The Great Pumpkin is out to get you...

So, I have a calendar from the Nature Conservatory in the lab, and on it, for the month of October, there is a little blurb about pumpkins being treated with pesticides that are toxic to the human nervous system.  The chemicals in question are: malathion and diazinon, and they are neurotoxins... at least to bugs, which is why they make such good pesticides.  When it comes to humans, their toxicity is debatable.  Malathion, at the low doses used in agriculture, is completely harmless to humans (though I don't suggest drinking or eating it at higher doses).  Diazonin, on the other hand, can be more toxic, though, again, you should be okay unless you are eating or drinking it directly.  That being said, you should always was any pumpkins you plan on carving or cooking with.  AND you should always wash your hands thoroughly anytime after you've been handling any pumpkins.  Also, I agree with the Nature Conservancy in their recommendation to find a local, organic grower to avoid the chemicals altogether (you can find one at http://www.localharvest.com/).  The reason being that, while these chemicals are not harmful to humans, they can certainly be harmful to other, smaller animals that might raid a farm, and not have the benefit of being able to wash with soap or cut through the tough skin of the pumpkin with a knife. Plus, we don't want to have these chemicals build up in the soil and groundwater to the point where they reach concentrations that are toxic.  You can even look at your local grocery store to see if they sell certified organic pumpkins, if they are USDA certified organic, that means no chemical pesticides were used, and you and the environment can breathe a sigh of relief. 
Of course, I can't stop there because there's a great opportunity here to talk a little neuroscience.  I said that malthion and diazonin are neurotoxins, but what are they, and how are they toxic?  Both are chemicals of a class known as organophosphates, and both are cholinesterase inhibitors, which means that they block the action of an enzyme in the nervous system called acetylcholinesterase.  In a previous post, I described how the transmission of nerve impulses occurs, describing how those impulses travel across synapses in the form of chemicals called neurotransmitters (here).  What I neglected to mention was that after the signal has been conducted, the neurotransmitters need to be removed from the synapse, or else the post-synaptic cell will be fooled into thinking that another impulse has been transmitted, and another, and another, indefinitely, until the neurotransmitter molecules are gotten rid of.  Some neurostransmitters, like serotonin, are reabsorbed by the presynaptic cell.  Antidepressants like Zoloft and Prozac work by preventing this reuptake, thus increasing the activation of cells responsive to serotonin. In the case of another neurotransmitter called acetylcholin, the molecules get broken down by the enzyme acetylcholinesterase.  Acetylcholine is primarily used by the neurons that allow your brain to control muscle movements.  Blocking acetylcholinesterase from breaking down acetylcholine in synapses can lead to continued muscle contraction.  Which may not sound so bad until you realize that this is actually the mechanism of action of another organophosphate/cholinesterase inhibitor: Sarin "Nerve" gas.  Sarin is a very potent acetylcholinesterase inhibitor that causes its victims to convulse wildly, often dying from suffocation as the diaphragm and accessory muscles involved in breathing contract uncontrollably preventing the victim from taking in sufficient air.  Now, I know that's scary, but, despite being organophosphates and cholinesterase inhibitors, malathion and diazonin are not nearly as potent as Sarin gas, and like I said, in low doses, malathion is actually quite harmless to humans (unless you eat or drink it at high concentrations).  Diazonin, while still far from lethal, is a little more caustic, and has been banned by the EPA for residential use, (though it can still be used for agricultural use).  Now, if you still want to buy some pumpkins from the store (or already have), the good news is that they were likely mainly treated with malathion, BUT, if you have some really GIANT pumpkins, they were probably treated with diazonin (or both diazonin and malathion).  In order to get giant pumpkins, you have to leave them in the field longer... the longer they're in the field, the more likely bugs are to camp out and have a good meal, thus, in order to grow large pumpkins, insecticides like diazonin must be used.  Of course, by buying these pumpkins you are supporting the widescale use of these chemicals which can cause damage to the nervous systems of lots of smaller animals like birds and rodents who might raid the pumpkin patch for a meal, or fish and amphibians who may be getting higher doses of these chemicals in the water runoff to streams and ponds.  So while the "Great Pumpkin" may not be real, the real pumpkins at your local grocer can be just as scary.  By the way, the cartoon comes from http://shinjiku.deviantart.com/ , I hope the artist doesn't mind my swiping it for this post.

We live in exciting times! Blindness cured!

Well, not exactly, but some sensationalism is warranted.  This is mostly a follow up study that has been ongoing for the past 2 years or so, but researchers from UPenn and the Children's Hospital of Philadelphia have successfully used gene therapy to reverse (for the most part) the visual impairments associated with a disease known as Leber's congenital amaurosis, or LCA.  To be clear, this is not a cure for all types of blindness (that is, blindness due to other causes), nor is it even a full cure for LCA, as none of the patients have regained completely normal vision (though they have made tremendous improvements), and the mutated gene targeted in this study only accounts for 8-16 % of all LCA cases.  Still, this is incredibly promising research, for several reasons.  First, and most obvious, despite not being a complete cure, a single injection of a gene therapy mostly reversed LCA associated blindness to the point where half of the patients are no longer legally blind and can even navigate obstacle courses in low light conditions.  The second major aspect of importance is the gene therapy itself.  In this case, an adeno-viral vector was designed to insert a functioning gene (called RPE65, or retinal pigement epithelium-specific protein that weighs 65 kilo-Daltons) in place of a mutated version that underlies LCA in a small proportion of cases.  What's amazing is not the virus mediated transfection of the gene, as this is a technique that has been around for a while, and used successfully many, many times in mice and other experimental animal models.  What's exciting about the use of this technique in humans is that the FDA is very very cautious when it comes to allowing it to be used on humans.  Mainly, they are concerned because a virus is used to carry the gene and insert it into human cells, and they are also concerned that, in the long term, messing with the DNA in the cells could increase the risk that the infected cells will become cancerous.  Of course, the viruses used in gene therapy have been engineered so that they cannot replicate, and therefore cannot cause disease (much like attenuated viruses that are used in vaccines).  But the worries about cancer can only be alleviated when we have a large enough group of patients who we can follow over time to see whether or not they develop any tumors.  As mentioned, this particular study is already 2 years in the making, and, so far, there does not appear to be any increased incidence of cancer, which is very exciting and promising (though, of course, these patients will still need to be monitored as the years go by).  Finally, the fact that these viral mediated gene therapies have been used and validated so extensively in lab animals is what made this therapy possible (and successful) in humans.  Thus, another major underpinning of this study is how it demonstrates the importance of lab animal use in biomedical research. 
I also liked how the researchers used each patient as their own control by injecting the therapy into only one eye.  In this way, they could compare their results from the treated eye to the untreated eye, and since both eyes are in the same patient, they should be as close to identical as possible including the amount of bloodflow they receive, etc.  In this way, the researchers could be sure that it was really their treatment that made the patient's eyesight better, and not a natural regression of the disease (or a miracle).  They can tell this because if one eye gets better and the other doesn't (assuming it's the treated eye that gets better) then the gene therapy appears to work.  If both eyes stay the same, or get worse at the same rate, then the therapy didn't work.  And, if the treated eye actually gets worse faster than the normal rate of degeneration due to the disease (which should be evident in the untreated eye), they will know that there is something wrong with the treatment.  Of course, this type of design makes it difficult to rule out any placebo effect (since, I'm assuming, the patients all know that at least one eye is going to be receiving the treatment), but given the remarkable results, I think we can rule out the placebo effect, or, if not, apparently, we can use it to reverse certain types of blindness.  Either way, I think we should be happy.

The cerebral cortex is not in the neck.

Here's one that simply amazes me.  Someone brought this to my attention a little while ago, but it took me some time to track down.  In the tv show "The Unit", one of the members of this secret counterterrorism group gets killed.  His name was Hector, and I guess it was a big ratings ploy in season 3 where they leaked that someone from the unit was going to be killed. Hector was shot through the neck by a sniper, and the bullet ultimately winds up being lodged in his chest cavity somehow.  Ignoring the fact that the bullet made a magical U-turn to end up where it did, I am more perplexed by the scene in the show where the medical examiner tells one of the other members of the unit that "the bullet entered the neck here, snapping the cerebral cortex.  He felt no pain."  In the scene, the guy even points to the cervical portion of the spine (the neck) as he is saying the phrase "snapping the cerebral cortex".  I hate to break it to the writers of "The Unit", but the cerebral cortex is in the brain, not in the spinal cord.  Sort of like an onion, the brain has several layers, except, unlike an onion, the brain tends to be bigger and more squishy and wrinkly.  Just like the tough outer skin on the onion, the brain has a tough protective skin called the dura mater (which basically means "one tough mother", dura is the latin word from which we derive the word durable, and mater, means mother, like in alma mater, which means "nourishing mother", a term we honor our colleges and universities with since they nourish us with scholarship).  Under the dura mater is the arachnoid layer which doesn't really resemble anything you'd see in an onion, but looks more like a collection of spiderweb-like structures (thus arachnoid) which helps to cushion your brain against collisions with the inside of your skull.  Beneath the arachnoid lies the pia mater ("soft mother"), and, together, these three layers make up the meninges (which may sound familiar if you've heard of meningitis, which is an infection characterized by the swelling of the meninges.  Meningitis can be bacterial or viral, and in some cases, usually when it is bacterial, meningitis can be fatal, which is usually when it shows up in the news).  Directly under the meninges lies the cerebral cortex.  It is the outermost layer of what we typically think of as the brain: the gray, wrinkly ball that sits in the skull.  The cerebral cortex is actually the part of the brain that gives it its gray and wrinkled appearance, and it is also an area that is very important in most of our thinking, feeling, and doing.  The image below gives you some idea of the cerebral cortex, though it might be a little tough to read, I recommend going to the site I took it from: http://www.coheadquarters.com/coOuterBrain1.htm to get a better look.  Once you get below the cerebral cortex you hit subcortical structures like the basal ganglia (of which, the striatum is the largest portion), and even the cortex itself is subdivided into many layers (6 in the human brain).  Though, unlike an onion, or the picture, most of these layers are not so easy to pull apart, and they are more distinctions that have been made by looking at the tissue under a microscope than an onion like layering.  All of that being said, I'm not saying that getting shot in the neck wouldn't kill you, especially if it severed the spinal column, and, if that were the case, then it is possible that you wouldn't be in much pain (at least you probably wouldn't feel much below the point at which the spinal cord was separated), but I think you're cerebral cortex would remain intact.

Society for Neuroscience Annual Meeting

I'm off to Chicago for the next 5-6 days for the annual meeting of the Society for Neuroscience (along with some 30,000 other neuroscientists).  I realize that I have not been posting a lot lately (I am working on a couple of papers that have been demanding most of my time) and now with the conference I will likely continue to be absent.  But, hopefully, when I come back, I will have lots of cool new stuff to talk about.

Booth loves Bones.

So I was watching an episode of the Fox television show "Bones" a while back (I have yet to check out any of Kathy Reichs' books, she is the forensic anthropologist/author who is the inspiration for and producer of the show, but I do enjoy the show, and the overly rational, though exaggerated to the point of caricature, Temperance Brennan, a.k.a. "Bones").  Anyway, the other main character in the show is Booth (played by David Boreanaz), an ex-army sniper turned FBI agent who investigates murder cases with "Bones" and the rest of her forensics team.  Recently, Booth was diagnosed with a brain tumor and underwent surgery to have it removed, during the recovery, he was in a coma and dreamt that he was married to, and madly in love with, Bones.  Upon fully recovering, his amorous feelings followed him out of the dreamworld and into reality.  As evidence for the fact that Booth did, in fact, feel like he was in love with Bones, the FBI psychologist Dr. Sweets (played by John Francis Daley, who you may remember from the excellent, but short lived series Freaks and Geeks) shows Booth PET scans of his brain showing "activity" in the VTA, or Ventral Tegmental Area.  PET scans are somewhat similar to MRI scans, and if you follow the posts, I've described how fMRIs work in the past, but again, briefly, fMRIs measure bloodflow in the brain. When a particular area is being used, it needs more oxygen and glucose, thus, more blood.  But, here's the catch, everywhere in your brain needs oxygen and glucose, so a single MRI image wouldn't really tell you very much.  What you need to do is get a baseline, and then, while changing one thing (asking the person to think about something specific or to perform a specific task), you take another image.  When you subtract everything that is the same out of the two images, and look only at what is different, you get a functional MRI (fMRI), that is, an image showing exactly which areas of the brain seemed to be working harder while you were trying to do that specific task.  PET scans (or positron emission tomography) work in a similar fashion, except instead of measuring the iron (or oxygen) in the blood, PET scans work by measuring glucose (which has been tagged with a radioactive fluorine molecule to show up in the scan).  But the same principle holds if the PET scan is to be specific to a function, you have to have one image as a baseline, and another for the test condition.  In the case of Booth, I don't dispute that thinking about the one you love leads to increased bloodflow in the VTA and the caudate, There are several studies suggesting these 2 areas are involved in romantic love.  (One such study can be found here, or, for the popular press version, here.)  No, what I dispute is that a single PET scan image of Booth's brain would not likely show the VTA and caudate to be working overtime, unless Booth was specifically thinking about Bones while the scan was being done.  And even then, you would really only get an image like the one they showed if a baseline image had been taken.  A minor point I know, but when neuroscience comes up on a popular tv show, I can't help myself but to comment.  Actually, despite the minor error, I have to commend the producers and writers of Bones for introducing some pretty cool and pretty recent neuroscience info into the show.
And if you find it interesting too, here's a little more fodder for your brain: in many of these studies, for both the VTA and the caudate, it tends to be the right side of the brain that lights up, leading us to wonder what the VTA and the caudate in the left side of the brain are doing.  (And if you think that makes sense because the right side of the brain is supposedly the creative, artsy, and romantic side and the left brain is the rational side, you may have a point, or you may find a post about whether or not all that right brain/left brain stuff is really true sometime in the near future).  The really interesting conclusion of these studies however is that they suggest romantic love (as opposed to familial or brotherly love or platonic love, i.e. friendship) derives from motivational areas of the brain, not the ones involved in emotions like joy or sadness.  So, while relationships involve their fair share of joy and sadness, apparently falling in love is more like becoming addicted to cocaine...

By the way, if you're wondering why I didn't talk at all about Booth having visual hallucinations from a cerebellar tumor, it's because it is within the realm of possibility.  Though visual hallucinations are more commonly associated with tumors or lesions in the occipital lobe (in the back of the brain, where the visual cortex is located), they can occur in patients who have cerebellar tumors.  Though rare, cerebellar tumors can lead to visual hallucinations due to the fact that the cerebellum is also in the back of the brain, and a large growth can put pressure on the occipital lobe which is right next door.  Though, the more interesting thing is that Booth's hallucinations were actually visual and auditory, as he could hear and converse with his hallucinations, this is even more rare, as auditory processing occurs in the temporal lobe which is a little further forward in the brain, and auditory hallucinations are most commonly associated with tumors located there.  Just like the occipital lobe is heavily involved in visual processing, and the temporal is heavily involved in auditory (or hearing), the cerebellum is involved in motor movements, particularly those that require coordination (like running or playing sports).  As such, most cerebellar tumors are associated with "ataxia" which is the loss of coordinated movement in the limbs, often this is revealed by an unsteady gait or falling forward or to the side when walking, or by clumsiness when performing tasks that require coordinated movements of the hands or feet (see http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed6.section.19621 for more symptoms of brain tumors).  It is odd that Booth wouldn't show any of these symptoms, and only have the much more rare hallucinations, but it is not impossible.  Everyone is different (and every tumor is different) this is what makes medicine (and finding a cure for cancer) so difficult, and while it is unlikely that a patient with a cerebellar astrocytoma would present with only the symptoms of having visual/auditory hallucinations, it can (and sometimes does) happen.

Communicating Science

This is a big problem in science.  There appears to be a big disconnect between the general public and science and scientists these days.  Books are being written on the subject (and many a blog) and many people are concerned that the reason you still have half of this country believing in creationism rather than accetping evolution as the origin of man (and the rest of the species with which we cohabitate on this planet), or why people don't believe that global warming is real, etc. etc.   Another example of this is NASA's latest project, where they crashed a rocket into the moon to look for ice/water under the surface.  The idea was great, and elegant in its simplicity, slam a rocket into the lunar surface, and see if it turns up some ice in all of the dust and dirt it blows up into space.  (Kind of like when you throw a rock into a pond and water splashes up, the same thing happens if you throw a rock into a pile of sand, and, when you slam a rocket into the moon).  The associated press ran an article about the experiment which, when viewed live yesterday, was, well, unimpressive to the naked eye.  The article is actually pretty good, and I myself was expecting a little more when I watched the video footage (given what I had seen in NASA's computer simulations, and its prediction of a 6-mile high plume of dust and dirt).  If you read the article, they quote heavily from Michio Kaku who is an excellent communicator of science, but there's also a comment from Alan Stern: The mission was executed for "a scientific purpose, not to put on a fireworks display for the public," said space consultant Alan Stern, a former NASA associate administrator for science.  This is a problem, I understand that rarely is science done to be a spectacle for the public, but when it is touted to the degree this mission was, and the public is obviously and readily excited to see a science experiment in progress, you shouldn't be so quick to dismiss them when they are disappointed.  You should, like Kaku did, explain why those expectations weren't met, but why there is still lots of reasons to be excited about the experiement and about what we might find out.  I mean, in this day and age of instant gratification, science is becoming less and less popular because it takes time.  Most people have no idea that it will probably be another month before we get all of the data from this mission analyzed (i.e. before we can have an answer to whether or not water is on the moon).  And even if the experiment worked perfectly, we may still not have a complete answer.  This is the nature of science.  It takes time, and it is an intensive process.  When you have the public's interest, you should maximize the opportunity and take advantage of the "teachable moment".  The public understands that NASA didn't crash a rocket into the moon simply for their viewing pleasure, but they were interested none the less.  Capitalize on that interest, explain why you are crashing a rocket into the moon, and why it's so important, and maybe, the next time a senator has to vote on how much funding NASA is going to get, he or she can vote for a funding increase, and rest assured that the taxpayers' money is going to good use.
And by the way, finding water on the moon, in the words of Michio Kaku would be more valuable than finding gold.  From the water, we could get hydrogen for rocket fuel, oxygen to breath, and of course, water to drink and grow food, making the idea of putting a livable colony on the moon a more feasible possibility (and a LOT LESS expensive).  It would also help with our basic understanding of the composition of large bodies in our solar system and universe and give us an idea of how rare (or how commonplace) water is in the universe.  Important stuff.

More support for glia, less for the neuron doctrine...

This story is a little bit old, but just another interesting example showing how important glia are, not only for neuronal function at the cellular level, but, they are directly involved in important behaviors, like avoiding smells that could mean danger, or seeking out those that mean food.  Anyway, here's the story: http://www.sciencedaily.com/releases/2008/10/081030144624.htm I would write more, and I have lots of other topics/posts to get up, but I am really busy with a couple manuscripts and research (and the SFN conference is coming up) so this will have to suffice for now.