The dream: just one shot

We are engaged in an arms race with the flu virus, but we have a secret weapon hidden in our DNA.  We can make antibodies that neutralize a bunch of different flu variants.

Viruses are little packets of DNA cloaked in proteins.  We make antibodies that target the outer protein shell, flagging the virus as an invader to be destroyed.  In the arms race, viruses evade detection by making constant changes to that outer coating.  But not the whole coating, just a piece of it that is referred to as the “head.”  We might gain a foothold in this race because the flu keeps the same “stem” region across many of its flavors, including H1N1 and the much-talked about H5N1 (avian flu).  In response to the pandemic 2009 H1N1 infection, some people made broadly neutralizing antibodies directed against that stem region. We all have the gene to do it; the trick seems to be finding the right immunogen to show to the immune system.  The seasonal vaccines we get at the doctor’s office haven’t been able to elicit such a response, yet, though people who have been exposed to many flu vaccines are more likely to have broadly neutralizing antibodies.  So all those shots you got weren’t for nothing.

Research is bringing us closer to that dream of a universal flu vaccine.  It’s been making headlines in the big journals this month. A paper published in Nature this week shows what makes for a good universal antibody and how the immune system needs to display it.  A paper in Science Express earlier this month found that people can make broadly universal antibodies that target both influenzas A and B.  If all the pieces come together, it could be the end of annual flu vaccines for future generations.


The social networking game

Our lives are dominated by social interactions that seem to be getting ever thicker.  We make new friends in real world, follow people on Twitter, circle people on G+, and add “friends” to our Facebook pages, to name a few.  What governs how we behave in these and other social situations?  And why do we have so many “friends”?

Turns out, we’re nicer when we get to pick our friends.  As for why we’ve got so many, it’s probably because there’s relatively little risk to expanding our network online.  When the stakes are higher, people tend to limit their interactions to people who are nice to work with.

These findings come from social experiments using the classic strategy game, the Prisoner’s Dilemma.  The game is played over multiple rounds, and in each round players choose between cooperating and defecting.  There’s fallout from either decision, based on the player’s action and the actions of his associates.  The game can be mapped to social, business, political, evolutionary, and environmental situations.

In this particular version of the game, dubbed “The Social Networking Game” by the researchers, players accumulated points based on their network of associates.  Points were assigned as follows, tallied throughout the game and players paid out based on their score:

Cooperator-cooperator:  4 pts each

Cooperator-defector:  -1 point to the cooperator, 7 pts to the defector

Defector-defector:  1 pt each.

Defectors in a sea of collaborators stand to be victors, but if everyone behaves that way, no one gets rich.  Each game went on for 12 rounds.  Between rounds, people could forge new bonds or sever existing ones.  In general, people chose to expand their networks with other cooperators and tolerated the few defectors, but those few bad apples eventually spoiled the barrel.

So the researchers modified the reward system to really penalize the cooperators for keeping those defectors around:

Cooperator-cooperator:  4 pts each

Cooperator-defector:  -5 point to the cooperator, 7 pts to the defector

Defector-defector:  -1 pt each.

Now people formed tight cooperating networks for almost the entire game (when players know how many rounds are in the game, they switch to defecting at the end in a last-ditch points effort).  Furthermore, early defectors were swiftly booted from the circle and essentially ostracized.

So what does it all mean?

In casual social situations, when we get to choose our colleagues and prune our social networks, we tend to wind up in groups that are highly collaborative. Especially when there are serious consequences for acting selfishly.  Of course, we can’t always choose who we work with, and these findings apply to decision-making in a wide variety of interactions.  But in a day-to-day context, putting ourselves in situations that allow for updating our networks probably has some social benefit.  Online social networks are a paradigm of picking who your friends are and pruning your network.  It’s sort of this experiment on a grand scale.  Perhaps, then, part of social media’s attraction?

Image credit:

Reference:  Cooperation and assortivity with dynamic partner updating.  J Wang, S Suri, DJ Watts.  PNAS, epub Aug 17th, 2012- open access publication.

Let the musical (r)evolution begin

The noise was fit enough to reproduce, so its genes were passed on to its daughters.

Can we use the scientific method to understand how music evolves?  Evolution, with all the trappings of tenth grade biology: heritable traits, genetic recombination and mutation, and survival of the fittest?  To find out, scientists in London and Japan wrote DarwinTunes, a computer program that applied the tenets of evolution to 8-second loops of computer-generated noise.  Then they watched as popular choice turned noise into music.

The noises were assigned a “genetic code” that could be shuffled around and mutated, much like our DNA.  Thousands of people voted on how much they liked (or hated) the noises.  The best loops were allowed to “reproduce,” or pass on their traits to the next generation.  Then people voted again.  This cycle went on for more than 2500 generations.  Through this process of (quasi-)natural selection, the researchers found that music quickly came from noise, complete with western rhythm and chordality.   You can listen to the evolution for yourself, here.

But then it stopped evolving.

Computer simulations aren’t the only place that musical change has plateaued.  It’s happening in real life, too. Scientists in Spain analyzed almost half a million popular songs recorded from 1955-2010, looking for changes in pitch (harmony, chords, melody), timbre (instruments used), and loudness (not how loud you blast it in your headphones, rather intrinsic loudness).  They analyzed these three traits within songs and across time.

The results are in.  If you grumble every time you turn on the radio, prepare your soapbox.  Newer songs basically sound the same, with simpler chord progressions and less instrumental variety.  Not only is this uninspiring to listeners, it could prove problematic for song recognition programs.  As for what has changed:  everything keeps getting louder.

Maybe social media will save us.  Yes, popular songs have the same ring.  But we have an Internet full of digital music.  As people explore and share songs that fall outside of this homogenous norm, we will probably see musical evolution pick up again.  Which gets back to the role of the audience in shaping new music.  As the creators of DarwinTunes point out, the line between audience and artist is easily blurred in our digital day and age.  Digital music allows people to tweak and re-share the original piece.  Audience-induced mutations could introduce a selective advantage that evolution just might favor.  Or, put more simply, seek out music that’s different, and mix up the stuff that’s not.


Photo credit:  Mark Runyon/

Original Papers:

Evolution of Music by Public Choice.  MacCallum et al.  PNAS July 24, 2012 vol. 109 no. 30 12081-12086

Measuring the Evolution of Contemporary Popular Western Music.  Serra et al.  Scientific Reports 2, Article #521.  July 26, 2012.  DOI:10.1038/srep00521

Reconciling the new with the old

There is constant turnover in cells lining the gut.  In fact, this happens as often as once a day by dividing stem cells that live in the mouth, esophagus, and intestines.  The nature of stem cells in the esophagus has become a matter of debate, and it’s an important one to resolve if we’re going to understand diseases that affect cell turnover, like esophageal cancer, which has increased 3-8 fold in just the past 40 years.

Studies on cell turnover in the gut date back to the 1960s, when researchers injected radioactive thymidine into young mice.  Thymidine, often represented by the letter “T”, is one of the four DNA base pairs.  As cells divide, they incorporate radioactive thymidine into their DNA, which lets researchers track the cells over time.  Using this technique, all cells appear to divide and mature at the same rate in the esophagus.

The funny thing is that more recent discoveries don’t match up with the original reports from the 1960s.  Over the past five years, people have reported small reservoirs of slowly dividing stem cells in the esophagus.  The original “all cells are equal” conclusion is tough to draw from radioisotope labeling, so it’s not surprising that it’s been brought into question.

Science marches on, and now we have much better technology to track cell fate than radioisotopes:  we have transgenic mice.  A paper from the lab of Philip Jones at the Hutchinson-MRC Research Centre in Cambridge capitalized on this technology to sort out stem cells in the esophagus. Their work was published online by the journal Science on July 19, 2012.

The Jones group used two different mouse models to resolve the nature of esophageal stem cells.  The first mouse can turn on green fluorescent protein in the nucleus of all its cells.  Flip a biologic switch by injecting a chemical, and all the cells turn green.  That green signal gets diluted out as cells divide and are sloughed off.  In fact, it’s gone after just a month.  So it appears that there are no slowly dividing cells.  This agrees with the 1960s report.

Their second trick was to use a mouse that can turn on yellow fluorescent protein in cells of the gut.  It works like the first, inject two chemicals and cells turn yellow.  However, this mouse is different in two important ways: only some cells turn yellow, and their offspring stay yellow.  So researchers could track the fate of yellow cells in the esophagus.  Did they all mature and get sloughed off, or did some stick around as a reservoir of future esophagus-lining cells.

Turns out, there is a population of stem cells that sticks around in the esophagus. They divide to maintain their numbers while sending an equal number of daughter cells off to replenish the esophageal lining.  When nothing’s wrong, they divide about twice a week.  In the face of injury, the esophagus is like a boxer, light on its feet.  The stem cells ramp up their number of daughter cells to fix the damage, then settle down and go back to maintaining the status quo.

These nimble cells set the esophagus apart from the rest of the gut, which probably contributes to some of the recent controversy.  Elsewhere, you’ll find small pockets of slowly dividing stem cells. Esophageal cancer and gastric reflux both affect the rate of cell division in the esophagus.  It’s important to know who’s calling the shots on cell turnover when trying to treat these diseases, otherwise we might miss out on finding new treatments.

The original paper:

A Single Progenitor Population Switches Behavior to Maintain and Repair Esophageal Epithelium, Science DOI: 10.1126/science.1218835Published online July 19, 2012.

Balancing Act

Blood vessels in a mouse retina. Endothelial cells are blue, perivascular cells are red and green.

The key to blood vessel growth is balance: too much, or not enough, of any one signaling molecule can have disastrous consequences.  Embryos can fail to develop.  Vessels can burst, clog, and leak.  Vessels can also respond a little too vigorously to a tissue’s plea for more resources, growing in a messy disarray of dead-end tubes that blood can’t flow through.

While papers on blood vessels date back more than 150 years, we continue to have new insights into their biology.  We learned about the cells that make up the vessels: endothelial cells, which form the actual tube itself, and perivascular cells, which sit just next to the endothelial cells.  Capitalizing on this, we started growing “vessels” in dishes, which lets us study how blood vessels respond to signals in their environment.  We discovered small, secreted molecules in living things that encourage new blood vessel growth.  We developed ways to inhibit those signals.  And still, there is more to learn.

The field of blood vessel growth (angiogenesis) spans many disciplines.  Beyond understanding the basics as they relate to developmental biology, blood vessels reach into cancer, eye disease, stroke, heart disease, gastrointestinal disease, complications of pregnancy, and more.  The benefit of this is that discoveries in one field can inform the others.  Across these fields, there have been increasing reports of blood vessel regulation by microRNAs.

MicroRNAs are tiny strands of RNA that regulate protein expression by degrading messenger RNA (which contains the “message” from DNA) before the message gets translated to protein.  Thousands of microRNAs have been discovered, but not all have been ascribed a function, and many have functions beyond those initially reported. They are named with numbers, generally in the order of their discovery.

A paper published by Dauren Biyashev and colleagues in the journal Blood on March 15th 2012 describes a new role for microRNA 27b.  In the complex web of arrows that can be drawn to “explain” the dizzying number of factors that prompt blood vessel growth or stasis, microRNA 27b may sit near the top, regulating both vessel sprouting and artery/vein assignment, by acting on several distinct pathways.

Biyashev and colleagues found that microRNA 27b levels respond to pro- and anti-angiogenic signals in the environment, and that this one microRNA can prevent the translation of at least six different proteins that regulate blood vessel formation.  As such, it is a dial that can be tuned with broad-reaching downstream consequences.

As a master regulator, MicroRNA 27b helps keep many signals “just right” during blood vessel development.  Understanding the central role of this microRNA, and the growth factors that regulate it, may provide new rationale for existing anti-angiogenic drugs, or lead to the development of new drugs that target the microRNA itself.


miR-27b controls venous specification and tip cell fate, Blood, March 15 2012, Vol 119 (11).

Angiogenesis is controlled by miR-27b associated with tip cells, Blood, March 15 2012, Vol 119(11).

The (soil) cycle of life

Decomposition is a great housekeeper: it takes care of dead plants and animals by breaking them down into simple molecules.  A variety of fungi, insects, worms, and bacteria are involved in decomposition.  The end result is that nutrients are returned to the soil for use by the next generation of plants.

Decomposition is important for maintaining the ecosystem, because there is a finite amount of matter in the world.  Think of it like a bunch of Legos: you can build a whole town, but then all your bricks are used up.  To build something new, you have to take apart the cars and buildings that you’re done playing with.  Then you can build something else with the freed-up pieces.

If you live in a town or city, you might not think about decomposition very often.  But out in the woods, you can’t miss it.  You’re often tromping on a thin layer of dead leaves that are square in the middle of being decomposed.  It’s long been thought that the main factor affecting the return of nutrients to the soil was simply how many plants were around to be decomposed.

Turns out it might be more complex than we thought.  In a study published in Science on June 15th 2012, Dror Hawlena, a post-doc in the Schmitz lab at the Yale School of Forestry, and his colleagues show that the rate of plant decomposition is affected by the predators in an ecosystem.

And it’s not because predators are eating the plants.

Hawlena and his colleagues stressed grasshoppers by raising them with a natural predator: a spider, but one whose mouth was glued shut.  The grasshoppers were under the impression that they could be dead at any minute.  Grasshoppers lived their lives, with or without the spiders present, died, and decomposed by the hand of microbes in the soil.

When prey animals, like grasshoppers, feel their lives are in danger, they want a constant supply of ready energy in case they have to make a break for it.  So, they eat more carbohydrates and break proteins in their bodies down into sugar.  While these behavioral and metabolic changes give the grasshoppers energy, they also alter the chemical composition of their bodies.  Carbohydrates have lots of carbon and not a lot of nitrogen, and the proteins that they dismantled were loaded with nitrogen. The combined effect of these changes is that stressed grasshoppers have a higher carbon-to-nitrogen ratio than unstressed grasshoppers.  Dead grasshoppers become part of the microbial diet.  True to the old adage, “you are what you eat,” that carbon/nitrogen imbalance is passed on to the microbes.

When the researchers piled dead grass on top of the soil where the grasshoppers had been, they found a surprise: microbes that broke down stressed grasshoppers were 200% less efficient at breaking down the grass.  The reason this is so surprising is that there was only a 4% difference in the carbon-to-nitrogen ratio between stressed and unstressed grasshoppers.  That small difference in body chemistry exploded into a huge effect on the rate of plant decomposition.

So, microbes eating stressed grasshoppers get less nitrogen.  Nitrogen is what microbes use to grow and to make the enzymes that break down dead plants.  Less nitrogen in the microbial diet probably means fewer microbes and fewer digestive enzymes in the soil, hence slower decomposition.

This doesn’t mean that we should mount a campaign against grasshopper stress.  Nature has a way of finding the right balance when left to its own devices.  But humans have a way of mucking with nature, so we need to keep in mind that the endangerment or extinction of high-level predators could have a ripple effect on the entire ecosystem; one that reaches deeper than we originally thought.


More reading:

Fear of predation slows plant-litter decomposition. Science. 2012 Jun 15;336(6087):1434-8.

Busy brain

Babies are born with brains that have a lot of circuitry laid down, but it’s not all wired up correctly from the get-go.  Like a young boy scout, the newborn brain is prepared for a lot of possibilities…it just needs a little help organizing.

That organization comes about through trial and error, especially for the visual system of the brain.  That makes sense- there’s nothing to see in utero.  The brain waits until it’s actually receiving input (light), and then trims the chaff soon after birth.  David Hubel and Torsten Wiesel figured out that brains are modified after we’re born in the 1960s; an observation that won them the Nobel Prize a few decades later.

Hubel and Wiesel saw that the brains of monkeys or kittens raised with one eye stitched shut are different from brains of animals raised with both eyes open.  Normally, equal brain space is devoted to processing left-eye information and right-eye information.  When animals are raised with one eye closed, much more space is dedicated to the open eye.  And it’s permanent: when that stitched eye is opened, it is missing appropriate visual processing power in the brain.  The eye can detect light, but the brain misses the signal.  As a result, that “seeing” eye is blind.

We have long understood that there is a critical phase after birth during which the visual system is setting up shop in the brain.  Now a paper published May 24th, 2012 in Neuron by Dorothy Schafer and colleagues in Beth Stevens’s lab at Harvard, describes a possible mechanism for that Nobel-prize winning discovery of fifty years ago.  In it, Schafer and her colleagues describe their findings that microglia, the immune cells of the brain, trim away superfluous connections between neurons to organize the visual sensory system.

As the brain’s immune cells, microglia are obvious first responders to disease and inflammation.  However, their role in healthy brains has only recently been appreciated.  Schafer, et al found that unused connections in the visual processing center of the brain get tagged for removal, and are subsequently eaten up by the microglia.  This idea isn’t such a stretch, since it’s normal for immune cells to “eat up” infected cells and cellular debris.  Apparently, they can also gobble up healthy connections in the brain that aren’t being used. Proper brain function depends the removal of extraneous connections early in development.

Schafer and her colleagues could muck with the system by preventing the microglia from recognizing the “eat me” signal, which led to a messy co-mingling of neurons from the left and right eye in the brain.  Normally, the left- and right-eye neurons are neatly segregated once the microglia have finished tidying up unused connections.

This paper makes use of the visual system of the brain, since it’s easy to manipulate.  Microglia are probably trimming unused connections in other areas of healthy, developing brains.  It will be interesting to see what else microglia turn out to be capable of doing, or not doing, as the case may be: some groups propose that faulty microglia may be partially to blame in neurodevelopmental disorders such as autism.  Swapping out a brain’s faulty microglial population for a new one wouldn’t be easy, but it’s probably not impossible.  If you’re interested, you can read a great article summarizing recent microglial work here.

Every organ system of the body has one or two obvious players.  The brain has neurons.  Those big hitters are what research has mainly focused on to date.  A lot of the peripheral cells were taken for granted:  microglia were “just” immune cells. As technology advances, these bystander cells are turning out to be more interesting than people originally gave them credit for.  A lesson for life in general, perhaps.