Category Archives: Physiology

Carnal Carnival – everything you ever wanted to know about poop you will be able to learn in ten days from today

When people tweet on a late Saturday night, strange things can happen, including this – foundation of another science-themed blog carnival: The Carnal Carnival! Yup, it already has a homepage, and a list of hosts for 13 months in advance, and even a Twitter account.

What is The Carnal Carnival? A monthly collection of best blog posts covering, mostly from a scientific perspective, a variety of bodily functions, fluids and excretions that are usually not discussed in polite company over an elegant meal. But it is science! And it is important! And it is fun! And there is nothing that the Web has not already seen yet, as far as inappropriateness goes, so why not add some sense and some scientific rigor to these topics so people who search for strange words on Google end up actually learning something.

I volunteered to host the very first edition, here on this blog on August 20th in the morning, so you only have ten days to send in the entries.

The topic of the month is Poop! Yes, feces, excrement, frass, scat, droppings and everything about it. Let’s put together a complete online guide to every possible aspect of the topic, all in one place. Need ideas? Here are some:

How do you look for scat out in the field? What can it tell you: what animals are there, how many, where they are moving (perhaps tracking poop trails by satellite), what they are eating and how their digestive systems work? How about insect frass?

How and why various parasites use animal droppings as home during parts of their lifecycles? And what are dung beetles really doing?

Why some animals require time and privacy to poop, circling around, adopting un-natural postures, then straining (e.g., dogs, humans), while others can defecate on the run (have you seen horses pooping in mid-flight during jumping competition)? Penguin projectile pooping?

What determines the shape of the droppings? Why cows make pies, dogs and humans eject sausage-like objects, elephants and horses produce several large spherical droppings, while goats and rabbits make many little spheres? What determines color and smell?

What are the differences in anatomy and physiology of the large intestine in various vertebrates? How does a colon extract all that water from the digested material? Does that mechanism differ in animals that live in deserts and produce very dry poop versus animals that do not need to conserve water that much?

What is the physiological mechanism of defecation? What drugs and chemicals can affect it and how?

Paleontology and physical anthropology: what can we learn about extinct animals and ancient humans by studying coprolites?

Medicine (and veterinary medicine): when stuff goes wrong: causes and treatments of gas, excessive flatulence, incontinence, impacted colon (and cecum in horses), diarrhea, etc.

One word: coprophagy!

What is the best position for humans during the act of fecal excretion?

Anthropology, archeology and ethnography: historical and geographical differences in attitudes toward human (and animal) excrement.

Technology: from doing it in the woods to burying in holes in the ground to open pits to outhouses to squating toilets to sitting WCs to high-tech gizmos that sing to you and diagnose diseases from your poop. How do astronauts do it in zero gravity?

More technology: history and geographical variation in methods for getting rid of human waste. Comparative study of sewers of Great Cities.

Agticulture, environment and epidemiology: use of animal and human waste as fertilizer. Environmental effects of human waste and hog lagoons. How does fecal matter get into the food system and what can happen then? Open communal pits as sources of disease.

Have you read fiction, non-fiction or poetry that focuses on some aspect of poop? Review it!

If you have already written blog posts on these or related topics, send them in – old posts are welcome. If you have not, but have interest or expertise in something like this, you have ten days to send the permalinks of your posts to me at carnivalcarnal AT gmail DOT com (or, this month only, to Coturnix AT gmail DOT com).

If you have posts on other topics concerning strange bodily functions – check the schedule of hosts and topics for the next year and send the appropriate posts at appropriate times.

Books: ‘The Poisoner’s Handbook’ by Deborah Blum

Poisoner's Handbook cover.jpgIf you picked up The Poisoner’s Handbook (amazon.com) looking for a fool-proof recipe, I hope you have read the book through and realized at the end that such a thing does not exist: you’ll get busted. If they could figure it all out back in 1930s, can you imagine how much easier they can figure out a case of poisoning today, with modern sensitive techniques? And if you have read the book through, I hope you found it as fascinating as I did. Perhaps you should use your fascination with poisons to do good instead, perhaps become a forensic toxicologist?
My SciBling Deborah Blum (blog, Twitter) has done it again – written a fast-paced page-turner, full of action and intrigue, and with TONS of science in it. It reads like a detective novel. Oh, wait, it is a detective novel. Who said that an author has to invent a fictional detective, an Arsene Lupin or Hercule Poirot or Sherlock Holmes or the Three Investigators? There existed in history real people just like them, including Charles Norris and Alexander Gettler, the heroes of The Poisoner’s Handbook.
Charles Norris was the first Chief Medical Examiner of the City of New York, or at least the first one who was actually qualified for that position which, before him, was a political appointment not requiring any expertise. Norris served in this role from 1918. to 1935. and revolutionized both the position and the science of forensic medicine. Alexander Gettler was one of his first appointees, who served as New York City’s chief toxicologist until 1959.
The two of them used their prominent position to set the new high standards for the profession of a public medical examiner, and also set the new high standards for the scientific research in forensic pathology, including forensic toxicology – the study of the way poisons kill and how to detect it. They affected rules and legislation with their work, they sent clever murderers to the electric chair, and exonerated the innocents who were headed that way due to mistakes of the non-science-based courtroom battles. And in order to do that, they needed to do a lot of their own research during many years of long days and nights in the lab performing meticulous and often gruesome studies of the effects of various substances on animals, people, living and dead tissues and coming up with ever more sensitive and clever methods for detecting as small quantities of the poison as was technically possible at the time.
In the author’s note at the end of the book, Deborah Blum notes that there were many other forensic scientists before, during and after the Norris-Gettner era, and many of them got mentioned in the book or are cited in the EndNotes (which I discovered only once I finished the book – I hate the way publishers do this these days!). But it is also true that Norris and Gettner were the leaders – they used their prominent position and political clout, and their meticulous research defined the high standards for the nascent discipline. In a way, the central importance and prominence of these two men worked well for the book – here we have two interesting characters to like and follow instead of a whole plethora of unfleshed names. And as each chapter focuses on one poisonous substance and one or two notorious cases of its use, it is just like following Holmes and Watson through a series of Sir Arthur Conan Doyle’s stories – the two characters are the connecting thread, and they evolve throughout their lives and throughout the book, case by case.
Apart from being a history of forensic toxicology, the book has several other themes that keep recurring in each chapter, as they chronologically unfold. The book is also a history of 1920/30s New York City, and a history of technology and engineering. Carbon monoxide poisoning? That was the beginning of the car craze. Gas? Everyone cooked and heated with it at the time. Some other poisons were easily found in many over-the-counter products in stores and pharmacies.
Having just read On The Grid, I was also attuned to the discussions of infrastructure of NYC in the early 20th century. How did people transport themselves? Air pollution? Gas? Clean water? Wastewater? All sources of potentially toxic chemicals. How efficient was garbage collection? Not much….thus there were many rats. And rats needed to be controlled. And for that, there was plenty of rat poison to be bought. And rat poison can kill a human as well – inadvertently, as a method for suicide, or as a murder weapon. It is kinda fun to see some of the same infrastructure issues, like garbage disposal and pest extermination in N.Y.City, addressed from different angles in different books – this one, On The Grid, as well as Rats, another fascinating science book that covers New York City engineering, infrastructure and politics of the time. All the threads tie in together….
Another topic addressed in each chapter was Prohibition. One can certainly die of a huge overdose of ethyl alcohol normally found in drinks, but at the time when producing and selling drinks was illegal, people still drank, perhaps even more. And what did they drink? Whatever they could find on the black market – home-made concoctions brewed by unsavory types more interested in profit than the safety of their product. Instead of ethyl, those drinks were mostly made of methyl (wood) alcohol which is much more dangerous in much smaller doses. Prohibition saw a large increase in drinking-related deaths, a fact often loudly pronounced by Norris, leading to the eventual end of Prohibition. Can we apply that thinking to the War On Drugs now?
And the story of Prohibition has another element to it – the importance of regulation. An unregulated substance is potentially dangerous. By solving a number of poisoning cases, and by doing their research on the toxicity of then easily available substances, Norris and Gettner have managed to initiate regulation of a number of toxins, or even their removal from the market altogether. Some substances that were found in everything, even touted as health potions (even radioactive substances!!!) were discovered by forensic toxicologists to be deadly, and were subsequently banned or rigorously controlled. Today we have entire federal agencies dealing with regulation of dangerous chemicals, but in the early 20th century, it was the time of laissez-faire murder, suicide, suffering and death.
Finally, after I finished this fascinating book, I realized it gave me something more: an anchor, or a scaffolding, or a context, for every story about poisons I see now. Now every blog post on Deborah’s blog makes more sense – I can fit it into a body of knowledge and understanding I would not have if I have not read the book. This really goes hand in hand with the recent discussions of #futureofcontext in journalism – see The Future Of Context for starters. The idea is that news stories do not provide enough context for readers who tune into a new topic for the first time. A story that is an update on an ongoing story is not comprehensible without some context, which the news story cannot provide. So now various media organizations are experimenting with ways to provide context for people who are just tuning in. The perfect source of context for a topic is a book, especially now that every book appears to have its own website with links and news and a blog and a Twitter feed and a Facebook page. The book provides context, and all these other things provide updates.
For example, reading Bonobo Handshake may not provide much more context for me about animal behavior and cognition since I already have that context, but it certainly now makes it easier for me to understand the news stories regarding conservation of great apes. And without that book I would never have sufficient background in the recent history of Congo to understand and appreciate this comment thread. ‘On The Grid’ gives me context for all news regarding infrastructure. Explaining Research is a great recent example of a book that is a great start on the topic, but which constantly reminds the reader that this field is in flux and that the book’s website contains frequent updates and additional resources. The Immortal Life of Henrietta Lacks provides fantastic context for the discussions of medical ethics and its evolution in the USA in the past several decades, which I riffed off a little bit in my latest interview.
What reading The Poisoner’s Handbook did for me is to give me enough knowledge and understanding on the topic that I can really appreciate it. I now get excited about news stories regarding poisons because I feel I understand them better. While reading Deborah Blum’s blog was interesting before, now it is more than interesting – it is exciting and I can’t wait for a new post to show up. I did not know how much I did not know. Now that I do, I want to know more. I am hungry for more knowledge, and more news, and more stories about toxins and poisons and how various strange and not so strange substances affect our bodies – where they come from, how they get in, how they hijack or disrupt our normal biochemical processes, how they kill us, and how do we figure that all out in the laboratory or in the basement of the mortuary. I hope you will feel the same once you finish reading this book. You will do that now, OK?

Seven Questions….with Yours Truly

Last week, my SciBling Jason Goldman interviewed me for his blog. The questions were not so much about blogging, journalism, Open Access and PLoS (except a little bit at the end) but more about science – how I got into it, what are my grad school experiences, what I think about doing research on animals, and such stuff. Jason posted the interview here, on his blog, on Friday, and he also let me repost it here on my blog as well, under the fold:

Continue reading

Are Zombies nocturnal?

day of the dead.jpgBlame ‘Night of the Living Dead’ for this, but many people mistakenly think that zombies are nocturnal, going around their business of walking around town with stilted gaits, looking for people whose brains they can eat, only at night.
You think you are safe during the day? You are dangerously wrong!
Zombies are on the prowl at all times of day and night! They are not nocturnal, they are arrhythmic! And insomniac. They never sleep!
Remember how one becomes a zombie in the first place? Through death, or Intercision, or, since this is a science blog and we need to explain this scientifically, through the effects of tetrodotoxin. In any case, the process incurs some permanent brain damage.
One of the brain centers that is thus permanently damaged is the circadian clock. But importantly, it is not just not ticking any more, it is in a permanent “day” state. What does that mean practically?
When the clock is in its “day” phase, it is very difficult to fall asleep. Thus insomnia.
When the clock is in its “day” phase, metabolism is high (higher than at night), thus zombies require a lot of energy all the time and quickly burn through all of it. Thus constant hunger for high-calory foods, like brains.
Insomnia, in turn, affects some hormones, like ghrelin and leptin, which control appetite. If you have a sleepless night or chronic insomnia, you also tend to eat more at night.
But at night the digestive function is high. As zombies’ clock is in the day state, their digestion is not as efficient. They have huge appetite, they eat a lot, but they do not digest it well, and what they digest they immediately burn. Which explains why they tend not to get fat, while living humans with insomnia do.
Finally, they have problems with wounds, you may have noticed. Healing of wounds requires growth hormone. But growth hormone is secreted only during sleep (actually, during slow sleep phases) and is likewise affected by ghrelin.
In short, a lot of the zombies’ physiology and behavior can be traced back to their loss of circadian function and having their clock being in a permanent “day” state.
But the real take-home message of this is…. don’t let your guard down during the day!
sbzombies_blogaroundtheclock.png
Picture of me as a Zombie (as well as of all my Sciblings – go around the blogs today to see them) drawn by Joseph Hewitt of Ataraxia Theatre whose latest project, GearHead RPG, is a sci-fi rogue-like game with giant robots and a random story generator – check it out.

Evolutionary Medicine: Does reindeer have a circadian stop-watch instead of a clock?

ResearchBlogging.orgWhenever I read a paper from Karl-Arne Stokkan’s lab, and I have read every one of them, no matter how dense the scientese language I always start imagining them running around the cold, dark Arctic, wielding enormous butterfly nets, looking for and catching reindeer (or ptarmigans, whichever animal the paper is about) to do their research.

Reindeer_bw.GIFlepidopterist.gif

If I was not so averse to cold, I’d think this would be the best career in science ever!
It is no surprise that their latest paper – A Circadian Clock Is Not Required in an Arctic Mammal (press release) – was widely covered by the media, both traditional and blogs, See, for example, The Scientist, BBC, Scientific American podcast and Wired Science.
Relevant, or just cool?
It is hard to find a science story that is more obviously in the “that’s cool” category, as opposed to the “that’s relevant” category. For the background on this debate, please read Ed Yong, David Dobbs, DeLene Beeland, Colin Schultz, and the series of Colin’s interviews with Carl Zimmer, Nicola Jones, David Dobbs, Jay Ingram, Ferris Jabr, Ed Yong and Ed Yong again.
I agree, it is a cool story. It is an attention-grabbing, nifty story about charismatic megafauna living in a strange wilderness. I first saw the work from the lab in a poster session at a conference many years ago, and of all the posters I saw that day, it is the reindeer one that I still remember after all these years.
Yet, the coolness of the story should not hide the fact that this research is also very relevant – both to the understanding of evolution and to human medicine. Let me try to explain what they did and why that is much more important than what a quick glance at the headlines may suggest. I did it only part-way a few years ago when I blogged about one of their earlier papers. But let me start with that earlier paper as background, for context.
Rhythms of Behavior
In their 2005 Nature paper (which was really just a tiny subset of a much longer, detailed paper they published elsewhere a couple of years later), Stokkan and colleagues used radiotelemetry to continuously monitor activity of reindeer – when they sleep and when they roam around foraging.
You should remember that up in the Arctic the summer is essentially one single day that lasts several months, while the winter is a continuous night that lasts several months. During these long periods of constant illumination, reindeer did not show rhythms in activity – they moved around and rested in bouts and bursts, at almost unpredictable times of “day”. Their circadian rhythms of behavior were gone.
But, during brief periods of spring and fall, during which there are 24-hour light-dark cycles of day and night, the reindeer (on the northern end of the mainland Norway, but not the population living even further north on Svaldbard which remained arrhythmic throughout), showed daily rhythms of activity, suggesting that this species may possess a circadian clock.
Rhythms of Physiology
In a couple of studies, including the latest one, the lab also looked into a physiological rhythm – that of melatonin synthesis and secretion by the pineal gland. Just as in activity rhythms, melatonin concentrations in the blood showed a daily (24-hour) rhythm only during the brief periods of spring and fall. Furthermore, in the latest paper, they kept three reindeer indoors for a couple of days, in light-tight stalls, and exposed them to 2.5-hour-long periods of darkness during the normal light phase of the day. Each such ‘dark pulse’ resulted in a sharp rise of blood melatonin, followed by just as abrupt elimination of melatonin as soon as the lights went back on.
reindeer melatonin.jpg
Rhythms of gene expression
Finally, in this latest paper, they also looked at the expression of two of the core clock genes in fibroblasts kept in vitro (in a dish). Fibroblasts are connective tissue cells found all around the body, probably taken out of reindeer by biopsy. In other mammals, e.g., in rodents, clock genes continue to cycle with a circadian period for a very long time in a dish. Yet, the reindeer fibroblasts, after a couple of very weak oscillations that were roughly in the circadian range, decayed into complete arrhytmicity – the cells were healthy, but their clocks were not ticking any more.
reindeer fibroblasts.jpg
What do these results suggest?
There is something fishy about the reindeer clock. It is not working the same way it does in other mammals studied to date. For example, seals and humans living in the Arctic have normal circadian rhythms of melatonin. Some other animals show daily rhythms in behavior. But in reindeer, rhythms in behavior and melatonin can be seen only if the environment is rhythmic as well. In constant light conditions, it appears that the clock is not working. But, is it? How do we know?
During the long winter night and the long summer day, the behavior of reindeer is not completely random. It is in bouts which show some regularity – these are ultradian rhythms with the period much shorter than 24 hours. If the clock is not working in reindeer, i.e., if there is no clock in this species, then the ultradian rhythms would persist during spring and fall as well. Yet we see circadian rhythms during these seasons – there is an underlying clock there which can be entrained to a 24-hour light-dark cycle.
This argues for the notion that the deer’s circadian clock, unless forced into synchrony by a 24 external cycle, undergoes something called frequency demultiplication. The idea is that the underlying cellular clock runs with a 24-hour period but that is sends signals downstream of the clock, triggering phenotypic (observable) events, several times during each cycle. The events happen always at the same phases of the cycle, and are usually happening every 12 or 8 or 6 or 4 or 3 or 2 or 1 hours – the divisors of 24. Likewise, the clock can trigger the event only every other cycle, resulting in a 48-hour period of the observable behavior.
If we forget for a moment the metaphor of the clock and think instead of a Player Piano, it is like the contraption plays the note G several times per cycle, always at the same moments during each cycle, but there is no need to limit each note to appear only once per cycle.
On the other hand, both the activity and melatonin rhythms appear to be driven directly by light and dark – like a stop-watch. In circadian parlance this is called an “hourglass clock” – an environmental trigger is needed to turn it over so it can start measuring time all over again. Dawn and dusk appear to directly stop and start the behavioral activity, and onset of dark stimulates while onset of light inhibits secretion of melatonin. An “hourglass clock” is an extreme example of a circadian clock with a very low amplitude.
While we mostly pay attention to period and phase, we should not forget that amplitude is important. Yes, amplitude is important. It determines how easy it is for the environmental cue to reset the clock to a new phase – lower the amplitude of the clock, easier it is to shift. In a very low-amplitude oscillator, onset of light (or dark) can instantly reset the clock to Phase Zero and start timing all over again – an “hourglass” behavior.
The molecular study of the reindeer fibroblasts also suggests a low-amplitude clock – there are a couple of weak oscillations to be seen before the rhythm goes away completely.
There may be other explanations for the observed data, e.g., masking (direct effect of light on behavior bypassing the clock) or relative coordination (weak and transient entrainment) but let’s not get too bogged down in arcane circadiana right now. For now, let’s say that the reindeer clock exists, that it is a very low-amplitude clock which entrains readily and immediately to light-dark cycles, while it fragments or demultiplies in long periods of constant conditions.
Why is this important to the reindeer?
During long night of the winter and the long day of the summer it does not make sense for the reindeer to behave in 24-hour cycles. Their internal drive to do so, driven by the clock, should be overpowered by the need to be flexible – in such a harsh environment, behavior needs to be opportunistic – if there’s a predator in sight: move away. If there is food in sight – go get it. If you are full and there is no danger, this is a good time to take a nap. One way to accomplish this is to de-couple the behavior from the clock. The other strategy is to have a clock that is very permissive to such opportunistic behavior – a very low-amplitude clock.
But why have clock at all?
Stokkan and colleagues stress that the day-night cycles in spring help reindeer time seasonal events, most importantly breeding. The calves/fawns should be born when the weather is the nicest and the food most plentiful. The reindeer use those few weeks of spring (and fall) to measure daylength (photoperiod) and thus time their seasonality – or in other words, to reset their internal calendar: the circannual clock.
But, what does it all mean?
All of the above deals only with one of the two hypotheses for the adaptive function (and thus evolution) of the circadian clock. This is the External Synchronization hypothesis. This means that it is adaptive for an organism to be synchronized (in its biochemistry, physiology and behavior) with the external environment – to sleep when it is safe to do so, to eat at times when it will be undisturbed, etc. In the case of reindeer, since there are no daily cycles in the environment for the most of the year, there is no adaptive value in keeping a 24-hour rhythm in behavior, so none is observed. But since Arctic is highly seasonal, and since the circadian clock, through daylength measurement (photoperiodism) times seasonal events, the clock is retained as an adaptive structure.
This is not so new – such things have been observed in cave animals, as well as in social insects.
What the paper does not address is the other hypothesis – the Internal Synchronization hypothesis for the existence of the circadian clock – to synchronize internal events. So a target cell does not need to keep producing (and wasting energy) to produce a hormone receptor except at the time when the endocrine gland is secreting the hormone. It is a way for the body to temporally divide potentially conflicting physiological functions so those that need to coincide do so, and those that conflict with each other are separated in time – do not occur simultaneously. In this hypothesis, the clock is the Coordination Center of all the physiological processes. Even if there is no cycle in the environment to adapt to, the clock is a necessity and will be retained no matter what for this internal function, though the period now need not be close to 24 hours any more.
What can be done next?
Unfortunately, reindeer are not fruitflies or mice or rats. They are not endangered (as far as I know), but they are not easy to keep in the laboratory in large numbers in ideal, controlled conditions, for long periods of time.
Out in the field, one is limited as to what one can do. The only output of the clock that can be monitored long-term in the field is gross locomotor activity. Yet, while easiest to do, this is probably the least reliable indicator of the workings of the clock. Behavior is too flexible and malleable, too susceptible to “masking” by direct effects of the environment (e.g., weather, predators, etc,). And measurement of just gross locomotor activity does not tell us which specific behaviors the animals are engaged in.
It would be so nice if a bunch of reindeer could be brought into a lab and placed under controlled lighting conditions for a year at a time. One could, first, monitor several different specific behaviors. For example, if feeding, drinking and defecation are rhythmic, that would suggest that the entire digestive system is under circadian control: the stomach, liver, pancreas, intestine and all of their enzymes. Likewise with drinking and urination – they can be indirect indicators of the rhytmicity of the kidneys and the rest of the excretory system.
In a lab, one could also continuously monitor some physiological parameters with simple, non-invasive techniques. One could, for example monitor body temperature, blood pressure and heart-rate, much more reliable markers of circadian output. One could also take more frequent blood samples (these are large animals, they can take it) and measure a whole plethora of hormones along with melatonin, e.g., cortisol, thyroid hormones, progesterone, estrogen, testosterone, etc (also useful for measuring seasonal responses). One could measure metabolites in urine and feces and also gain some insight into rhythms of the internal biochemistry and physiology. All of that with no surgery and no discomfort to the animals.
Then one can place reindeer in constant darkness and see if all these rhythms persist or decay over time. Then one can make a PhaseResponse Curve and thus test the amplitude of the underlying oscillator (or do that with entrainment to T-cycles, if you have been clicking on links all along, you’ll know what I’m talking about). One can test their reproductive response to photoperiod this way as well.
Finally, fibroblasts are peripheral cells. One cannot expect the group to dissect suprachiasmatic nuclei out of reindeer to check the state of the master pacemaker itself. And in a case of such a damped circadian system, testing a peripheral clock may not be very informative. Better fibroblasts than nothing, but there are big caveats about using them.
Remember that the circadian system is distributed all around the body, with each cell containing a molecular clock, but only the pacemaker cells in the suprachiasmatic nucleus are acting as a network. In a circadian system like the one in reindeer, where the system is low-amplitude to begin with, it is almost expected that peripheral clocks taken out of the body and isolated in a dish will not be able to sustain rhythms for very long. Yet those same cells, while inside of the body, may be perfectly rhythmic as a part of the ensemble of all the body cells, each sending entraining signals to the others every day, thus the entire system as a whole working quite well as a body-wide circadian clock. This can be monitored in real-time in transgenic mice, but the technology to do that in reindeer is still some years away.
Finally, one could test a hypothesis that the reindeer clock undergoes seasonal changes in its organization at the molecular level by comparing the performance of fibroblasts (and perhaps some other peripheral cells) taken out of animals at different times of year.
What’s up with this being medically relevant?
But why is all this important? Why is work on mice not sufficient and one needs to pay attention to a strange laboratory animal model like reindeer?
First, unlike rodents, reindeer is a large, mostly diurnal animal. Just like us.
a1 reindeer.jpg
Second, reindeer normally live in conditions that make people sick, yet they remain just fine, thank you. How do they do that?
Even humans who don’t live above the Arctic Circle (or in the Antarctica), tend to live in a 24-hour society with both light and social cues messing up with our internal rhythms.
We have complex circadian systems that are easy to get out of whack. We work night-shifts and rotating shifts and fly around the globe getting jet-lagged. Jet-lag is not desynchronization between the clock and the environment, it is internal desynchronization between all the cellular clocks in our bodies.
In the state of almost permanent jet-lag that many of us live in, a lot of things go wrong. We get sleeping disorders, eating disorders, obesity, compromised immunity leading to cancer, problems with reproduction, increase in psychiatric problems, the Seasonal Affective Disorder, prevalence of stomach ulcers and breast cancer in night-shift nurses, etc.
Why do we get all that and reindeer don’t? What is the trick they evolved to stay healthy in conditions that drive us insane and sick? Can we learn their trick, adopt it for our own medical practice, and use it? Those are kinds of things that a mouse and a rat cannot provide answers to, but reindeer can. I can’t think of another animal species that can do that for us. Which is why I am glad that Stokkan and friends are chasing reindeer with enormous butterfly nets across Arctic wasteland in the darkness of winter 😉
Lu, W., Meng, Q., Tyler, N., Stokkan, K., & Loudon, A. (2010). A Circadian Clock Is Not Required in an Arctic Mammal Current Biology, 20 (6), 533-537 DOI: 10.1016/j.cub.2010.01.042

Science Cafe Raleigh – Our bodies: the Final Frontier

From the NC Museum of Natural Sciences:

OUR BODIES: The Final Frontier
Tuesday, March 23, 2010 – 6:30-8:30 pm with discussion beginning
at 7:00 followed by Q&A
Location: Tir Na Nog 218 South Blount Street, Raleigh, 833-7795
We have come to think of the world as known. It isn’t. Even basic parts of our own bodies remain totally unexplored. For example, have you ever stopped to wonder why you are naked? Aside from naked mole rats, we are among the only land mammals to be essentially devoid of hair. Why? Join us for a discussion about the human body and its adaptations to a world filled with predators, pathogens and parasites. Bring your appendix, if you still have one, and learn about its special purpose.
About the Speaker:
Rob Dunn is an ecologist in the Department of Biology at North Carolina State University where he studies the global distribution of life and how it is changing as we change the world. He also studies ants. Dunn’s award-winning book “Every Living Thing” (Harper Collins, 2009) explores the strange limits of the living world and the stranger scientists that study them. His next book, “Clean Living is Bad for You … and Other Modern Consequences of Having Evolved in the Wild,” will be out in 2010. Dunn also writes articles for magazines including National Geographic, Natural History, Seed, Scientific American and National Wildlife. To read more of Rob’s writing, sign up for his email list at:
http://groups.google.com/group/Smallthingsconsidered.
RSVP to katey.ahmann@ncmail.net. For more information, contact Katey Ahmann at 919-733-7450, ext. 531.

My latest scientific paper: Extended Laying Interval of Ultimate Eggs of the Eastern Bluebird

ResearchBlogging.orgYes, years after I left the lab, I published a scientific paper. How did that happen?
Back in 2000, I published a paper on the way circadian clock controls the time of day when the eggs are laid in Japanese quail. Several years later, I wrote a blog post about that paper, trying to explain in lay terms what I did, why I did it, what I found, and how it fits into the broader context of this line of research. The paper was a physiology paper, and my blog post also focused on the physiological aspects of it.
But then, I wrote (back in March 2006 – eons ago in Web-time) an additional blog post on one of my old blogs (reposted on this one here, here and here) in which I followed further, thinking about the data in more ecological and evolutionary terms, and proposing hypotheses following from the data that can only be tested in other species out in the wild. As you can see if you click on the links, this post did not receive much commentary.
Then, about a year ago, I received an e-mail out of the blue, from a researcher at the Cornell Ornithology Lab, essentially offering to test one of the hypotheses I outlined in that post. My first reaction was “sure, go ahead, I am happy someone wants to do this, but please cite the blog post as the origin of the hypothesis”… The response was along the lines of “no, no, no – we are thinking about working WITH you on testing this hypothesis”. Wow! Sure, of course, I’m game!
They already had preliminary data which they sent to me to take a look. They are coming from an ecological tradition and are very familiar with the ecological literature, some of which they sent to me to read. On the other hand, I am coming from a physiological tradition and am very familiar with that literature, some of which I sent to them to read.
A month or so later, one of them, Caren Cooper, came down to Chapel Hill. We met and, over coffee, spent a couple of hours staring at the data and discussed what it all means. Then we got started at writing the paper.
And now, the paper is out: Caren B. Cooper, Margaret A. Voss, and Bora Zivkovic, Extended Laying Interval of Ultimate Eggs of the Eastern Bluebird, The Condor Nov 2009: Vol. 111, Issue 4, pg(s) 752-755 doi: 10.1525/cond.2009.090061
In this paper – which is really a preliminary pilot study (who knows, we may yet get a grant to do more) – Caren and Margaret set up video cameras on a bunch of nests of Eastern Bluebirds (Sialia sialis). From the tapes they got times when the eggs were laid. The times were approximate. But the analysis gave us exactly the same result when we used the times when the nest was obviously empty before the bird sat on it to lay the egg, the times when the bird first got up to reveal the egg to the camera, and the mid-point between those two times.
I am not aware of anyone ever looking at timing of egg-laying in wild birds out in the field. There is a huge literature on timing of laying in quail and chicken (and some in turkeys) in the laboratory, but none I am aware of in wild birds. Most researchers, when asked when their species lays eggs are surprised at the question and answer something along the lines of “no idea, but we find the eggs when we come to check the nests in the morning, so perhaps over night, or at dawn?” So, this paper is a first in this domain.
What we have shown is that bluebirds, just like chicken and quail, have an S-shaped pattern of egg-laying patterns (see my older post for theory and graphic visualization).
The question is: how does a bird “know” when to stop laying? When is enough enough? When is the clutch (all of the eggs laid in one breeding attempt) complete? Most of ecological literature is focused on energetics: are birds getting hungry, have they depleted some important source of energy, etc.
But the circadian field looks for internal mechanisms. Running a circadian clock takes very little energy. Even when the animals are extremely hungry, the clock keeps ticking with no changes in frequency (if anything, the amplitude gets bigger, implying even more work!). Even when an animal gets very sick and is dying, at the time when many bodily functions start ceasing, the clock works until the very end. Being produced by a molecular feedback loop in which some reactions use and others release energy, and all of this happening in just a small number of brain cells, the clock is very energy efficient and does not require the organism to be healthy and well fed.
What is important in regard to circadian regulation of egg-laying is to understand that female birds have not one, but two circadian clocks. Let’s call one of them A and the other one B. Clock A is located in the brain (or retinae or pineal or some combination, depending on the species) and is sensitive to light: it readily entrains to a light-dark cycle. No matter what the intrinsic frequency of the clock may be (as uncovered in constant darkness conditions), it is forced to a frequency of exactly 24 hours by the entraining power of the day/night cycle.
Clock B, on the other hand, is intimately tied to reproduction. It is a result of an interplay between the clock in the brain and neuro-endocrine signals between the brain and the ovary (which may itself house its own part of the clock). Brain clock sends hormonal signals to the ovary. Those signals entrain the ovarian rhythms AND result in ovulation. Ovulation itself produces hormones that signal to the brain clock and entrain it. This feedback loop is in itself The Clock. This clock is light-blind and its intrinsic frequency is not 24 hours – it is around 26-27 hours in both quail and chicken, and almost two days long in turkeys.
These two clocks, A and B, interact with each other. Let’s imagine a hypothetical scenario in which clocks A and B are very tightly coupled. The external light-dark cycles that all the birds in the wild are constantly exposed to entrain the clock A to the exactly 24 hours period. Clock B, being tightly coupled to Clock A is then also forced to oscillate with a period of exactly 24 hours. What would that mean to the bird? She would be laying one egg per day, always at exactly the same time of day, every single day of her life: in spring, summer, fall and winter. She’d spend all her resources on making big yolky eggs every day. She would be sitting on a huge pile of eggs throughout her life. She would not be able even to move short-distance to a better nesting ground, let alone prepare and undergo a long-distance migration. Her eggs would be also hatching at the rate of one per day. Thus, she would have progeny of a variety of ages at all times, each age having different requirements for care or abilities to follow the mother around. Some hatchlings would freeze to death in winter, or starve to death at time when the food is scarce. Others would die from predation at times when they are highly visible (in the snow) or just because there are so many of them they cannot all hide under a bush.
An opposite scenario: clocks A and B do not interact with each other at all. In this case, A would be entrained to the 24 hour cycle of night and day. Clock B, being light-blind, would freerun with its own endogenous frequency, i.e., with a period of roughly 26-27 hours. Again, the poor bird would be laying one egg per day all of her life. The only difference is that the eggs would not be laid always at the same time of day, but scattered all over the 24-hour cycle. Both scenarios are obviously maladaptive to the bird.
But, oscillator theory provides a third scenario in which clocks A and B are only loosely coupled. There are phase-relationships between the two clocks when they are coupled: A entrains B. There are phase-relationships when the two are at odds: A inhibits B (and thus no ovulation happens). The phase-relationships are dependent on daylength: when the days are short in winter A inhibits B and no eggs are laid. When the days are very long in the middle of the summer (or in constant light) all phases are permissive to ovulation and the clock B can freerun with its own period of 26-27 hours.
But the interesting phenomenon happens in-between, once the length of the day gets just a little bit longer in spring, in normal breeding season. There is only a narrow zone of phase-relationships in which the two clocks are coupled – outside of that zone, ovulation is inhibited. Thus the clock A starts ticking at the beginning of that zone (e.g., at dawn in some species, at around noon in quail) and starts freerunning through it until it “phase-locks” with the clock A and, for a while, appears to be running with the period of 24 hours. But underneath, the pulses of hormones are gradually shifting later and later, just a little bit each day. Finally, these hormonal influences allow the clock B to again break free from the clock A, freerun some more until it gets out of the permissive phase – the feedback loop is broken and the ovulations stops. The clutch is over.
a3%20OVI%20-%20medium%20PP.jpg
The resulting pattern is S-shaped: early in the clutch eggs are laid a little bit later each day, the middle of the clutch appears entrained to the 24-hour cycle, and the last egg or two again are laid later until the egg-laying stops completely. In quail, which was bred for centuries for egg-production, the selection affected the strength of coupling between the two clocks. Thus, in photoperiods (daylengths) that are just barely longer than the ‘critical photoperiod’ (the minimal daylength needed to provide any permissive phases at all, thus the first daylength in spring at which the bird can start laying), quail will have S-shaped patterns but the middle portion, the “straight one” that is entrained, is artificially long – I have seen clutches lasting for two months and consisting of 60 eggs!
Birds out in the wild, where natural selection is likely to produce an optimal clutch-size (not a maximal one that humans prefer), may or may not use the same mechanism to determine how and when the clutch starts and ends. So, what we did was see if Bluebirds also show the S-shaped pattern that would suggest they do. And they do:
Condor image.JPG
The first egg in the clutch is laid earlier than the subsequent eggs. All the eggs in the middle (1-6 of them, not 30 – we collapsed them all into one “time-point” in the graph) are laid at about the same time, indicating entrainment of B by A (i.e., to the light-dark cycle). The second-to-last egg may be laid a little later, and the very last egg is laid much later. These results suggest that quail is not a weird unique animal, or that Galliformes (chicken-like birds) are different from other kinds, e.g.., Passeriformes (songbirds). The mechanism is likely the same – not dependent on external factors like food and energy, but a result of a fine-honed system of interactions between two circadian clocks.
Of course, this is just a first observational study, but the results are encouraging. Next steps would be to: a) improve the temporal precision of measurements by, perhaps, installing thermo-couples in the nests (there is a huge but short-lasting body temperature spike exactly at the time of lay), b) increase the sample size, c) compare the bluebirds living in three very different latitudes where both the weather conditions and photoperiodic changes are different to see how the natural selection shaped their responses, and d) do a comparative study of a few more species belonging to other groups. We’ll see if we’ll try to submit a grant proposal in the future.
Unfortunately, this paper is not Open Access. I wanted to send it to PLoS ONE, which I think is the best journal in the world and IS the future of publishing. But it was important for Caren and Margaret to publish in a journal that their peers consider important, and Condor is a fine little journal for this. So I agreed to go along with it.
Also, the listing of the original blog post in the List Of References, to my dismay, disappeared between the Provisional PDF and Final PDF versions. It is now linked to inline in the text, placing it down to the level of the dreaded “personal communication”, once again foiling our attempts to give serious science blogging some respect. Ah well….
Interestingly, I did not know when the paper came out. Apparently, it was published back in November. I learned about it a couple of days ago when I got a first reprint request from a researcher in Russia!
But hey, I am happy. I got a paper published. And now I am using my blog and social networks to promote it… 😉
Cooper, C., Voss, M., & Zivkovic, B. (2009). Extended Laying Interval of Ultimate Eggs of the Eastern Bluebird The Condor, 111 (4), 752-755 DOI: 10.1525/cond.2009.090061