Order in Nature

                It’s spring!  Not that this winter on the East Coast was bad, but I am always happy to leave those cold months behind.  I like being able to roll out of bed, put on some flip flops and walk to the bagel store at 8am on Saturday without being cold.  In fact, I like walking anywhere without being cold.  I’m not a big fan of cold.  Or wind.  Or the word “blustery.”  

                The upturn in temperatures means more greenery, more life outside and more flowers.  One of my most (er, only) favorite parts of living in Boston was the Public Garden in springtime.  The flowers and trees were always so gorgeous.  Now I have cherry blossoms to look at and petals flying all over Rittenhouse Square in Philadelphia.  I still love it.

                Here are some beautiful photographs of flowers that I found on NationalGeographic.  

                So pretty.  So ordered.  Life is very ordered, is not?  These flowers have very specific patterns.  The body of a human being is a well-engineered machine.  People build homes, cities, and roadways to create order out of the world.  Our computers have files that are logically organized and our homes have places for just about everything.

                But then… things aren’t ordered, are they?  I’ve neglected my apartment for the past two months due to illness (damn kidneys!) and it swiftly became a war zone.  Bring one baby into a home and blankets, toys, bottles, and diapers are quickly strewn about.  It takes a lot of energy to keep things organized and almost none to mess it up.  

                In science, we talk about entropy (also referred to as S) and often times equate it to the degree of disorder in a system.  Higher entropy means more disorder and lower entropy means less disorder.   Just as a ball will roll down a hill or heat will flow from a warm place to a cold place, systems tend towards states of more disorder.  By sheer probability, this has to be the case.  Think about a deck of cards.  There is only one way that deck of 52 cards is ordered (in a stack on the table), but there are literally millions of other ways the cards could be thrown around the room.  The probability of your deck of cards being a mess is nearly 100%.

                The second law of thermodynamics states that the entropy of the universe is always increasing.  This means that the universe is always moving towards more and more disorder.  If that is true, how do we explain those beautifully, ordered flowers?  Or living organisms with organized bodies?  Or any kind of order in our world?

                Let’s use the example of the deck of cards.  

   We are going to call the deck of cards our system and everything else the surroundings.

System:

Imagine that all 52 cards are randomly spread across the floor.  That deck of cards has a large amount of entropy. 

Now, you pick up the cards, organize them and stack them neatly on the table.  The deck of cards now has a small amount of entropy.

Scientists like to talk about the change in the system.  A natural question for a scientist to ask about our system now is “What was the change in entropy?” 

Change in entropy can also be written as ΔS and means this:

(Entropy of the final state of our cards) minus (the entropy of the initial state of our cards)

For our purposes, the actual number is not important.  We are more interested to know if that number is positive or negative.

What was the entropy of our final state of cards?  A small number.

What was the entropy of our initial state of cards? A large number.

A small number minus a large number equals a negative number.  

If you told a scientist that the ΔS of your system was negative, he would know immediately that your system went from more disorder to less disorder.

Surroundings:

Systems don’t live in vaccuums.  Depending on what the system does, the system will absolutely affect its surroundings.  If the system heats up, that heat will dissipate into the surroundings.  If the system cools down, it might draw heat from the surroundings into it.  These two parts are intertwined.

So, by picking up the deck and organizing the cards, what have we done to the surroundings?

A person came in, moved around haphazardly scattering air molecules all over the place.  The deck was placed together and probably tapped around a lot to make cards match in height, which probably increased the heat and movement of the air molecules.  Before that person came in, the air was calm.  

Think about what the ΔS of the surroundings would be.

What was the entropy of our initial state? Low.  Lots of order.

What was the entropy of our final state?  Higher.  More disorder.

A large number minus a smaller number equals a positive number.

If you told a scientist that the ΔS of your surroundings was positive, he would know immediately that your surroundings went from less disorder to more disorder.

Second Law of Thermodynamics

This law says that the entropy of the universe is always increasing.  It is always going from less disorder to more disorder.  ΔS universe is always positive.  

So, why did we spend so much time talking about a system and surroundings?

Because this is how the three are related:

ΔS universe = ΔS system + ΔS surroundings

The second law states that ΔS universe must be a positive number.

ΔS system + ΔS surroundings must equal a positive number. 

For our case:

ΔS universe = negative number + positive number

As long as the surroundings become very disordered (a large positive number), then the ΔS universe will be a positive number. 

If you look at any system and surrounding situation in nature, carefully measure its entropy changes and add them together, you’ll always get a positive number.  If they don’t add up to a positive number, then it does not occur in nature.

So, the flowers and people and organized life exist in this world.  If you think of them as systems, then their entropy is definitely decreasing.  However, they must disorder their surroundings quite greatly to compensate.  This is also true.  People are constantly moving, breathing and changing their surroundings.  Plants are no different.  Living organisms are constantly uptaking some nutrients and giving off others.  Their surroundings are always changing.  As the organism gets more ordered, the surroundings become more disordered and so the universe becomes more disordered and we’re all here.

Okay - if I've totally confused you, then here are more pretty flower pictures to relax your brain.

REFERENCES

Zumdahl, Steven S. “Chemical Principles, 4^th Edition” (2002) Houghton Mifflin Company, Boston, MA.

Fluorescent Proteins

This is how I wanted the title for this post to look:

Fluorescent Proteins

                On Mini-Amedeo, I posted a story about fluorescent sushi.  While a little unsettling if you’ve never seen something like this before, I assure you that the technique used to make these fish fluoresce has been known for quite a long time, heavily studied and remains a popular scientific tool.  Yes, the fish are “genetically modified,” but that’s a fancy (and somewhat unnecessarily nerve-inducing) term that really means scientists have added one extra gene into the fish (See Central Dogma post for information on genes and proteins).  Genetic modification is not a new idea.  It’s been done since the dawn of agriculture, but that is a topic for another day.

                So what is this gene that scientists inserted into the fish?  The gene for Green Fluorescent Protein, also referred to as GFP.  Ooooh.  What an interesting and rather self-explanatory name!  As it implies, under the right conditions the protein fluoresces green. 

                In the 1960s, GFP was discovered in Aequorea victoria, which is a jelly fish found off the west coast of North America (Figure 60.1).  The gene to encode the protein was isolated from the jellyfish in 1992 – 1994.  Scientists were able to use known techniques to place the GFP gene into other organisms, who then express the GFP and – viola! –  we have glowing fish.  Or cells.  Or mice.  Yes, I’ve seen them all.

                Would you like to see what GFP looks like?  I hope you said yes because it’s coming in Figure 60.2 regardless!       It’s a very pretty protein.  The 11 diagonal bands represent 11 beta strands (Protein Folding post) that create a barrel shape with a hollow center.  An alpha helix, which is responsible for the fluorescent qualities, sits in the center.

                Knowing the structure of the protein allowed scientists to tweak it.  Instead of fluorescing green, a new version of the protein could fluoresce blue (blue fluorescent protein, BFP).  Another could fluoresce yellow (yellow fluorescent protein, YFP).  Very soon, an entire rainbow of colors was available to the scientific community.

                What were scientists doing with these proteins?

                In the Central Dogma post, I discussed the organization of a cell.  Let’s say you knew that a particular protein is present in your cell but you don’t know where in the cell the protein is found.  For example, does the protein stay in the nucleus?  Does it hang out around the plasma membrane?  Is it just all over the cytosol with no real localization?

                One way to find out is to create a long gene that encodes GFP and your protein of interest together.  Wherever your protein of interest goes, your GFP will go as well.  The two proteins are said to be “fused together.”  You can put this long gene into your cell, let it express the fusion protein and then see where GFP fluoresces.  Wherever the GFP is, so is your protein.  The schematic idea of this is outlined in Figure 60.3.  

Figure 60.4 shows you some real images of cells that I made a few months ago.  You can clearly see red fluorescent protein (RFP), GFP, and cyan fluorescent protein (CFP).  Each color represents a different fusion protein and is telling me where things are located.

This may seem trivial (or really cool!), but in reality the discovery of GFP and the subsequent tweaks that were made to it to create an entire arsenal of colors was huge to the scientific community.  There are other ways to determine what proteins are doing in the cell, but this way is so clean and simple compared to the others.  In fact, the contribution was so great that in 2008, Osamu Shimomura, Martin Chalfie, and Roger Tsien shared the Nobel Prize in Chemistry for their work on these proteins.

I met Roger Tsien in 2005 during my first year of graduate school.  At the time, I thought he made pretty colors and his research was interesting; today I realize just how much his work allows me to do my own.

NOTE: I chose to not discuss how fluorescence works in this post.  However, you will notice that the pictures of glowing sushi are all under a black light.  That is necessary.  All the cell images I show you in Figure 60.4 were also taken by shining a similar light on the cells.  Under what conditions things fluoresce is specific and sometimes requires specific light shone on them before they will glow.  If I do a post on fluorescence in the future, I will definitely link back here! 

NOTE 2: Incidentally, if you cook the fish, then it will no longer fluoresce.  The ability to fluoresce is dependent upon a properly folded GFP protein.  Cooking destroys the folding of most proteins.

REFERENCES

History of GFP, Nobel Prize: Roda. “Discovery and development of the green fluorescent protein, GFP: the 2008 Nobel Prize.” Ann Bioana Chem (2010) 396, pgs 1619 – 1622.

GFP Crystal Structure: Ormo et al. “Crystal structure of the Aequorea Victoria green fluorescent protein.” Science (1996) 273 (5280), pgs 1392 – 1395.

PDB ID code for GFP: 1GFL (www.pdb.org), images were rendered in PyMOL

Progeria

EDIT: There's now an update to this post concerning a new drug treatment!  Check it out: Progeria: Possible Treatment.  There is also another post on Dr. Amedeo concerning this same topic: Progeria Hope!

                Last night, as I was nursing my severely battered urinary tract with lemon tea on the couch instead of red wine in a restaurant, I was sucked into “20/20: My Strange Affliction” on ABC.  While clearly a rip off of TLC’s “My Strange Addiction,” I still watched.  C’mon – one woman counted her 123 cats.  I was horrified.  Luckily, a far better program followed: Barbara Walter’s Special “Seven Going on 70.”  There, I was introduced to Lindsay Ratcliffe.  

                She was, quite frankly, amazing.  The first grader from Flat Rock, Michigan was diagnosed at 4 months old with Hutchinson-Gilford Progeria Syndrome (progeria).  Her parents, Joe and Kristy, encourage her to live life to the fullest.  Watching the wee girl play T-ball and run in an impossibly large batting helmet on her tiny bald head tugged at my heart strings.  When interviewed, she was smiling, talkative, and full of happiness.  Check out the links at the bottom of this post – you will just want to give her a giant hug.  Or, just look at her picture!

                The reason I was so taken with her is because she and her family face a tough road: average life expectancy of those diagnosed with progeria is 13.  The disease causes the body to age eight times faster than the rest of us.  This leaves small Lindsay with stiff joints, small stature, loss of body fat and hair, as well as aged internal organs making her susceptible to diseases of the elderly: heart disease or stroke.

                68 cases of progeria are known worldwide making this disease incredibly rare.  For every 4 – 8 million children born, one will develop progeria.

                While this disease is not hereditary, it is caused by a mutation in one gene: LMNA.  This gene encodes for the protein Lamin A, which is responsible for the structural integrity of a cell’s nucleus.  The mutated Lamin A protein is shorter, doesn’t function properly and has been given the name progerin.  (Lost?  Need a review of cells, genes, and proteins?  Check out my Central Dogma post!)

                A quick look at the “What’s New in Progeria Research” page on www.progeriaresearch.com, shows that the actual changes within cells harboring this mutation are more complex than “oh, my nuclei are unstable.”  For example, a 2011 paper published in the Journal of Clinical Investigation showed that progerin is produced in small amounts by all healthy cells (those in you, me, and those in patients with progeria) and their levels increase with age.  Researchers feel that studying progeria and progerin will not only teach us more about this rare disease but also about the normal aging process.

                Aging is a hot button topic these days in science research.  Caloric restriction, resveratrol (see The GreatSirtuin Debate on Dr. Amedeo) and now progerin are pushing the boundaries of what we understand about aging.  This will continue to be an evolving and interesting field in the years to come.



Here is some info about a fund raiser held by Lindsay's parents on May 12th called Miles for Miracles: LINK

               

REFERENCES

Barbara Walter’s Special: http://abcnews.go.com/2020/barbara-walters-progeria-special-young-girls-living-progeria/story?id=11586041#.T10oqfUSHFk

About Lindsay Ratcliffe: 

http://www.monroenews.com/apps/pbcs.dll/article?AID=/20060502/HEALTH/105020022

http://www.myfoxdetroit.com/dpp/health/learn-how-to-help-lindsay-ratcliffe-20110520-mr

www.littlelindsay.com

Progerin Research in Journal of Clinical Investigation: Cao et al. “Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblases.” (2011) JCI 121(7), pgs 2833 – 2844. 

Progeria Research: www.progeriaresearch.com

Stats.

From the National Kidney and Urologic Diseases Information Clearinghouse:

8.1 million visits to the doctor are due to urinary tract infections (UTIs) each year.

The lifetime risk for a woman having a UTI: 50%.

20% of young women with a first UTI will get another one.

Men are less likely to have UTIs but they are more serious if they do occur.


Why am I sharing?  In January, I wrote about my experience with pyelonephritis (kidney infection).  Lucky for me, I was able to put my new found skills to good use when I developed a second infection a month later.  Yes, folks - that is two kidney infections in two months.  Don't be jealous.

It's been too long since my last post, but I'm trying to put my life back in order.

Stay tuned.  I'm nearly back to a fully functioning adult again.


REFERENCES

More info on UTIs and kidneys: http://kidney.niddk.nih.gov/kudiseases/pubs/utiadult/