant development and metabolism
• Used to study organ transplants
Animal Models Lab Primates
• Closest to human model, BUT ETHICS?! COST?!
• Used to study human pathologies (like AIDS), transplants, drug abuse and toxicology
Basic Experimental Design of Human Medical and Healthcare Research NonIntervention Studies (nonclinical)
No treatment given
Can’t prove cause and effect; predicts associations/correlations
Epidemiological studies are common
Intervention Studies (clinical)
A medicinal treatment and a control substance/placebo is given
Can predict cause and effect
Doubleblind clinical trials are ideal
**But, do you see this in the real world? How well was the study designed?
Human Clinical Trials
Order of Tests for a New Drug:
Test on laboratory animals
Phase I Clinical Trial: Is it safe for humans?
Phase II Clinical Trial: Does it work for its intended purpose?
Phase III Clinical Trial: How does it compare with other available treatments?
Accountability of Media for Relaying Accurate Information
*** Recall headline examples
New Dimensions in Medical and Healthcare Practice
A. Evolutionary Medicine
We get very little exercise… inactivity used to be taken as a signal that we were injured and needed to initiate and
Improved sanitation has increased life expectancy… but a reduction in normal intestinal parasites may affect digestion,
allergies and healthy
What if our fight or flight response is always on? Elevated cortisol levels due to stress are treated like a physical threat
B. Integrative Medicine
C. Collective Medicine Our environment impacts our health ie. asthma and air pollution, mercury in fish
D. Enhancement Medicine
Botox, Viagra, fertility drugs, laser vision, nootropics (brian enhancers) boost acetyl choline, omega 3 for brain?
Dimension of Time
Trajectory (growth, development, aging ▯ months, years, decades)
Healthspan (healthy and independent) vs lifespan (how long do you have to live)
Rhythms (maintenance, repair, etc. ▯hours, days, weeks, months)
Homeostasis (maintenance of steady state ▯ seconds, minutes, hours)
Energy and Information Flow (action potentials and enzymatic reactions ▯ nanoseconds to
Biomarkers: indicators of the biological state of an organism
Measuring height in infancy and childhood is important in assessing health early in life
Slow growth infection disease, malnutrition, hormonal problems
Fast growth overnutrition, excess growth hormone
Height during the adult lifespan looks more stable… until you change the scale and have a closer look
A decrease in height later in life may be attributed to bone degeneration
Muscle mass decreases with age as well in males due to a decrease in testosterone and inactivity, in females due to
Reconsidering Blood Glucose from a Time Perspective…
Oral glucose tolerance test is easy to cheat on the week before
Sugar residues attach to hemoglobin and it’s nonreversible
Gives a longer view and it is very hard/impossible to cheat
However, inconsistent methodologies across different labs
Requirements of a biomarker: • Needs to reflect normal function, disease processes or predict the risk of future development of disease
• Must have a predictable range across an identifiable category of individuals, or can be monitored over time in one
• Must have methods available for accurate and precise measurement
Most biomarkers have normal ranges and diagnostic value if they are too low or too high.
Biomarkers can change throughout life: must be interpreted in relationship to age, sex, and physiological state of patient
Example: VO2Max declines with age due to a decrease in max heart rate, muscle mass and training intensity
A New Era in Biomarkers:
We can look at changes in clusters of genes, proteins, metabolites relative to a “norm”. Developing “Dynamic Network
Biomarkers” looking at changes in relationships between clusters, is based on the assumption that static biomarkers don’t really
track the transition from a normal to a diseased state and we can’t catch them until late predisease usually.
**See practice questions
The study of timescales and cycles in biology.
Ultraradian (less than 24 hours appetite ghrelin (meals), cortisol cycle)
Circadian (24 hourscortisol: nadir midnight sleep initiation, peak @8am) HPA axis dysfunction associated with abnormal sleep
cycles (shiftwork) this can cause health effects
Infraradian (more than 24 hours menstrual cycle)
Change in Height and Bone Density
Change in height has significant limitations as a biomarker of osteoporosis because it needs to be measured over time in each
individual and doesn’t change a LOT, and is very gradual. Height also naturally changes over the course of the day and it doesn’t
directly precede, or predict the disease state.
Biomarkers that are gradual or change suddenly are not very helpful in predicting health problems.
For osteoporosis, a bone density scan is a pretty good measure. Usually the head of the femur and lower spine are measured
because they are weight bearing.
Maximize bone density in a 2030 year old:
Consume sufficient calcium in adolescence and early adulthood
Adequate vitamin D
Weight bearing physical activity and maintain a stable body mass
***Bone density can be hindered by smoking, alcohol, caffeine, and phosphates because they either block the
absorption of calcium or make you pee it out It is so easy to lose bone density because bone serves as a functional calcium store in the body and acts as a “buffer” for plasma
calcium levels. Plasma calcium must be maintained over a very narrow range for normal cell signalling and generation of action
Are controlled by peripheral “clocks” governed by the “master clock” (hypothalamus), it controls gene expression of
enzymes/proteins that affect many metabolic processes.
Coordinate sleep, nutrient supply and activity patterns with the metabolic patterns required at different stages of the day.
Their disruption in experimental animals causes a wide spectrum of health problems and premature aging:
Impairs gastrointestinal function (ulcers, irritable bowel)
Obesity and metabolic syndrome
The master clock is in the “suprachiasmatic nucleus” which keeps time based on light signals from the retina. Nearly every cell
in the body also has a subsidiary clock which is slave to the central clock, coordinating its metabolism with the rest of the body.
Peripheral clocks also receive cues from things like food intake. We still don’t know a lot about the molecular clock (oscillator).
Shift workers tend to experience a greater incidence of:
Obesity, diabetes, cardiovascular complications
**Late chronotypes (OWLS) seem to suffer a conflict between internal and external time, called “social jetlag”. They are more
likely to suffer from mental stress and more likely to smoke. Physical exercise and melatonin can help resync sleepwake cycle.
Relevant health examples of circadian rhythm:
Glucose tolerance is greater in the morning in normal weight people better insulin sensitivity, but no such rhythm in
overweight people. Practicality: bigger meals in morning? A factor in diabetes testing?
Risk of sudden heart attack is greatest in midmorning. No real answer yet. Combination of factors: caffeine, stress,
sausage McMuffin, etc.
Appetite is stimulated by ghrelin which is produced in the stomach. Ghrelin release is entrained by mealtime patterns.
Its postmeal decline is blunted in obese people and ghrelin increases with weight loss (harder to keep weight off?) It’s
been suggested that more protein at breakfast can help keep ghrelin reduced throughout the day. We can eat whenever
we want in our society which conflicts with our master clock and can dysregulate our metabolism.
Also… rodents are nocturnal but we study them during the day. How does this affect the research? Are there benefits to a reverse
lightdark cycle? Mechanisms of Intercellular Communication
1. Direct Communication
a. Gap Junctions
b. Tunneling Nanotubes
2. Indirect Communication
a. Chemical Messengers
Pore size is very small, allows passage of sugars, amino acids, ions
Connexons are important for regulation of cell growth and differentiation if the cells don’t communicate well it could
lead to loss of control over cellgrowth (cancer)
Intercalated disks in cardiac muscle contain channels for Na+,