Thirty. One.

                Here we are.  Today, the 31^st day of August, is also my 31^st birthday and, coincidentally, the publishing of my 31^st blog post.  We have a theme.

                Let’s talk about the number 31.  

                It’s a prime number.  No other number will divide evenly into 31 other than 1.

                The element on the periodic table corresponding to the atomic number of 31 is gallium.  I hate to tell you that I know nothing about gallium except that is sits between zinc and germanium, and above indium but below aluminum on the periodic table.  To quench my ignorance, I did some reading.  This particular element was discovered by Paul Emile Lecoq de Boisbaudran.  It was joked for a long time that he named this element after himself.  Lecoq, meaning rooster in French (if you put a space between the e and c), is gallus in Latin.  However, he adamantly denies this and claims it was really after the Latin word Gallia, a historic region of Western Europe that included present day France.

                I looked for notable scientific achievements that occurred in 1531, 1631, 1731, 1831, and 1931.  I came up mostly empty.

                However, I learned that several Nobel Prize winners were 31: Tsung-Dao Lee (Physics, 1957), Carl D. Anderson (Physics, 1936), Paul A. M. Dirac (Physics, 1933) and the man that spawned the rest of this post: Werner Heisenberg (Physics, 1932).

                Born December 5, 1901, Heisenberg published his theory of quantum mechanics in 1925.  He won the Nobel Prize in 1932 “for the creation of quantum mechanics, the application of which has, inter alia, lead to the discovery of allotropic forms of hydrogen.”

                Do not fear – I’m not going to spend the rest of this post describing quantum mechanics in any detail.  That would be … difficult.  Instead, I’m going to just talk about one little part of it: waves and particles.

                Let’s first set the scene on how scientists were viewing the world prior to quantum mechanics.  The macroscopic world (trees, cars, people, baseballs, etc) all behaved in ways that well-defined classical physics equations could predict.  For example, if a cannonball was shot at a particular degree from the ground with a particular initial velocity, classical physics could do the math and say (rather accurately) where it would land.  They could use math and initial conditions to predict future events.

 However, the microscopic world (atoms, electrons) did not follow these equations.  Try as they might, scientists could not explain the microscopic world.  It was a head scratcher for awhile.   

Finally, the theory of quantum mechanics was proposed as a model of the microscopic world.  It allowed scientists to use math and initial conditions to predict future events.  It works reasonable well and, as a chemistry major in college with a particular penchant for physical chemistry, I spent a great deal of time learning the equations and theory behind this excessively complicated model.  I’ll spare you the details!

Before quantum mechanics could be developed, however, scientists had to learn to think about things differently.  And now!  So shall you.

Think about a baseball.  If you had to define it as a particle or a wave – what would you choose?

Now think about light.  If you had to define it as a particle or a wave – what would you choose?

Classically, a baseball would be particle and light would be a wave.  That should seem familiar, yes?  A baseball is an object that can be seen, held, and touched.  Light, on the other hand, flies through the air at the fastest speed possible, we cannot hold light in our hands and we talk about light in terms of wavelengths.

But … what if we flipped it?  

What if we asked: Does a baseball ever act like a wave?  Does light ever behave like a particle?

The answer is yes on both fronts.  I can even give you examples.

Waves Behave like Particles

                The best example of this is the photoelectric effect, which was explained by Albert Einstein in 1905 when he published his theory detailing quanta of light.  These quanta are now known as photons.  

            

                In the experiment, light was shone on a piece of metal.  When the metal was exposed to lower energy RED light, nothing happened.  In contrast, when the metal was exposed to higher energy VIOLET light, electrons started moving across the surface.  Why?

                A metal surface is really rows and rows of metal atoms.  Atoms are composed of protons and neutrons in their nuclei and electrons spinning around the outside.  Shining VIOLET light on the metal was actually allowing electrons to be pulled away from their metal atom and move independently.  The RED light could not do this.  In order for an electron to be pulled from its nuclei, it had to be given some energy (the same is true if you want to hit a baseball really far – you have to put a lot of energy into a really awesome swing).

                Energy is associated with light.  That was understood.  It was also know that shorter wavelength of light (such as VIOLET light) has more energy than longer wavelength (like RED light).  Okay – it becomes obvious at this point that the energy associated with each color of light is playing a part here.  But, do the waves carry the energy?  That doesn’t make sense.

                And so this is where the understanding of the experiment ended until Einstein came along.  He said, rather succinctly, that the energy associated with each light is carried in small packets called photons.  The photons from VIOLET light hit the metal, transfers their energy to some metal electrons, and those electrons now have enough energy to get away from their nuclei.  The photons associated with RED light just don’t have enough energy for the electron to get way so nothing happens. It is an eloquent theory and a beautiful explanation.

                By definition, photons are particles.  Light has been traditionally treated as a wave.  This experiment could not be explained with waves but could be explained if we treated light as full of particles instead.  

Huh.

Particles Behave like Waves

                I think most people are familiar with the idea that waves can interact with each other to create new waves.  If two waves are moving identically, their peaks can add together and their troughs can add together and you get a newer, bigger wave.  This is called constructive interference.  If the two waves are completely out of sync, the peaks will add with the troughs and a flat line will result.  This is called destructive interference. 

                If you shine light on a piece of paper with two slits, you will get a pretty light pattern (called an interference pattern) displayed on your wall.  This is due to the light waves constructively and destructively interfering with each from each slit.  This experiment was explained quite well by the English physicist Thomas Young in the 19^th century.  

                Let’s say – just for fun – that you shine one electron at a time on the piece of paper with two slits.  What do you think would happen?  An electron is a particle.  It’s quite a bit smaller than the slit so, in theory, it should just pass through.

                Oddly, weirdly, totally against common sense-ly, you will see is a diffraction pattern.  That particle, an electron, is behaving like a wave.  I kid you not.  

                What have we learned?  Waves can behave like particles and particles can behave like waves.  This idea was fundamental to setting up quantum mechanics (along with a lot of other stuff that I won’t get into).  How to explain an atom, where electrons were located and what energy would do to these microscopic systems became infinitely easier to explain if we stopped thinking about electrons as strictly as particles and started thinking about them as having wave-like properties as well.  This is called wave/particle duality.

                Sooo… do you have a wavelength associated with you?  Why, yes indeed!

                You can figure it out using the below equation, which was developed by Louis-Victor-Pierre Raymond, the 7^th Duke of de Broglie.  It’s called, quite simply, the de Broglie equation.

               

                 

                Happy last day of August!

Clarification: Yes, I realize my blog archive says 35 posts.  I was counting science posts only (not announcements that I'll be away or my initial "what in the world is this blog?" post).  Unfortunately, I forgot to add in one post so this appears to be my 32nd science post.  Close enough.  :-)

Photons: packets of energy that is associated with light.

REFERENCES

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

Oxtoby, David W. “Principles of Modern Chemistry, 6^th Edition”

Weeks, Mary Elvira. Journal of Chemical Education (1932). 9 (9) pgs 1605 - 1619.

http://www.nobelprize.org/faq/nobel_laureates.html

Hurricanes!

** Look out!  Hurricane Sandy is now taking aim for us! 10/26/12 **
** UPDATED 10/30/12 **

** This post has now been updated with final Irene information **

                Irene is raging outside my apartment at this very moment.

                I’ve been tracking her progress for the past week.  The National Hurricane Center website (www.nhc.noaa.gov) is fabulous for all things hurricane: satellite images, forecasts, storm preparedness, information on the Saffir-Simpson Scale and so much more.  Check it out!

                This week, I’ve decided to dedicate my post to past (and present) hurricanes, or tropical cyclones as they are also called.  Living on the northeastern coast means I don’t see too many of these storms up close and personal.  However, when they come, they are interesting, exciting, nerve-wracking, and destructive. 

My first experience (at age 5) came in the form of Hurricane Gloria: windy, rainy and overwhelmingly loud.  A shed flipped over in the yard next to our house and the aftermath on the street was mostly shredded branches and leaves. 

Hurricane Gloria

Dates: September 16^th, 1985 to October 2^nd, 1985 

At highest strength: Category 4 (maximum sustained winds of 131 – 155 mph) 

Hit: Bahamas, North Carolina, Long Island, Connecticut 

Name Status: Retired 

Fun Facts: First storm to hit Northeast of Us since Hurricane Agnes (1972) and first storm to damage NY/Long Island since Hurricane Donna (1960).

Hurricane Gloria was a Cape Verde type storm.  These types of hurricanes form off the coast of Africa by the Cape Verde Islands.  They have plenty of time to gain strength as they move over the warm Atlantic waters.  In a typical year, only two Cape Verde storms form but they are often the most intense.  The five largest Atlantic hurricanes on record were Cape Verde storms.

Another believed-to-be Cape Verde storm was The Galveston Hurricane of 1900.  Erik Larson (of “Devil in the White City” fame) wrote a book called “Issac’s Storm,” which explains this hurricane in great detail.  

What I found most ominous about this story was Isaac’s barometer.  The centers of tropical cyclones have very low pressure (which is why areas that have the potential to turn into hurricanes are called “tropical depressions”).  Typical barometric pressures are above 1000 mb (millibars, a measure of pressure).  Currently, Irene’s pressure is 950 mb, which is low.  Hurricane Katrina at its most powerful was 902 mb.  The Galveston Hurricane bottomed out at 936 mb and hit Texas a Category 4 storm.  In the days before rapid communication and sophisticated weather predictions, Isaac Cline’s barometer and his eyes were all he had.  At one point, the pressure dipped so low that Isaac believed the instrument to be broken.  Once he realized what was coming, however, it took a tremendous amount of effort to warn those in Galveston of the true danger.  This hurricane resulted in almost complete destruction of the city.  It was one of the most deadly and intense hurricanes on record.

A hurricane has a cyclone shape and, when quite powerful, a well-formed eye.  Some hurricanes are simply breathtaking from a scientific/natural formation viewpoint.  How can you not be awed by their beauty?  I added pictures of some famous hurricanes to the slideshow above and tell you a little about each one below.  Of course, once on land, these storms ruin people’s homes, businesses and lives.  They are to be awed and respected.

The facts below list their category at highest strength.  This is typically not the strength of the hurricane when it makes landfall, which is defined as when/where the eye crosses over land.  Hurricanes gain their power from warm ocean waters so when half the storm is over land, it significantly weakens.  These cyclones also weaken as they move northward due to cooler ocean temperatures.  For example, when Hurricane Gloria made landfall in Long Island, NY, it was a Category 1 storm.  When Hurricane Katrina made landfall in Louisiana, it was a Category 3.

Hurricanes are also not limited to the Atlantic Ocean.  The Pacific Ocean also has these storms, but they are referred to as cyclones and typhoons depending on where you are. 

Hurricane Andrew

Dates: August 16^th, 1992 to August 28^th, 1992

At highest strength: Category 5 (maximum sustained winds greater than 155 mph)

Hit: Bahamas, Florida, Louisiana

Name Status: Retired

Fun Facts: First named storm and only major hurricane of the 1992 hurricane season. 

Hurricane Floyd

Dates: September 7^th, 1999 to September 19^th, 1999

At highest strength: Category 4

Hit: Bahamas then ran north parallel to US East Coast

Name Status: Retired

Fun Facts: Third largest hurricane evacuation in US history.  The other two were due to Gustav in 2008 and Rita (below).

Hurricane Ivan

Dates: September 2^nd, 2004 to September 24^th, 2004

At highest strength: Category 5

Hit: Grenada, Jamaica, Grand Cayman, Cuba, Alabama

Name Status: Retired

Fun Facts: Cape Verde storm, 10^th most intense storm ever recorded; 4^th major hurricane of 2004; at its height, the storm was the size of Texas!

Hurricane Katrina

Dates: August 23^rd, 2005 to August 30^th, 2005

At highest strength: Category 5

Hit: Florida and Louisiana

Name Status: Retired

Fun Facts: Costliest natural disaster in US history; 6^th strongest hurricane overall

Hurricane Rita
  
Dates: September 18^th, 2005 to September 26^th, 2005 (note: this is three weeks after Katrina)

At highest strength: Category 5

Hit: Texas and Louisiana

Name Status: Retired

Fun Facts: More intense than Katrina; 5^th major hurricane of 2005

  

                Due to Hurricane Rita, 2005 became the only year with more than two Category 5 hurricanes. 

Hurricane Irene

Dates: August 20^th, 2011 to August 29th, 2011

At highest strength: Category 3 (maximum sustained winds of 111 to 130 mph)

Hit: Puerto Rico, Turks and Caicos, Bahamas, North Carolina, New Jersey, New York

Name Status: unknown

Fun Facts: First hurricane to make landfall in New Jersey since 1903!

Currently, Irene is a Category 1 and headed straight for Philadelphia and NYC.  Stay safe!

     

Here's the updated Irene picture and path:

      And pictures of flooding from Center City Philadelphia...

         All is well here in Philly.  The river receded, runners are back on the path, public transit is up and working.  We're back to business as usual!  I hear, however, the Vermont is enduring some of the worst flooding in ages and many many people are still without power up and down the east coast.  My thoughts are with you!  I hope things return to normal for you all very soon, as well!

REFERENCES:

Larson, Erik.  “Isaac’s Storm.” 1999. Vintage Books, Random House Publishing.  New York, New York.

Hurricanes: www.nhc.noaa.gov

 

Individual Hurricane facts/path pictures: www.wikipedia.com

Andrew picture: http://interestingmarketingtidbits.com/tag/hurricane-preparedness/

Floyd picture: http://earthobservatory.nasa.gov/Features/FloydIntro/

Katrina picture: http://www.hurricanekatrina.com/

Ivan picture: http://www.hurricanekatrina.com/

Rita picture: http://en.wikipedia.org/wiki/File:Hurricane_Rita_Peak.jpg

Swimming with Deadly Amoebas

UPDATE: I posted this article on Mini Amedeo but thought it should be added here, as well.  The article discusses a possible link between N. fowleri infection with the use of Neti Pots.  The article reminds you to only use boiled, distilled or sterilized water with them!  LINKY

This week’s news highlighted the deaths of three young Americans who were infected with the dangerous Naegleria fowleri amoeba.  Apparently, this amoeba rears its ugly head each summer and results in a few deaths among children who enjoy swimming in natural freshwater areas.  Infection is incredibly rare, however.  According to an article by Madison Park on CNN.com, only 2 – 3 cases are seen each year in the United States and the median age of patients is 12.  This means that in the past ten years, there have only been 32 reported cases.  Ms. Park dramatically compares this with the number of reported drowning deaths each year: 36,000.

                The Central for Disease Control (CDC) offers a few tips for preventing infection by the amoeba:

           Don't swim in high temperature, low water level and poorly treated areas

           Use nose clips or hold your nose while swimming

                      Don’t disturb the sediments of shallow water areas

      On the incredibly rare chance that someone becomes infected by this amoeba, symptoms resemble meningitis: high fever, vomiting, headache, neck stiffness.  In fact, when admitted to the hospital, the patient is normally treated as such until a spinal tap reveals the presence of N. fowleri.  

      What then?  Well… 95% of the time, the patient dies approximately 3 – 7 days following infection.  In 1978, one person survived and he is the only one recorded.  

                “The incidence of this disease is very very small, but when it happens it’s tragic.”

-          Francine Cabral, Microbiology professor, Virginia Commonwealth University School of Medicine

So what happens?  In short, while swimming, the amoeba becomes stuck inside the swimmer’s nose.  Unlike a parasite, N. fowleri is not hunting for a human to live inside; its final resting place is purely accidental.  However, once there, the amoeba needs food so it travels to the brain where it begins to eat neurons (brain cells).  A perfect storm of reactions happen then: brain damage due to traumatic neuronal death, reproduction of amoebas, immune system response.  These all cause the brain to swell and eventually choke it and the patient of life.

On this tragic note, one has to ask what types of interventions are available.  Currently, doctors inject amphotericin B (antifungal) into the brain and veins.  Given the extremely high lethality rate, it is not surprising that a few scientists are searching for something better.  

A recent paper from the journal Parasite Immunology discusses how N. fowleri actually brings about the death of individual brain cells.  Doctors say “The brain cells died.”  Scientists want to know how.  

Think about when a building is knocked down.  It’s easy to say “Yup, they tore that building,” but how the building came to be torn down is another matter.  Did they set up strategic explosives?  Did they use a wrecking ball?  

The how is extremely important because if we understand it, we might be able to stop it.  If we know that in order to successfully tear down the building, explosives must be set in exactly five places to weaken the structure, then we can exploit that information if we want to stop the building’s destruction.  The same is true of cells.  If know exactly how the amoeba brings about cell death, we can potentially block the amoeba’s action, which will starve it of nutrients and eventually lead to its death instead of the patient’s.

Okay… let’s discuss a little bit about cell death.

Cells kill themselves all the time.  It’s common, necessary, and very much a part of life.  The most well understood mechanism of cell death is called apoptosis.  The term comes from the Greek words apo (from) and ptosis (falling).  

Signals outside the cell can tell it that it’s time to die.  For example, during development, surrounding cells will tell other cells to die.  We aren’t born with webs between our fingers but they do exist for a time inside the womb.  Signals within the cell can also say it’s time to move on.  The sun damages our skin cells’ DNA or nutrients become too low, the cell will assess the situation and, at some point, finally conclude it’s time to pack it in and kill itself.

Cells are tightly regulated (post HPV: The Cell (cont’d Henrietta)) and if anything goes wrong, it knows to kill itself to protect the surrounding cells from its problems.  Cells are very thoughtful that way.

Anyway, apoptosis is a very logical process.  Following initiation signals (whether those stem from inside the cell or outside the cell), certain proteins are told its time to kill the cell.  These proteins talk to other proteins, which then perform all sorts of functions.  Scientists have worked out the communication signals and know which signals lead to which proteins and who those proteins talk to.  

We know how apoptosis works.  Because we know, we can exploit the predetermined steps that follow once apoptosis has started to potentially stop cell death.  In fact, this is one mechanism that HPV uses to keep diseased cells around.  Normally, infected cells would die upon infection by HPV, but the virus comes with proteins that disrupt the known signals involved in apoptosis and those cells stick around instead of dying.  Tricky virus, huh?  (If you want to read more about HPV, I direct you to the Series: Henrietta Lacks posts)

So, is N. fowleri inducing apoptosis in cells?  Is that how it is causing neuronal cell death?

The answer is no, but we are surprisingly close.

Many other kinds of cell death also exist that are equally organized and somewhat understood.  The authors considered authophagic cell death and necroptosis, as well.  

                They incubated T lymphocytes (a type of white blood cell) with N. fowleri and studied the morphology of the cells before and after.  The cells showed signs of necroptosis: swelling of intracellular organelles, plasma membrane lysis, and condensation of DNA (Figure 29.1).  They also studied various proteins in the cell and found that key proteins involved in apoptosis were not activated.  

In some final experiments, they pre-treated cells with a known necroptosis inhibitor and found that cell death was greatly diminished as compared to untreated cells.

More work needs to be done and large avenue of research will still follow this work, but understanding the how is half the battle to discovering ways to treat infection.  Perhaps one day, we’ll no longer have to read stories about these three dead children.  I want to say to their families that my sympathies are with them – no child should die in such a tragic and innocent way.

Neurons: an electrically excitable cell and that can process and transmit information (from Wikipedia.com)

Apoptosis: programmed cell death

REFERENCES

Park, Madison. “Brain-eating amoebas blamed in three deaths.” www.CNN.com (2011).

Link:  http://www.cnn.com/2011/HEALTH/08/17/amoeba.kids.deaths/index.html?iref=allsearch

Quigley, Rachel. “Brain-eating amoeba claims third victim as man dies after using tap water to clear his sinuses.” www.dailymail.co.uk (2011).

Link:  http://www.dailymail.co.uk/news/article-2027012/Brain-eating-amoeba-claims-victim.html

Song, K. J. et al. “Reactive oxygen species-dependent necroptosis in Jurkat T cells induced by pathogenic free-living Naegleria fowleri.” Parasite Immunology  (2011) 33, pgs 390 – 400.

Influenza Again!

EDIT: I updated this post to make it a bit clearer to a broader audience (8/15/11)

                When I finished up my Spanish Influenza series back in March, I did not expect to come back to it.  However, earlier this week I stumbled upon a blurb in Nature magazine that discussed a new area of influenza vaccine research.  I downloaded the paper, realized that it dealt with the hemaglutinin protein, which I’ve shown you pictures of, as well as the yearly flu vaccine that most people receive, and decided that this paper would be an interesting topic for all!

                Let’s start with antibodies.

                In response to viral or bacterial exposure (either through infection or inoculation), our immune systems produce antibodies.  In short, antibodies are proteins that can bind the invading virus both very specifically and very tightly and this binding leads to blocking of infection.  There are two key things to antibodies: specific/tight binding to virus and blocking the viral infection.

  Think of antibodies as policemen.  Once the city (body) knows a fugitive (virus) is within their boundaries, they gather lots of information on what he looks like (makes antibodies) and send the police (antibodies) after him.  Once they find him, the police are all over him (antibodies bind the virus), which blocks the fugitive’s ability to perform anymore harm.  

Figure 28.1 shows you the basic structure of an antibody.  All antibodies have the same overall structure, except for one area: the tips of the Y.  These areas change depending on what virus the antibody was designed specifically to bind.  For example, an antibody against the chicken pox virus (varicella) can’t bind the influenza virus.

In order for our bodies to produce antibodies, our bodies must first encounter these invaders.  We aren’t born with the antibodies against chicken pox.  However, once we are infected, we churn out antibodies to overcome the infection.  After infection, our bodies “remember” chicken pox in the form of these antibodies.  Should we ever encounter it again, we have the antibodies waiting to vanquish an infection before it has the chance to make us sick.

This is the theory behind vaccinations: inoculate with a weakened (attenuated) form of the virus or something that looks a whole lot like the virus and allow our bodies to form the antibodies.  Should we ever encounter the real deal in our lifetimes, our body has the antibodies waiting!

We are vaccinated against many things when we are children and most of them only occasionally need boosters.  Sooo – why do we need a new flu vaccine each year?

Ah.  Influenza is a tricky little virus!  

Figure 28.2 shows you the size of the virus relative to the size of an antibody.  The virus is pretty big in comparison, huh?  Clearly that little bitty antibody isn’t binding the entire virus.  

Think about the size difference between a human hand and a car.  Pretend the hand is the antibody and the car is the virus.  What can the hand, standing outside the car, grab on to?    Examples: the side mirror, a tire, the hubcap.  The hand can touch anything that is outside the car.  The hand would be unable to touch the seats or the steering wheel inside.

So, what do influenza antibodies grab on to?  Primarily, they bind the hemaglutinin protein that is a major coat protein to the virus (see Spanish Influenza series for more info).  Antibodies won't be able to grab anything inside the virus so they must aim for something on the outside.  Hemaglutinin is typically what they target.

Antibodies, which are similar in size to the hemaglutinin protein, are only binding to one specific part of the entire hemaglutinin protein.  This is called the epitope.  Nature doesn’t dictate exactly where the epitope needs to be so our bodies can make antibodies that bind to any part of the protein.  However, remember that antibodies have two goals: 1. bind the virus and 2. block infection.  While many antibodies will be able to bind the hemaglutinin protein, not all of those will be able to effectively block infection.  Not all antibodies are made alike.

The structure and amino acid sequence of hemaglutinin proteins change slightly every year because the virus is evolving.  Each year, scientists create a vaccine against the most prominent strains of the virus, and each year the influenza changes a bit to get around our antibodies.  It’s a constant cat-and-mouse game.

   Instead of guessing each year what kind of influenza will be around and relying on our bodies to make the correct antibodies, what if we had a different approach?  What if we designed a super antibody that could recognize hemaglutinin despite its yearly change and effectively block infection of all viruses?  What if, instead of vaccines, we just gave people this super antibody?  Would this work??  How would we go about finding such an antibody?

                     A study published last week in Science talked about how scientists are looking for an antibody that will do just that.  Called broadly neutralizing antibodies, these antibodies would be able to bind to all hemaglutinins and effectively block infection of the virus.  Such antibodies are rare finds, difficult to design de novo (from scratch) and previous attempts have lead to antibodies that aren’t very powerful at stopping infection.  However, Corti et al. discuss one particular antibody they were able to find that:

-          Tightly and specifically bound all hemaglutinin proteins currently known

-          Neutralized infection of known influenza viruses

This is actually pretty cool!

This one antibody was made by a donor's immune system and the scientists were able to purify it away from everything else in his cells to study how it worked.  This antibody is a needle in a haystack!

                Interested where this antibody was binding hemaglutinin (where its epitope is), the authors investigated and found it bound in the stalk region of the protein (Figure 28.3).  This area of the protein tends to be very similar among all hemaglutinins and doesn’t change much in the yearly influenza evolution.  

                What is even more fascinating is that they found the antibody to be protective when administered before influenza infection (prophylactic) or after, even with lethal forms of the influenza virus.

                The authors show quite clearly that the antibody is binding hemaglutinin protein specifically/tightly and they are able to show convincing results that this antibody can block viral infection when inside an animal.  From the viewpoint of the general population, this is good news and mostly what is interesting.  From the viewpoint of me, a biochemist, I want to know how.  How does an antibody binding a protein lead to blocking an entire viral infection?

                While they authors are not sure, they speculate at the end of their paper.  All three possibilities rest in the idea that the antibody is binding an area of the protein that is needed for successful viral infection.  For example, the antibody is holding an area of the protein in particular position and will not allow the protein to change from that position.  Or, perhaps the antibody is covering an area of the protein that needs to be cut.  If the scissors (protease) can’t get near the spot it needs to cut because a big old antibody is in the way, then it won’t happen.  Finally, maybe that area of the protein needs to bind something else but the big antibody is already there.  Based on what scientists know about hemaglutinin’s role in viral infection, all of these possibilities are valid.  However, which one is actually responsible remains a mystery! 

Inoculation: placement of something that will elicit a response, such as growth or reproduction.  In the case of vaccination, it places something in the body that will lead to an immune response and production of antibodies.

Varicella: scientific name for the chicken pox virus

Epitope: area of a protein that an antibody binds to

Prophylaxis: medical procedure performed with the intent to prevent disease

Protease: a protein whose specific job is cut other proteins apart

REFERENCES

Science paper in its full scientific glory: Corti et al. “A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza A Hemaglutinins.” Science (2011) 333, pgs 850 – 856.

An easier version for non-scientists to read: Wang and Palese. “Catching a Moving Target.” Science (2011) 333, pgs 834 – 835.

Lodish, et al. “Molecular Cell Biology.” (2004) WHFreeman Publishing, 5^th Edition.

Slideshow Pictures - Microscopes and Photography

               Several weeks ago, I put up a slideshow.  I didn’t tell you what the pictures were because it’s fun to imagine what they could be or should be before being clued in.  Today, I’ll reveal what each picture is and how the image was captured, but before we get into that, I’d like discuss a bit about “the small world.”  

                The human eye is capable of seeing large things.  We can easily discern trees, houses, cars and people.  On the smaller edge of life, we are able to resolve two blades of grass or two strands of hair.  Unfortunately, there is a limit to our eyes.  The “small world” is invisible to us if we only have eyes available to us as tools.  For example, we cannot see the cells and proteins that are running our bodies.  The limit of the human eye is ~ 100 µm (micrometers).    

                Luckily, to see smaller things, we have other tools available: light microscopes, electron microscopes, and crystallography (among other tools, such as atomic force microscopy).  Table 28.1 breaks down the size of what each tool will allow us to see and provides examples of some real world objects that are indeed that size.    

  

                                                                                                                                       

Tool	Smallest Size it can See	Examples
Human Eye	Down to 100 µm	Blades of grass, strands of hair
Light Microscope	Down to 0.1 – 1 µm	Cells
Electron Microscope	Down to 0.0005 µm	Large protein structures, viruses
Crystallography	Down to 1 Å (angstrom)	"single" proteins, atoms

Table 28.1 – Visualizing our “small world”

Light microscopy has come a long way from its humble beginnings.  Currently, scientists are able to manipulate cells and open up color and contrast to this “small world” that our eyes can’t see.  We are able to insert fluorescent proteins into cells and watch them move around; we are able to stain certain places in cells to clearly see the outline of plasma membranes, nuclei, endoplasmic reticulum or Golgi bodies.  Thanks to Roger Tsien, Ph.D. of UCSD (University of California, San Diego), we are able to color these objects and all kinds of proteins with a whole rainbow of options.  And, most importantly, we able to see things happen in side cells in both real time and at points along the way.  Light microscopy is a powerful and valuable technique.

                Nikon (of camera fame) offers a contest every year called the Nikon Small World – Photomicrography Competition.  It is open to anyone over the age of 18 with an interest in photography of images taken through a light microscope.  (read = you do not have to be a scientist to enter and it is an international contest).  No limit exists on what the picture should be of, so you can see anything from cells to flowers to snowflakes in a highly magnified and colorful format.  First place is $3,000 towards the purchase of Nikon equipment (they are tooting their own horn here) and the pictures go on a tour around the country.  For the past several years, the exhibit had come to my place of work and I was able to see all the pictures.  Some of them are truly gorgeous!

                A few weeks ago, I went through the galleries of past exhibits (http://www.nikonsmallworld.com/gallery) and picked a few images that were visually interesting and/or showed a common object in a new way.  And thus, my slideshow was born.

2007 Winner of Nikon Small World Contest

Photographer: Gloria Kwon, Memorial Sloan-Kettering Institute (New York, New York, USA)

What is it? A mouse embryo at 18.5 days.  Mouse embryo is in red and the yolk sac is in green.  

Magnification = 17 times

2005, Image of Distinction

Photographer: Viktor Sykora, Institute of Pathophysiology, Charles University (Prague, Czech Republic)

What is it? Drosera scorpiodes – a pygmy sundew (carnivorous plant!)  Native to Southwest Australia

Magnification = 30 times

 2005, 12^th Place

Photographer: Edy Kieser (Ennenda, Switzerland)

What is it? Crystallized potassium chlorate.  Think of it as looking at grains of salt very closely!

Magnification = 40 times

  2010, 12^th Place

Photographer: Dr. Gregory Rouse, Scripps Institution of Oceanography (La Jolla, California, USA)

What is it? A juvenile bivalve mollusk (like clams, oysters, mussels or scallops).  This particular one is from the species Lima.

Magnification = 10 times

2010, Honorable Mention

Photographer: Dr. Alvaro Migotto, Centro de Biologia Marinha, Universidade de Sao Paulo (Sao Paulo, Brazil)

What is it? Enchinaster brasiliensis (a starfish!) embryo at four cell stage

Magnification = 60 times

1987, 1^st Place

Photographers: Julie Macklin and Dr. Graeme Laver, Australian National University, John Curtin School of Medical Research (Canberra, Australia)

What is it? Crystals of influenza virus protein neuramindase (see Influenza Series!)

Magnification = 14 times

If you are interested to see if the Small World Exhibit comes near you, check out this website: http://www.nikonsmallworld.com/tour

Want to see how a light microscope works?  Here’s a wonderful website from one of my favorite podcasts/websites: http://science.howstuffworks.com/light-microscope.htm

I guess I need a new slideshow now!  I’ll work on it.  Stay tuned!

Micrometer: 1 micrometer = 1 x 10^-6 meters or 0.000001 meters (super small!)

Light microscope: uses light and two lenses to magnify images

Electron microscope: uses electrons to illuminate objects instead of light

Crystallography: a technique that shoots X-rays at proteins to discern their structures

Atomic Force Microscopy: a technique that uses a very sensitive cantilever and tip to study surfaces.  It can sense height differences of < 0.001 µm.

Å(Angstrom): 1 Angstrom = 1 x 10^-10 meters or 0.0000000001 meters (über small)

REFERENCES

Roger Tsien’s Laboratory: http://www.tsienlab.ucsd.edu/

Nikon Small World official webpage: http://www.nikonsmallworld.com/