Zombie cockroaches

Just when you thought the zombie apocalypse couldn't get any worse... now we have roaches to worry about!  Fortunately, zombie roaches in the wild are not aggressive, brain-sucking insects. It turns out that the wasps that make the zombies are what we should really be concerned about.

Jewel Wasp (A. compressa)
Image courtesy of Morphbank.net

The Jewel Wasp (Ampulex compressa) has an elegant and extremely sophisticated method to secure a good home for its eggs.  It attacks and injects a cocktail of neurotransmitters into the brain of a roach, effectively turning it into the slave of the wasp (Educated Earth has a good video of this process, see here).  The wasp then drags the roach to a suitable location and lays its eggs in the abdomen. The roach is hypokinetic for several days until the larvae hatch and then they slowly consume the host.  Interestingly, the larvae eat the internal organs in a way that maximizes the lifespan of the roach.  It's a morbid process, but how the wasp achieves this zombification is truly incredible.

The wasp actually stings the roach twice.  The first sting is to the thorax and produces a mild and very transient anesthetic that paralyzes the front legs.  A study by Moore et al. (abstract) showed that the active components of the first sting activate GABA receptors (GABA itself, and receptor agonists beta-alanine and taurine).  During the minute or so of action, the wasp then stings the roach again, but in a very precise location within the brain.  In a sense, the wasp is acting like a brain surgeon, who needs their patient to remain still while a precise operation is done.  This second injection is a cocktail of neuroactive compounds that have very specific effects on the roach's brain.  After the anesthetic wears off, the roach grooms itself excessively and then becomes lethargic.  It is not paralyzed, just sluggish.  When the first studies on A. compressa were done, there was a great deal of controversy over whether the venom was delivered to the central nervous system, or directly to the site of action in the brain.  In an elegant study by Haspel et al. (abstract), they milked the venom from wasps and injected them with radiolabeled carbon (14C).  This meant that the fresh venom produced by the wasp would contain the radiolabel.  Haspel could then visualize the location of the venom in the roach brain by taking pictures of brain slices.  Those of you who think that would be cool as hell, raise your hand!!

  Anyhow, it was found that the neurotoxin attacks the brain directly, with the most venom at the supra-esophageal ganglia (SupEG) and the sub-esophageal ganglia (SEG).  In insects, these areas are thought to provide "higher order" brain function.  A recent study by Gal et al.(abstract) found that the venom affects the drive to initiate and maintain walking.  Other motor skills (like flying, swimming, self-righting) were not affected.  Based on the electrochemical difference between stung and unstung wasps, they concluded that stung wasps had a deficit in the ability to "reach a decision" to walk.  There must be human versions of this wasp because I swear, there are days when I have trouble reaching the decision to get off the couch.

A follow-up study by Gal et al in 2010 (PLoS article) made another very interesting discovery.  Roaches who had their brain ganglia removed were stung for a much longer period of time (196 sec) than normal roaches (39 sec).  Why?  Because the wasp was actively seeking this part of the brain and couldn't find it!  What does it search for?  A specific morphology?  A defined depth within the brain?  Nobody knows.  Furthermore, why is it so important for the wasp to target this region so specifically?  The answer is also still open to speculation but this has zombie written all over it.  The wasp needs the roach to be compliant to move it into the proper position for incubation of the larvae, but resist the urge to flee for several days.  So, the venom basically takes away whatever "freewill" the roach might have had.

Octopamine
 (image courtesy of Wikidocs)

So, what is this supernatural cocktail?  Not a whole lot is known about the composition of the venom (another great project for biohackers or kids looking for obscure science fair projects). I will post more details later but one key component appears to be an antagonist of the octopamine receptor.  Octopamine is a monoamine neurotransmitter that is specific to invertebrates and OA levels are known to be associated with the hypokinetic state.  Several years ago, Rosenberg et al. (abstract) gave roaches a octopamine receptor agonist and found that motor activity in stung subjects was at least partially restored.  Other receptor agonists and antagonists had little effect.  This is certainly one clue about how A. compressa makes zombie cockroaches but for now, the rest of the process is all voodoo.

Resveratrol: One step forward, two steps back

Resveratrol is in the news again but this time for all the wrong reasons.  No, it didn't just break up with a pop star or get busted for breaking probation.  Stunning allegations from the University of Connecticut suggest that a significant percentage of Dipak Das' (UConn professor and Director of the Cardiovascular Research Center) scientific research on RES may suffer from scientific fraud (see here for just one article).  I looked at some of the (60,000 page!) report and it looks like much of the fraud was based on images of Western blots that had been altered or fabricated.  I have long complained about figures of Western blots in various publications where only the bands of interest are shown with no molecular weight markers or anything.  This is like buying a car based on a picture you see on the internet.  Yes, there is a band there but you have no idea how good the antibody is that you are using to probe with, if the protein runs at the right place on the gel, etc.  In Das' case, it looks like random bands were just pasted on there.  No bueno, pal, no bueno.

Does this mean that resveratrol is now demoted to a worthless contamination in an otherwise tasty glass of wine?  Um, no.  I'll admit I have read some of Das' stuff and it has influenced some of my opinions about RES, but there are a whole host of researchers out there that have demonstrated how RES impacts biological pathways and (in my opinion) there is very clear evidence that it has a significant effect if the dose is high enough.  Unfortunately, cases like this place a stigma on research involving RES and could hinder progress towards understanding the physiological benefit of this molecule.

Ok, so now on to better news.  My favorite wine goddess maker, Kerith Overstreet from Bruliam Wines, has a new blog post on the cardioprotective properties of wine. It's pretty funny (you can check it out here) but in it she highlights not RES, but oligomeric proanthocyanidins (OPCs).  If you recall an early post I made on the magic of winemaking (here), you may recognize OPC as another term for polymerized flavinoids, which include tannins such as catechin.  Most OPCs originate from the grape skin, so the amount of OPC in any given bottle can vary dramatically.  The final levels depend, in part, on how long the grape skins are left in the fermentation since it is the rising alcohol content that ultimately extracts the monomeric proanthocyanidins from the grape.  Therefore, craft is a big variable in determining the benefit of wine to the drinker (we are all counting on you, Kerith!) Interestingly, Das was involved in a company called Dry Creek Nutrition, that was trying to purify and sell proanthocyanidins.  In light of the Das debacle, maybe OPCs are the new RES!

Discovery of an upside down, carnivorous plant in Brazil

I've always been a fan of carnivorous plants.  Pitcher plants, Venus flytraps... very cool.  An article just published in PNAS describes a very bizarre plant that has been recently characterized as carnivorous.  The flowering plant, from the genus Philcoxia, is a pathetic specimen.  Found in dry savannas of the cerrado in central Brazil, the stems are leafless, which means it resembles many of my potted plants here at the house.

It turns out that the leaves of Philcoxia are actually underground! Most plants would find this adaptation ridiculous.  The primary function of a leaf is to capture sunlight and produce energy through photosynthesis.  What kind of freakish plant would put the leaf underground where there is no light?  A murderous plant, of course.

What Pereira et al. show in the PNAS paper (abstract) is that the leaves of Philcoxia have evolved to trap and eat nematodes in the soil.  The data to support this comes from an elegant study using nematodes that had been fed nitrogen-15 (15N), an isotope of natural nitrogen.  Releasing the nematodes in the vicinity of the plant, they measured the change in 15N in the leaves after two days.  They show that the absorbed 15N increases from nearly undetectable levels before the experiment to about 15% of all nitrogen content by Day 2.  They talk in the methods about how they extensively washed and dried the leaves to remove all traces of 'nematode remains', but the greatest risk in this experiment is that the 15N they are measuring is simply from the residue of dead worms on the leaves.  Nevertheless, they also show that the leaves are covered  with a sticky sap and that enzymes on the surface are available to break down the corpse for consumption, as found in other carnivorous plants. Interestingly, the glands that produce the sap are also similar to those found on other carnivorous plants.  So, it certainly seems plausible that another plant has found its way to the dark side.  Better call NCIS (that's Nematode Criminal Investigative Service).

Maybe I'll just start telling people that the dead plants I have around my house are rare Philcoxia from central Brazil and that they are supposed to look dead.  Maybe I'll tell them that I have re-engineered them to eat, um, larger prey. I wonder if carnivory could be engineered into grass?  That would keep the neighbor's dog off of the yard!! Ahh, the possibilities...

Bioluminescent Light Bulbs?

There is a news blurb going around about using flasks of bioluminscent bacteria to light your house.  I mentioned this type of thing in the Foxfire post, but Philips has been working on this for some time.  The lighting system consists of a wall of hand-blown glass flasks, coupled to methane lines that are sourced locally (ie, from the users trash).  The bacteria have been engineered to glow when methane is present, so users can control the lighting.  Although this is impractical for general use at the moment, it is probably the beginning of the next revolution in lighting. Some of the articles talk about the most likely first application, which would be for safety lighting near buildings or on roadways.  I think it would be cool to have trees or shrubs engineered to glow as well... it would be awesome to have glowing bushes near our front walkway!  If you want to see how the bioluminscent bacteria fit into the Microbial Home, see the link at Philips' web site ( link), it's pretty trippy stuff.  If you want to try your hand at growing bioluminescent algae at home (or for a cool science fair project!), here is a good starting place (link).  If you want to see what a team from Cambridge University did for their iGEM project last year (hint: it's on making bioluminscent products) check out this link.

  Philips is not the only company looking at commercializing bioluminescence for non-medical applications.  A company called BioLume (link), based in Research Triangle Park, NC is trying to put bioluminescent proteins in food.  Yeah, that's right.  Glowing food.  They use examples like candy and alcohol as likely products, as well as makeup.  Sounds like a Rave Gone Wild! The company has IP around many different bioluminescent proteins (mostly luciferases) found in marine life.  I imagine that they formulate it in a way that the enzyme becomes active when there is a change in the environment.  They mention a calcium-induced reaction of a enzyme-substrate fusion, as well as fusions with fluorescent proteins.  I'm sure that the proprietary chemistry and photophysics involved in these products is really cool!  I do hope the metabolized product is non bioluminscent... there is nothing more scary that glowing pee!

Red wine in a pill: Metabolic effects of resveratrol in humans

Remember back in July I talked about a future where simply popping a couple of resveratrol tablets gave the same benefit as a walk around the block?  That future may be closer than we think!  A recent paper in the journal Cell Metabolism describes the results of a very small study of resveratrol in humans and the data is pretty exciting.  Let me repeat that caveat... this was a small study!  Still, the metabolic effects described in this work clearly emphasize the need for further research on this and other magical polyphenols.

The paper published by Timmers et al. (abstract) is the first to study the metabolic effects of resveratrol (RES) in a clinical setting.  Eleven obese men were given either RES (at 150mg/day) or placebo for 4weeks, followed by a 4-week washout and then the treatment was switched (this is known as a crossover study).  Patients and doctors were both blind as to what treatment was being administered and during treatment, a variety of metabolic tests were conducted.  There is a lot of data in the paper (and it looks like the pdf is free, so check it out yourself!) but let me hit a few highlights:

1) Patients taking RES show an increase in mitrochondrial efficiency, particularly in fatty acid oxidation of muscle fats, and decreased levels of triglycerides and glucose levels.  Significantly, these changes are seen at the gene level, suggesting that it is the overall metabolic pathway that is improved, not just a downstream clearance of metabolic markers.  A similar pattern of changes has been noted in athletes undergoing endurance training (they reference Dube et al, 2008 and Meex et al, 2010).  This is fairly consistent with the Momken paper I blogged about back in July, ie, RES acts like an exercise mimetic.

2) Changes in glucose and insulin levels are modest.  Timmers et al. report a statistically significant drop in serum glucose and insulin levels in the patients taking RES, but this effect is pretty modest.  There is also a shift in peak glucose and insulin levels after a liquid test meal, suggesting some changes in glucose homeostasis, but they could not draw definitive conclusions.  If you recall, the rat data from Momken et al. was also pretty weak with regard to insulin/glucose levels.

3) RES also showed other health benefits:  This study also demonstrated a significant effect of RES on lowering systolic blood pressure and mean arterial blood pressure, as well as decreases in resting energy expenditure and sleeping metabolic rate.  The later two effects are also seen in studies of calorie restriction and further illustrate the metabolic changes induced by RES.  Calorie restriction is also associated with increased lifespan in animals, so these observations may be pointing to another possible health benefit of RES.  They also observed a decrease in markers of inflammation, further suggesting an overall improvement in health. Although this is interesting, I still think the catechins are the more potent player here... I'd like to think that as the flavinoids polymerize during aging, the wine gets better and better for your heart. It would be interesting to see how some of these molecules perform in a study similar to this.

Taken together, this paper highlights some of the metabolic effects of RES in humans and may offer some insight into the health benefits of this polyphenol.  Much like the rat study, however, this is a very high dose (the equivalent of >100 glasses of wine per day) and so who knows if there are long term side effects at this dose.  The fact that they see statistical significance with only eleven patients is also very surprising.  Clinical studies usually need hundreds, or even thousands of patients to provide enough statistical power to draw conclusions like this.  Personally, I would find taking a pill much less satisfying that enjoying a nice glass of Cabernet. Since that glass of Cab is a veritable grab bag of Redox goodies, I think it is also very likely that there are many other 'good' polyphenols in wine that scientists haven't studied as rigorously as RES.  So as dozens of trick-or-treaters descended upon our neighborhood on Halloween night, I had to raise my glass to our ancient ancestors who discovered the wonderful winemaking process, and the scientists who now try and tease apart how it does what it does. I may have also stolen a chocolate or two... in the interests of science, you know.

Halloween winemaking magic at Bruliam Wines

Just in time for Halloween, Kerith Overstreet at Bruliam Wines has a great blog post this week about working with her spooky 2011 harvest (beating it into submission, actually).  Sounds like a challenging year!  She describes the redox chemistry that goes on during the early fermentation process and actually has a graph from her lab!  I first blogged about the magic of winemaking after Kerith's great talk on the subject (here is my post) and even she refers to the process as magic in her latest post (but she also refers to wife swapping, Alanis Morissette, and Hanukkah miracles, so who knows what state of mind she was in as she wrote this).  Anyhow, a very fun, informative read directly from the mysterious front lines of winemaking.  Enjoy it with a glass of good Cabernet, the official wine of the dead.

Keriths latest blog post:  (link)

21st Century mummy

Just a quick pointer to a cool article on a recent attempt at mummification (here's the link). Stephen Buckley, a chemist at York Univeristy in England, has spent two decades studying how ancient Egyptians made mummies.  He studied tissue samples and chemical traces left on canopic jars in an effort to reproduce the method.  He then tested the process in his shed, using pig's legs as a proxy for human flesh (there's a DIYbio project for you!).  I'm not sure if this guy is married, but even here in the Dark Lab, this work would be pushing the limits.  Anyhow, this year he felt that he was ready for prime time.  He placed an ad looking for suitable volunteers and the lucky person was... Alan Billis, a London cab driver.  Terminally ill with lung cancer, he went through the mummification process after he died. By all accounts, it was a success and the body will be kept for at least a year to study.  Hopefully, Alan is hanging out with a bunch of cool, Egyptian princesses.  Thousands of years from now, archaeologists will argue over whether our society placed a high value on cab drivers, or if Mr. Billis was simply a member of the ruling elite.  They will come up with grand theories on how he lived, how he died, and why he was the only surviving mummy of the period.  Should make for an interesting read.



Cat mummy at the British Museum (link)



To me, it is truly amazing that with all of today's technology, it is difficult to reproduce the mummification procedure.  The Egyptians likely had years of empirical data to build from and since it was considered a sacred ritual for the upper class, there was significant motivation for young priests to be good at making a mummy.  I can see a room full of young mummification interns, trying to preserve rats or some other suitable test animal.  After months of work, the mentor unwraps the package, only to find a rancid, decomposing corpse. "Aw, man," the student whines (or whatever the angsty teen expression was at that time).  He then slouches his way over to the stone quarry.