Friday, June 09, 2006

This blog has (finally) gone to SEED

So, the day has finally arrived - the Big Move to SEED scienceblogs. Go check out the brand new front page and all the old and new bloggers there.

My new blog, a fusion of all three of my blogs, will be a new brand, with a new name - A Blog Around The Clock, reflecting my age and musical taste, my usual blogging frequency and the area of my scientific expertise, all in one title.

The Banner was designed by Carel Pieter Brest Van Kempen who also runs a delightful science/art blog Rigor Vitae.

The new URL is, the new Atom feed is and the new RSS feed is

Please change your bookmarks, blogrolls and newsfeeds to reflect this move.

As I said before, Circadiana and The Magic School Bus will be closed (but not deleted), while Science And Politics will slow down and will re-focus on local North Carolina topics, including local politics (which includes following the career of John Edwards), and perhaps an occasional post for my readers from the Balkans. If you are still interested in those topics, you are welcome to retain the bookmarks, blogrolls and newsfeeds for Science And Politics as well, but I will not be insulted if you do not, as my main blogging effort will be over there, on my new SB blog.

I encourage you to go and check all 24 newbies over on SEED - all wonderful bloggers you should read if you are interested in science. Let me introduce my new fraternity-mates to you:

Carl Zimmer, the NYTimes science/evolution reporter, is moving The Loom from here to here.

Matt Nisbett, an expert on political communication and writer of a monthly column for the Skeptical Inquirer Online is moving his blog Framing-Science from here to here.

My fellow North Carolinian, medblogger Abel PharmBoy, is moving Terra Sigillata from here to here.

James Hrynyshyn, another fellow North Carolinian, is moving Island Of Doubt from here to here.

My favourite cognitive psychology blogger Chris is moving Mixing Memory from here to here.

Philosopher of biology John Wilkins is moving Evolving Thoughts from here to here.

Mike The Mad Biologist is moving from here to here.

I thought that one of my favourite science bloggers George Wilkinson has quit blogging, but no, he is also moving Keat's Telescope from here to here.

Reveres, experts on Avian Flu, are moving Effect Measure from here to here.

Karmen is moving her beautiful Chaotic Utopia from here to here.

Sandra Porter is moving Discovering Biology In A Digital World from here to here.

Nick Anthis is moving The Scientific Activist from here to here.

Joseph is moving Corpus Callosum from here to here.

Jake Young, another one of several neuroscientists joining the team, is moving Pure Pedantry from here to here.

Shelley Batts, another neuroscientist, is moving Retrospectacle from here to here.

Evil Monkey is moving Neurotopia from here to here.

Mike Dunford is moving The Questionable Authority from here to here.

Mark Chu-Carroll is moving Good Math, Bad Math from here to here.

David Ng and Benjamin Cohen are moving from Science Creative Quarterly and Annals of Science to World's Fair.

The Cheerful Oncologist is moving from here to here.

Dr.Charles is moving the eponimous Examining Room from here to here.

Dr. X is moving Chemblog from here to here.

The rowdy bonobos from Dr. Joan Bushwell's Chimpanzee Refuge are moving from here to here.

Steinn, an astrophysicist, is moving Dynamics Of Cats from here to here.

Finally, Jonah Lerer is a SEED staffer, starting his own blog called The Frontal Cortex.

There were few surprises for me on this list. Two good blogfriends of mine (Revere and Mike the Mad Biologist) managed to keep me in the dark about their move until two days ago. On the other hand, two bloggers I thought were going to accept the invitation, are not on the list (yet?). Almost all of the others I knew about.

The SEED overlords intend to add more bloggers before the end of the year so keep an eye on SEED - that is where the SciBlogging action is going to be.

Thursday, June 08, 2006

Jet-lagged sports teams

Study says West coast teams have advantage:
Ingmundson, who is also a a diplomate with the American Board of Sleep Medicine, says western-based teams may have an advantage in sporting events in which cross-country road trips are invloved. He has found that a disruption in eastern teams` circadian rhythms – or internal clocks – may contribute directly to poor performances like Miami`s versus Dallas.

"The mechanism is relatively straightforward, at least superficially," explains Ingmundson. "Performance on many cognitive and motor tasks peaks in late afternoon. Teams travelling west to east to play night games are playing with their biological clocks set earlier, close to the most favorable time, and teams traveling from east to west are playing at relatively later point in their biological "day," conferring a relative handicap."
Read the rest...

Tuesday, June 06, 2006

Sleep News

Benefits of Power Napping


New research explores why we're sleepy after we eat


Serotonin, Acting In A Specific Brain Region, Promotes Sleep In Fruit Flies:
Researchers have found that the neurotransmitter serotonin, known to affect many behaviors, also appears to promote lasting, quality sleep in an animal model for understanding how sleep is regulated. While central to the lives of most animals, the proper regulation sleep remains a largely enigmatic process.
(The actual paper is here: A Sleep-Promoting Role for the Drosophila Serotonin Receptor 1A)

Friday, June 02, 2006

Take your iPod to bed

Interesting idea, via Sleep Disorders blog: a pre-recorded morning talk-show puts you to sleep because it is a distraction from Real Life worries that may otherwise keep you awake at night, yet no need to worry that you'll miss something interesting.

I need to try me some Diane Rehm show. With her slow, monotonous manner of talking, I bet she would put me to sleep in five seconds. It almost puts me to sleep while I'm driving!

Wednesday, May 31, 2006

Early Bird Gets The Worm....or Seed

(Image stolen from Xtinpore)

Well, I may not be the earliest bird, certainly not early enough to grab the worm, but I am early enough in the game to be able to get some seed, or more precisely SEED.

Yup, starting this Friday, this blog will fuse with my other two blogs (Science And Politics and The Magic School Bus) and move to the ever-growing

It does not work right now, but on Friday you will be able to access the new blog at this URL.

I'll give you the Feed once I get it, so you can all change your bookmarks, blogrolls and newsfeeds to the new address.

The complete archives of this blog will remain here as there are many incoming links, but I will slowly, over the next few months, republish some of the best Circadiana posts over there. I hope you all move there with me - the new blog will be even better (and prettier) than this one.

Update: Due to technical problems, the new blogs will nost start tomorrow (Friday) but later, hopefully Monday of next week. I'll keep you posted.

Wednesday, May 24, 2006

Eight Hours a Circadian Rhythm Do Not Make

There is a new study on PLoS - Biology that is getting some traction in the media and which caught my attention because it was supposed to be about circadian rhythms. So, I downloaded the paper and read it through to see what it is really about.

Well, it is a decent study, but, unfortunately, it has nothing to do with circadian rhythms. Many examples of tritrophic relationships involve parasitoids (usually small wasps) being attracted by plant volatiles which are released in response to herbivory by insect (usually moth) larvae. So, if a caterpillar munches on a plant, that plant releases chemicals which attract the wasps. When a wasp arrives, she injects her eggs into the caterpillar, often together with a cocktail of toxins or other chemicals that alter the development of the caterpillar, keeping it in the larval stage longer than normal, thus giving wasp eggs sufficient time to hatch and the little wasp larvae to eat their way out (and in the process devouring and killing the caterpillar).

It has also been known for a while now that wasps are strictly diurnal, i.e., they fly only during the day. It has also been known for a couple of years now that plants release the alarm chemicals mostly during the day. Production of this odors takes energy which would be wasted at night when the wasps are not active.

Activity of caterpillars is much harder to assess, and many people in the field swear that there is no diurnal rhythm of their activity, i.e., they are as likely to feed on leaves at night as during the day, though some mild rhtyhms were found in some species.

What this paper addresses is the problem with the previous studies of the caterpillar rhythms. Those were assessed on larvae placed on their host plants. Thus, those were not well-controlled experiments because apart from a light-dark cycle, the larvae were simultaneously exposed to signals generated by the plants.

So, in this paper, the larve were kept in cups and fed synthetic food. They were assayed in light and in darkness in a series of experiments, first in the absence of plants, then in the presence of uninjured plants, and finally in the presence of day-time and night-time volatiles released by either uninjured or insect-injured plants.

Result: the activity of caterpillars was affected by the presence of plants.

Larvae were more likely to hide in the presence of plants than in their absence, even more in the presence of day-time emissions than night-time emission from uninjured plants, and even more in the presence of day-time emissions from the injured plants, suggesting that plant volatiles, especially those produced during the day, and especially those produced by grazed plants, inhibit foraging activity of larvae and promote hiding activity of larvae. The statistics are nice and strong and the conclusion drawn from the data is correct.

If they framed it in this way, the study would be fine. But, for some unkown reason, they decided to frame the study within the context of "sexier" circadian research.
"Although many organisms show daily rhythms in their activity patterns, the mechanistic causes of these patterns are poorly understood."
is the first sentence of the Abstract of the paper that contains the statement even in the title: Plant Volatiles, Rather than Light, Determine the Nocturnal Behavior of a Caterpillar (PDF).

Their first reference is to the Saunders' book on Insect Clocks and most of the Introduction and Discussion treats the results of the paper in the circadian context.
"The caterpillars are believed to have evolved a nocturnal lifestyle in order to avoid predatory wasps that maraud throughout the day, but why they don't use light cues like most other organisms remains a mystery, Takabayashi says" in a press release.
Yet, their experimental methods cannot say anything about response of circadian rhythms to light in these caterpillars. Why?

First, there is nothing said about the pre-treatment. Were the insects kept in light-dark cycle, constant dark or constant light prior to the onset of the experiment? Were they kept on plants or on artifical diet prior to the onset of the experiment? This information is essential to evaluate how entrained their circadian rhythms were prior to the experiment.

Was the onset of the experiment at the lights-off, lights-on or some other phase of the pre-treatment cycle? Just swithing on or off the lights on them at just any time of day or night will not shift their clocks so fast, or even at all, depending on their phase response.

Even if they have a fast-resetting Type O Phase Response Curve (and there is no reason to believe they do - those are rare in the animal kingdom), monitoring the response for just eight hours is not enough - the clocks take much longer to reset.

There is a reason why circadian rhythms are monitored over many days, weeks, months or even years and why the data collected over the first 2-5 days after any kind of treatment (light transition, light pulse, injections of chemicals, etc.) are not used in statistical analysis - the researcher waits that long until the post-treatment rhythm stabilizes.

So, from their data, we cannot say if plant volatiles affect the circadian clock. We also cannot say if the caterpillar clock is or is not responsive to light. The data are consistent with the hypothesis that their clock is light-blind, but is equally consistent with the hypothesis that it is not. The data are consistent with the hypothesis that plant volatiles entrain the clock, but also consistent with the hypothesis that plant odors exert only a masking effect on the overt rhythm of activity - the hands of the clock - without affecting the underlying gears of the clock.

Carl Zimmer wisely avoids any discussion of circadian clocks in his excellent description of what the paper really shows on Loom. The behavior is affected by plant volatiles. Period. Excellent demonstration of the effect. No need to bring in the stuff that was not really addressed by the research, no matter how much the authors wish it may be so.

Most of the others just parrot the press release, e.g., Biology News, Brightsurf, Our Diagnosis, New Scientist, 3 Quarks daily, EurekAlert and Biology Blog.

Tangled Bank

Tangled Bank #54 is up on Science And Politics

Tuesday, May 23, 2006

Clock in the primate adrenal

From Afarensis, I got a new paper about circadian rhythms in primates: Twenty-four hour rhythmic gene expression in the rhesus macaque adrenal gland (PDF), by Dario Lemos, Jodi Downs and Henryk Urbanski.

The way the study is presented in the press release (now offline!), it sounds like this is a big surprising breakthrough, but I am not too impressed. The work is good and useful, but the findings are far from Earth-shattering.

Using microarrays, they have shown that expression of many genes cycle in a circadian manner in the adrenal glands of monkeys. The work is in vivo, and we have known for more than ten years that every cell in the body contains a clock and that clock genes cycle in every cell in our body. There was even a curious old study showing that there is a rhythm in red blood cells - no nucleus there!

Also, people have done time-series analysis of gene expression in various tissues using microarrays, and in each tissue those genes that code for proteins that are essential for that tissue's function show a circadian profile of expression (while the housekeeping genes do not). So, genes for liver enzymes cycle in the liver, genes that code for proteins involved in muscle contraction show circadian patterns of expression in muscle cells, etc. Genes that are not involved in that organ's main function are either expressed constituitively (at a constant level) or not expressed at all.

If you take any tissue out of the body and culture it, the rhythms persist, at least for several days, showing that all cells in our body are competent clocks, not just driven into rhythmicity by a daily signal from the SCN. This has been done with a number of tissues to date, including heart, lung, liver and fibroblasts.

I'd get really excited if, in their next study, they transplant an adrenal from one monkey to another and force all rhythms of the (SCN-lesioned) host to adopt the period and phase of the transplant - that would show that the adrenal is not just a clock (which is boring - every cell is a clock), but a pacemaker of the circadian system.

People in the field of chronobiology have targeted the adrenal as a potential pacemaker for a long time (since 1948 work by Curt Richter) and many experiments have been performed in the past in rodents and chickens (a friend of mine did his PhD dissertation on this topic) and all the results were always negative - adrenal is functioning as a peripheral clock, but not a pacemaker.

Sunday, May 21, 2006

Tangled Bank - last call for submissions

The Tangled Bank

The next edition of Tangled Bank is fast approaching - it will appear on my other blog Science And Politics on Wednesday May 24th, very early in the morning. The deadline is 23rd at 8pm ET.

I have only eight entries so far - come on, people! Out of more than 400 science-related blogs, I get only eight posts?

Some carnivals have very strict entry policies - Carnival of Liberals is limited to the 10 best posts, and I And The Bird is limited to one post per blogger. Some carnivals actively encourage multiple submissions from each blogger, e.g., Teaching Carnival, Circus of the Spineless and Animalcules. Most other carnivals are ambiguous about the rules and it is up to each host to spell those out.

I am one of those hosts who likes big carnivals and encourages multiple entries. So, for this Tangled Bank send your best. If you send 15 entries, I'll pick 2 or 3 I like the best, but do not be afraid to send in multiple suggestions. Also, you can nominate someone else's post if you think it is really good and deserves a broader audience.

Send your entries to: Coturnix1 AT aol DOT com

Wednesday, May 17, 2006

Project Exploration

You may have noticed a new button on my sidebar that looks like this:
Project Exploration

If you click on it, you will be transported to the homepage of one of my favourite science educational programs - the Project Exploration. This project is the brainchild of paleontologist Paul Sereno and his wife, historian and educator Gabrielle Lyons.

If you do not know who Paul Sereno is, you are probably not interested in dinosaurs at all, as he is the #1 Big Star of Dinosaur Paleontology. Among else, he has discovered Carcharodontosaurus saharicus, one of the largest dinosaur carnivores - the African version of T.rex. Jobaria tiguidensis is the best preserved skeleton of a long-necked dinosaur. Sarcosuchus imperator, better known as Supercroc was big enough crocodile to hunt and eat dinosaurs. He has also discovered Eoraptor lunensis and Herrerasaurus ischigualastensis, two of the oldest dino fossils belonging to some of the earliest dinosaurs. Deltadromeus agilis, discovered by Gabrielle Lyons, was one of the fastest dinosaurs ever.

I had a good fortune to see Sereno give a talk and briefly to introduce myself to him, at the 2000 meeting of the Society for Integrative and Comparative Biology in Chicago. My brother knows him much better, as he and Gabrielle knew each other from grad school. Thanks to their friendship I got, over the years, a bunch of informational materials from the Project Exploration, as well as some really cool stuff, like some Sahara sand, a small plant fossil and several T-shirts that you cannot buy - they are not for sale. One day when I get out of financial problems, I will make it an annual ritual to donate to their program, devoted to bringing excitement about science to inner-city schoolchildren, particularly minorities and girls. In the meantime, I hope that you donate. They do not take any money from the government and depend on individual donations for their operation. You can donate your money, or alternatives (stocks, time, work), easily through their website.

So, click on the button now, or whenever you want in the future, to see what they are doing, to get help if you are a science teacher, or to donate to a worthy cause.

Update: Tara reminds me that it may be important to show you their financial report, as well as the outcomes of their work:
Our programs are creating pipelines to future careers in science:

* Students participating in our field programs are graduating high school at an 18% higher rate than their peers.
* Students are pursuing science in college—25% of all students and 34% of our girls declare science as their major.
* The girls in our programs are pursuing science in college at five times the national average.

Clocks in Bacteria V: How about E.coli?

In the previous posts in this series, I covered the circadian clocks in Synechococcus, potential circadian clocks in a couple of other bacteria, and the presence of clock genes (thus potentially clocks) in a number of other bacteria. But what happened to the microbiological workhorse, the Escherichia coli? Does it have a clock? Hasn't anyone checked?

Believe it or not, this question is colored by politics. But I have to give you a little background first. Latter half of the 19th and the first half of the 20th century saw a number of researchers discovering circadian rhythms independently from each other. They came from different backgrounds and did research in a variety of questions in different organisms. There were botanists and entomologists, physiologists and ecologists, behavioral biologists and microbiologists, evolutionary biologists and physicians.

The founding moment of the field was the Cold Spring Harbour meeting in 1960, which produced the Proceedings (Cold Spring Harbor Symposia on Quantitative Biology: Volume XXV. Biological Clocks. New York: Cold Spring Harbor Press, 1960.) which is, arguably, the founding document of the field. It is there and then that everyone realized that they were all studying the same phenomenon, they agreed on common terminology, and learned from each other what became standard experimantal methods in the field.

Not much later, in the 1970s, the Society for Research in Biological Rhythms (SRBR) was formed and had its first meeting. Apart from wonderful talks and posters, and rambunctious partying, one of the key moments of the meeting was the election of the Society President. By that time, something akin to War of the Roses was going on in the field. The two candidates for the position were the leaders of the two factions.

One faction, led by Franz Halberg (who coined the term "circadian" among else), was medically minded and argued for a practical, applied approach to the study of rhythmic phenomena, coupling mathematical modelling with clinical studies in humans and some model animals like rats and mice. The other faction, led by Colin Pittendrigh (student of Theodozius Dobzhansky), came from an evolutionary, ecological and ethological tradition, arguing for an integrative and comparative approach to the study of the basic science of biological rhythms.

Fortunately for all, Pittendrigh won. The rest is history - chronobiology took off and nobody could stop its meteoric rise. The human/medical approach that plagued the sleep research for so many decades was avoided by chronobiology. But the bad blood between Pittendrighians and the Halbergians remained for a long time - it actually still simmers underneath the surface, especially among the seniors in the field. Most of the top researchers in the field, the meeting organizers, the Society officials, textbook writers, journal editors, and the plenary lecture speakers are Pittendrigh's academic children, grandchildren and great-grandchildren (OK, I am one, too).

When I mentioned, in the first post in this series, that it was believed for decades that bacteria had no clocks, I was just parroting the party line. But there were some people who thought otherwise all along. Here is what Franz Halberg himself says about the question of clocks in Echerichia coli:

A circadian rhythm in bacteria was documented time-microscopically in 1961 on impeccable data collected by Lore A. Rogers (a noted bacteriologist described by a Cosmos Club Vignette of December 1967 as "the bright star in the [U.S. Department of Agriculture's] scientific horizon before World War II"). Rogers' data stemmed from a fluid culture of E. coli, analyzed both by a periodogram and by power spectra, showing clear free-running circadians. Nonetheless, for years international symposia and cell chronobiologists in particular, including a committee formed by them in 1975, held the view that circadians are a property only of eukaryotes. I wrote to each committee member asking why they ignored the demonstration in E. coli and the extension of the finding by Sturtevant in John Pauly's laboratory in Arkansas. I regarded, and continue to regard the organizers as friends. Both Woody Hastings and the late Hans-Georg Schweiger thereafter extended their focus to circaseptans, documenting their open mind. Schweiger became a visiting professor at the University of Minnesota and was my house guest (and I his house and institute guest), and in later years cooperated extremely closely. A friend on the committee, however, wrote that he "ate crow" and noted that the "consensus" had been that there were "too many analyses" in the 1961 publication and again too much time-microscopy in the follow-up study, a thesis notwithstanding. The consensus was also in keeping with negative unpublished results by several symposium participants; so went the critique leading to the committee's decree that circadians are limited to eukaryotes. Jürgen Aschoff also responded by asking something like "Do you wish to hold us responsible for posterity?" I answered in a qualified affirmative, that the rules we postulate today may be revised tomorrow, always based on data. Microbial circadians abound today and constitute an active field of investigation.[1]
Ah, how diplomatically he had to put it for publication!

Well, I dug through Google Scholar, then through ISI Web of Science, and none of the papers Halberg mentions (see below) exist online - they are just too old. So, I cannot tell you now what I think about this question. Perhaps one day I'll be idle and have a lot of time and will dig out and photocopy the hardcopies of these papers at the library and check the data myself. For now, let's keep the question open.

Perhaps the 1930 data were nice and clear, while 1970s data not so because of decades of relaxed selection for rhythmicity in laboratory cultures of E.coli held in acyclic conditions in the incubators. Perhaps they just lost rhythms during the intervening four decades. A new test should, perhaps, be performed on fresh wild-caught Escherichia coli.

At least we know that short-period cycles can evolve in E.coli under artifical selection [7], so, even if they do not naturally have circadian clocks, we can make them evolve one and solve the political problem once and for all.

[1] Franz Halberg et al. Transdisciplinary unifying implications of circadian findings in the 1950s. Journal of Circadian Rhythms 2003, 1:2

[2] Halberg F, Conner RL: Circadian organization and microbiology: Variance spectra and a periodogram on behavior of Escherichia coli growing in fluid culture. Proc minn Acad Sci 1961, 29:227-239.

[3] Rogers LA, Greenbank GR: The intermittent growth of bacterial cultures. J Bacteriol 1930, 19:181-190.

[4] Halberg F, Cornélissen G: The spectrum of rhythms in microorganisms revisited. Chronobiologia 1991, 18:114.

[5] Sturtevant R: Circadian patterns in linear growth of Escherichia coli. Anat Rec 1973, 175:453.

[6] Sturtevant R: Circadian variability in Klebsiella demonstrated by cosinor analysis. Int J Chronobiol 1973, 1:141-146.

[7] Michael B. Elowitz and Stanislas Leibler, A synthetic oscillatory network of transcriptional regulators. Nature 403, 335-338 (20 January 2000)

Previously in this series:
Circadian Clocks in Microorganisms
Clocks in Bacteria I: Synechococcus elongatus
Clocks in Bacteria II: Adaptive Function of Clocks in Cyanobacteria
Clocks in Bacteria III: Evolution of Clocks in Cyanobacteria
Clocks in Bacteria IV: Clocks in other bacteria

Sunday, May 14, 2006

Tangled Bank - call for submissions

The Tangled BankNext edition of Tangled Bank, the blog carnival covering science, nature, medicine, environment and the intersection between science and society, will be held on Wednesday, May 24th, on my other blog, Science And Politics. Send your entries by Tuesday, May 23th at 5pm (Eastern) to: Coturnix1 AT aol DOT com.

Monday, May 08, 2006

Cory Doctorow on Circadiana

Cory Doctorow gave an interview to recently and mentioned Circadiana there. Although I am thrilled that he likes this place, he made two mistakes:

First, I am not a she.

Second, Circadiana has not tapered off - it is more active than ever!

Friday, May 05, 2006

Ambien + Phenergan + Driving = A Big No-No

Seems like there is a good deal of interest today in Rep Patrick Kennedy's one-car accident last evening that he has attributed to taking a combination of the prescription sleep aid, Ambien (zolpidem tartrate), and Phenergan (promethazine), an old phenothiazine antipsychotic drug most often used now to treat nausea and gastrointestinal upset.
Then, Abel PharmBoy proceeds to explains how Ambien and Phenergan work and ends on this note:
However, this should be a lesson to all who take Ambien that they should 1) go immediately to bed after taking the drug, 2) do not combine it with any other CNS depressant, including OTC antihistamines or alcohol, and 3) certainly do not drive an automobile after taking such a drug combination.

Alcohol is not necessary to explain this case... unless one is trying to make a tabloid story out of this unfortunate incident.

Wednesday, May 03, 2006

Smoking (and Quitting) affects the Perception of Time

I wrote before about the effects of circadian time and/or body temperature on time perception. But, did you know that being a smoker and being placed in a situation in which lighting up is prohibited can also warp the sense of the passage of time? Here are a couple of papers on that topic:

First, an older, 2003, study, as reported here:

Time Perception Impaired When Smokers Stop:
In a recent study, 20 daily smokers, who went without a cigarette for 24 hours, overestimated the duration of a 45 second interval. To the abstaining smokers, the interval felt approximately 50 percent longer than 45 seconds or more than one minute.
In the study, 22 nonsmokers (12 male and 10 female), and 20 daily smokers (12 male and 8 female), ages 18 to 41, were asked to estimate the duration of a 45 second period of time in a laboratory setting. The smokers were asked to participate in two sessions, once while smoking as usual and once after having stopped for 24 hours.

During each session, the participants were given these instructions: "In a moment, I'm going to say 'start' and then I will say 'stop.' When I say 'stop,' please tell me how much time you think has gone by in seconds. Please try not to count, but just tell me how much time you feel has gone by. Do you have any questions? Ready? Start. [45 second elapse] Stop."

The time estimates made by the nonsmokers and the smokers before the abstinence period were similar and fairly accurate. However, after 24 hours without a cigarette, the smoker's accuracy declined significantly compared to both the nonsmokers and their own estimates before the abstinence period. There were no gender differences in any of the outcomes.

The researchers conclude, "That 24-hour cigarette smoking abstinence can alter perceptions of time in a healthy, young, non-clinical population of smokers emphasizes the need for future research to delineate the attention --altering effects of nicotine and nicotine withdrawal on addiction processes."
More recently, a 2005 paper on the same subject:

Sayette MA, Loewenstein G, Kirchner TR, Travis T., Effects of smoking urge on temporal cognition, Psychol Addict Behav. 2005 Mar;19(1):88-93.
The authors examined temporal aspects of smoking urge. In Experiment 1, smokers assigned to high- or low-urge conditions were informed they would be allowed to smoke in 2.5 min. They next completed measures of time perception. High-urge smokers reported 45 s to pass significantly more slowly than did low-urge smokers. In Experiment 2, the high-urge smokers from Experiment 1 anticipated that their urges would climb steadily over the next 45 min if they were not permitted to smoke. Another group of high-urge smokers actually reported their urges over 45 min. These urge ratings did not show the steady rise anticipated by the first group. Results suggest that smoking urge may affect time perception and that craving smokers overpredict the duration and intensity of their own future smoking urges if they abstain.
The latter paper is also analyzed and explained by Chris of Mixing Memory - you should go and read it here.

Sunday, April 30, 2006

Clocks in Bacteria IV: Clocks in other bacteria

For decades, it was thought that prokaryotes did not have circadian clocks. Then, a clock was discovered in a unicellular cyanobacterium, Synechococcus (later also in Synechocystis [1] and Trichodesmium [2]) which quickly became an important model in the study of circadian rhythms in general. Still, it was thought, for ten years or so, that no other prokaryotes had a circadian clock. Recently, the clock genes were found in filamentous (chain-forming) cyanobacteria, as well as a whole host of other bacteria and archaea. However, having clock genes does not neccessarily translate into having a functioning clock - the genes may have other functions (e.g., photoreception, or DNA repair) in bacteria other than Synechococcus.

So, two recent papers tried to address this question - do photosynthetic bacteria exhibit circadian rhythms? And the results of the two studies, in two different species of bacteria, have some interesting similarities to each other, so let's look at them in parallel.

Van Praag et al.[3], used Rhodospirillum rubrum, a gram-negative purple non-sulfur bacteria. Min et al.[4], also chose a purple photosynthetic bacterium Rhodobacter sphaeroides. In the former, the measured output was hydrogenase uptake, while in the latter a battery of luciferase reporter genes was inserted in the genome - strains exhibiting fluoresecence (presumably those in which the construct got inserted behind a promoter) were used in the study.

In the first study (click on images to enlarge), hydrogenase uptake was measured in unoxic (anaerobic) conditions in constant light (LL) at 32oC, and in constant darkness at 32oC and 16oC. In each of the three conditions, a rhythm was observed. The period of the freerunning rhythms was markedly different between the three conditions. In LL-32oC, period was ultradian: 12.1 hours. In DD at 32oC, the period was also ultradian: 14.8 hours. Only in DD at 16oC was the rhythm within a circadian range: 23.4 hours.

In the second study, light output was measured in three experiments. In all three, bacteria were assayed in constant darkness at 23oC. In the first and second groups, bacteria were pre-treated and their putative clocks entrained by a warm-cold-warm cycle prior to release into constant conditions. In the third group, the pre-treatments was exposure to a light-dark cycle prior to release into constant conditions. The first group was tested under aerobic conditions, while the second and the thir group were tested under anaerobic conditions.

Again, rhythms were observed in all three groups. What was observed was a difference in phase at which the rhythm begins dependent on the type of entraining cycle preceding the testing. The most important difference, however, was the difference in the freerunning period between the aerobic and anaerobic treatments. In the aerobic group, period was circadian: 20.5 hours. In the anaerobic conditions, the period was ultradian: 10.6 and 12.7 in groups II and III respectively.

What does this all mean? Temperature, light and oxygenation all appeared to have an effect on period. These experiments are difficult to do - if one was working with rodents or insects, the natural thing would be to test a large number of animals at several different temperatures to test for the possible lack of temperature compensation of the circadian rhythm, as well as at several different light intensities to test for the Aschoff's Rule. It is possible that this is a circadian clock that is not well temperature compensated, that is extremely sensitive to light, and that is based on the red-ox environment.

The way the studies have been reported, it is not clear that the rhythms are actually circadian, or if it just happened that some of the rhythms fell into the circadian range by accident. What is clear is that these bacteria generate endogenous rhythms. Are these rhythms circadian or not, and if so, are they driven by core-clock genes kaiA, kaiB and kaiC remains to be elucidated in the future.

[1] Aoki S, Kondo T, Wada H, and Ishiura M (1997) Circadian rhythm of the cyanobacterium Synechocystis sp. strain PCC 6803 in the dark. J Bacteriology 179:5751-5755.

[2] Chen YB, Domonic B, Mellon MT, and Zehr JP (1998) Circadian rhythm of nitrogenase gene expression in the diazotrophic filamentous nonheterocystous cyanobacterium Trichodesmium sp. strain IMS 101. J Bacteriology 180:3598-3605.

[3] Esther Van Praag, Robert Degli Agosti and Reinhard Bachofen, Rhythmic Activity of Uptake Hydrogenase in the Prokaryote Rhodospirillum rubrum, JOURNAL OF BIOLOGICAL RHYTHMS, Vol. 15 No. 3, June 2000 218-224

[4] Hongtao Min, Haitao Guo, Jin Xiong, Rhythmic gene expression in a purple photosynthetic bacterium, Rhodobacter sphaeroides, FEBS Letters 579 (2005) 808–812

Previously in this series:
Circadian Clocks in Microorganisms
Clocks in Bacteria I: Synechococcus elongatus
Clocks in Bacteria II: Adaptive Function of Clocks in Cyanobacteria
Clocks in Bacteria III: Evolution of Clocks in Cyanobacteria

Monday, April 24, 2006

Politics of Periodicity

How I wish I could see this seminar at The Johns Hopkins University:

Thurs., April 27, 4 p.m. "Circadian Oscillators in the Brain: Politics of Periodicity," a Biology seminar with Eric Herzog, Washington University; 100 Mudd. HW

Eric is a great speaker - I wonder what is he going to talk about! I am assuming that "politics" refers to the "negotiation" between different types of clock cells in the mammalian SCN, each with a different endogenous period, as to what period will the final output have. This will entail signalling mechanisms between cells, I assume, as well as phase-shifting properties of the cells.

Anyone there at John Hopkins who can go, watch and blog this?

Sunday, April 23, 2006

Drinking mothers - perpetually jet-lagged offspring

Prenatal alcohol exposure can alter circadian rhythms in offspring
Children with fetal alcohol spectrum disorders (FASD) suffer from a variety of behavioral alterations. For example, they may exhibit alterations in sleeping and eating patterns, which may indicate that their circadian systems which control biological rhythms have been affected by alcohol exposure during development. A rodent study in the May issue of Alcoholism: Clinical & Experimental Research confirms that alcohol exposure during a period equivalent to the third human trimester influences the ability to synchronize circadian rhythms to light cues.


For this study, researchers exposed male Sprague-Dawley rats to 6.0 g/kg of alcohol per day (n = 8), using an artificial rearing procedure, from postnatal days four through nine. The alcohol level represented heavy binge drinking. An artificially reared control group (n = 8) and a normally reared control group (n = 8) were also included in the study design. At 10 to 12 weeks of age, wheel-running behavior was continuously measured for eight days under a 12-hour light/12-hour dark (LD) cycle. Then the cycle was delayed by six hours and the rats were exposed to a new LD cycle for an additional six days. Their adjustment to the new cycle was evaluated.


"This is the equivalent to a person undergoing exposure to 'jet lag,'" noted Earnest. "Basically, if you take a human and go across a number of time zones from east to west, similar to the light/dark cycle of these animals, some people will shift quickly, and some will not, and may even experience some physical problems or illness because of effects on their immune system. The responses of the alcohol-treated animals indicated that they resynchronized to the shifted light/dark cycle more slowly than the control animals."

The implications of these results for humans, added Earnest, are much broader than the term "jet lag" might indicate. "These individuals are going to have difficulties, in terms of their ability to function, while traveling across time zones and also during shift work," he said. "There are a couple of prominent examples in history regarding this: the Exxon Valdez and Chernobyl. The captain of the Exxon Valdez was not only working shift work, but he was drinking too, and unable to maintain a normal, necessary performance. With Chernobyl, the shift-work schedules were inappropriate and, at the time that the accident happened, poor mental and physical performances contributed to the disaster."

The underlying message, said Thomas, is that drinking alcohol during pregnancy can have long-lasting damaging effects to the offspring. "There is currently no known safe amount of alcohol that can be consumed during pregnancy, so it is best to abstain from alcohol drinking during pregnancy. We need to better understand the mechanisms of this dysfunction to determine if there are ways to mitigate the circadian dysfunction and behavioral dysregulation associated with developmental alcohol exposure."

Saturday, April 22, 2006

Sleepwalking with Ambien

Evil Monkey of the Neurotopia blog has a good rundown on the recent finding that patients on Ambien walk and eat in their sleep.

Friday, April 21, 2006

Sleep Photoblogging

I've seen this picture on a gazillion Lefty blogs this morning and was toying with the idea of posting it here with a snarky remark. Now that Sleepdoctor has it up, I cannot be left behind, so here it is:
Vice President, dreaming of quail...

The end of Polyphasic Sleep

Michael Breus PHD, ABSM, of Sleep Disorders Blog looks at Steve Pavlina's end of the Polyphasic Sleep Experiment. From what I've seen, everyone who tried it quit in the end. Nobody lasted long enough for any negative physical consequences to kick-in (phase-shifting the clock several times a day every day for months is most definitely not good for your health in the long term).

They all quit for social reasons - you cannot live out of sync with the family and the rest of the civilization. Read whar Dr.Breus has to say in: Sleep Hacker Backs Off.

Wednesday, April 19, 2006

Clocks in Bacteria III: Evolution of Clocks in Cyanobacteria

As you probably know, my specialty are birds, so writing this series on clocks in microorganisms was quite an eye-opener for me and I have learned a lot. The previous two posts cover the clocks in the cyanobacterium Synechococcus elongatus, the first bacterium in which circadian rhythms were discovered and, thus, the species most studied to date.

The work in Synechococcus has uncovered a cluster of three genes - kaiA, kaiB and kaiC - that are essential for circadian rhytmicity in this species. kaiA positively regulates the kaiBC promoter and overexpression of kaiC represses the kaiBC promoter. Deletion of any one of the three genes leads to the complete loss of rhythmicity.

Synechococcus is a unicellular cyanobacterium. It was thought that circadian clock evolved in it due to incompatibility between nitrogen fixation and photosynthesis. Thus, temporal separation of these two processes was needed, phosynthesis occuring only during the day, while nitrogen fixation was relagated to the night time. It is known that filamentous cyanobacteria, those that build chains of cell, utilize a different strategy, that of spatial separation, some cells being involved in nitrogen fixation and others in photosynthesis. The two cell types exchange the end-results of those processes. Thus, it was thought that filamentous cyanobacteria have no need for a circadian clock.

However, it appears that Synechococcus is not the only bacterium to have a clock. Laboratory of Eviatar Nevo in Israel has taken a look at another cyanobacterium, this time a filamentous, chain-forming species, Nostoc linckia, and the work that ensued suggests that a number of other bacteria may possess a circadian clock as well [1,2,3].
Cyanobacteria are some of the oldest organisms on Earth, at least 3.5 billion years old, appearing in the fossil record relatively soon after the split between Eubacteria and Archaea (3.8 billion years ago). For most of the evolutionary history of cyanobacteria, the environment was very harsh, and UV radiation was one of the major factors influencing the evolution of prokaryotes. For most of that evolutionary history, the environment has undergone large changes, not just in oxygen levels, but also in the levels of UV radiation.

Volodymir Dvornik, Eviatar Nevo and collaborators hypothesized that a circadian clock, involved in temporal processing of light (including UV light) may be an important adaptation in all cyanobacteria and have detected the kaiABC cluster in Nostoc. Moreover, they hypothesized that Nostoc living in harsh, exposed environments (on sun-bathed slopes of so-called Evolution Canyons in Israel) would show greater mutation rate and higher nuclotide polymorphisam in the kai genes than Nostoc living on less harsh slopes of the Canyons. This is exactly what they found [1].

Some of the data from that study was intiguing - suggesting gene duplications and horizontal gene transfer of kai genes. So, they followed this up with a study of kai genes in a number of species of cyanobacteria [2] and later in a number of species of Eubacteria and Archea [3]. Here is the tree of kaiC (right) compared to the tree of 16S rRNA genes (left) - with quite amazing overlap:
Their analysis suggests that kaiC is the oldest element of the complex, while the kaiA is the youngest. kaiA occurs only in cyanobacteria, while kaiB, kaiC and the kaiBC complex occur in other types of bacteria and Archaea. There are also two types of kaiC: short and long. The long, double-domain kaiC (dd-kaiC) is found only in photosynthetic bacteria. Likewise, kaiBC cluster is found only in photosynthetic bacteria. Here is the tree of the kaiBC cluster:
Non-photosynthetis bacteria tend to have the short version of kaiC (sd-kaiC), as well as independent kaiB elsewhere in the genome (i.e., not in a cluster with kaiC). Analysis of the trees of kai gene evolution sugests many duplication events, as well as many occurences of gene loss and horizontal tranfer. Curiously, all the horizontal tranfers occured from cyanobacteria, as donors, to other types of bacteria and Archaea as recipients. Here is the proposed evolutionary history of the kai genes:
Thus, a number of bacteria and Archaea posses one, two or three kai genes, sometimes in multiple copies. Does that mean they have functioning circadian clocks?

Bacteria other than cyanobacteria do not have kaiA. Deletion of kaiA in Synechococcus abolishes rhythms. It is not inconceivable that a different gene (and several additional transcription factors besides kaiA are involved in the Synechococcus clock, so there is no lack of potential candidates) may fulfill that role in other microorganisms. Still, Synechococcus is the only prokaryote in which circadian rhythms have been measured and studied (OK, there is a recent exception - but you will have to wait for the next post to hear about it). Is it possible that kai genes in other bacteria have other functions and only in cynobacteria they got exapted for the circadian role? Time and new research will tell.

Previously in this series:
Circadian Clocks in Microorganisms
Clocks in Bacteria I: Synechococcus elongatus
Clocks in Bacteria II: Adaptive Function of Clocks in Cyanobacteria


[1] Volodymyr Dvornyk, Oxana Vinogradova, and Eviatar Nevo, Long-term microclimatic stress causes rapid adaptive radiation of kaiABC clock gene family in a cyanobacterium, Nostoc linckia, from “Evolution Canyons” I and II, Israel, PNAS, February 19, 2002, vol. 99, no. 4, 2082–2087

[2] Volodymyr Dvornyk, Eviatar Nevo, Evidence for Multiple Lateral Transfers of the Circadian Clock Cluster in Filamentous Heterocystic Cyanobacteria Nostocaceae, JMol Evol (2004) 58:341–347

[3] Volodymyr Dvornyk, Oxana Vinogradova, and Eviatar Nevo, Origin and evolution of circadian clock genes in prokaryotes, PNAS, March 4, 2003, vol. 100, no. 5, 2495–2500

Tuesday, April 18, 2006

ClockNews #38

Asleep or awake we retain memory
Sleeping helps to reinforce what we've learned. And brain scans have revealed that cerebral activity associated with learning new information is replayed during sleep. But, in a study published in the open access journal PLoS Biology, Philippe Peigneux and colleagues at the University of Liege demonstrate for the first time that the brain doesn't wait until night to structure information. Day and night, the brain doesn't stop (re)working what we learn.
The science of lost sleep in teens
"Some of our kids are literally sleep-walking through life, with some potentially serious consequences," Millman said. "As clinicians and researchers, we know more now than ever about the biological and behavioral issues that prevent kids from getting enough sleep. But the National Sleep Foundation did something powerful: They asked teens themselves about their sleep. The results are startling and should be a wake-up call to any parent or pediatrician."
Children who sleep less are three times more likely to be overweight
The less a child sleeps, the more likely he or she is to become overweight, according to researchers from Universit Laval's Faculty of Medicine in an article published in the latest edition of the International Journal of Obesity. The risk of becoming overweight is 3.5 times higher in children who get less sleep than in those who sleep a lot, according to researchers Jean-Philippe Chaput, Marc Brunet, and Angelo Tremblay. These results come from data collected among 422 grade school students aged 5 to 10. The scientists measured the weight, height, and waist size of each participant. Information on the children's lifestyle and socioeconomic status was obtained through phone interviews with their parents.
Sleep apnea treatment benefits the heart
Patients with obstructive sleep apnea have enlarged and thickened hearts that pump less effectively, but the heart abnormalities improve with use of a device that helps patients breathe better during sleep, according to a new study in the April 4, 2006, issue of the Journal of the American College of Cardiology.
Low Stairway to Heaven
SAD arises via fluctuation in melatonin, a chemical produced in response to darkness. Those with SAD suffer from depression during the winter, as the ratio of dark to light hours increases. Melatonin produces a certain drowsiness that causes your circadian rhythms to fall out of sync with the day-night cycles of the environment. Further, some research shows that darkness decreases serotonin levels, which negatively affects mood. Certain SAD sufferers find remedy in “light box treatment”—they expose themselves to artificial light for a few hours a day and become less depressed. I like to think of the steps as my own light box treatment—give me a few hours in front of Low and my mood dramatically improves.
Getting enough Zzzzzs? Kids often don’t
You can force a kid to bed, but you can’t make him fall asleep. Especially if he — or she — is a teenager. It’s not adolescent rebellion. It’s adolescent metabolism. They physically cannot fall asleep because their bodies’ internal clocks are on sort of a chronic daylight-saving time overdrive — which worsens through their teen years, ultimately tapering off in their 20s, according to Leigh Heithoff, clinical specialist with BryanLGH Medical Center West’s Department of Sleep Medicine.
What's holding up the sandman for so many of us?
Unfortunately, with the ease of writing and filling a prescription and the mostly good press these new drugs have gotten to date, millions of people are now taking them without first exploring the reasons for their sleep problems and possible nondrug routes to cure them.
Eye cells that don't see, but regulate
As any good high school biology student can tell you, the human eye sees light with special cells called rods and cones. But when George C. Brainard experimented with shining various colors of light into people's eyes, something odd happened: A specific shade of blue light was most effective at shutting down the body's production of melatonin - the "hormone of darkness" that helps regulate sleep and the body's internal clock. Yet that shade of blue is not one of the colors best detected by rods and cones. His conclusion, shared by others conducting studies on blind people and animals: There must be some unknown cells in the eye - some that responded to light but had nothing to do with seeing. Since that experiment at Thomas Jefferson University, reported in 2001, other scientists have indeed found the new cells, as well as the gene that controls them. Only in the last year has a consensus emerged about how the new cells work.
Sleep has become the new obsession
First it was looks, then weight. Now, the new Western obsession is sleep - or a lack of it. But even experts don't agree on how much people really need
Integrating Transcriptomics and Proteomics
An example of time-shifted discord would be that of the mammalian 24-hour circadian clock, in which regulatory proteins such as Period (mPER) exhibit a four- to eight-hour delay between protein and transcript expression.
Aging-Related Sex Dependent Loss of the Circulating Leptin 24-Hour Rhythm in the Rhesus Monkey
The adipocyte-derived hormone leptin plays a pivotal role in the regulation of body weight and energy homeostasis. Many studies have indicated that the circulating levels of leptin show a 24-h rhythm, but the exact cause and nature of this rhythm is still unclear. In the present study we remotely collected blood samples every h from young and old, male and female rhesus monkeys, and examined their 24-h plasma leptin profiles. In both the young males (10-11 yrs) and young females (7-13 yrs) a clear 24-h plasma leptin rhythm was evident, with a peak occurring ~4 h into the night and a nadir occurring ~1 h into the day (lights on from 0700-1900 h). A 24-h plasma leptin rhythm was also observed in the old males (23-30 yrs), even when they were maintained under constant lighting conditions (continuous dim illumination of ~100 lux). In marked contrast, plasma leptin concentrations were relatively constant across the day and night in old perimenopausal and postmenopausal females (17-24 yrs), regardless of the lighting schedule. These data establish that rhesus monkeys, like humans, show a daily nocturnal rise in plasma leptin, and show that the magnitude of this rhythm undergoes a sex-specific aging-dependent attenuation. Furthermore, they suggest that the underlying endocrine mechanism may be driven in part by a circadian clock mechanism.
Wake-Up Call for Sleep Tech
A bad night's sleep is reason for a very big business. Sleeping pills, led by Ambien, rack up more than $2 billion a year in the United States. Then there is the revenue from overnight stays at sleep clinics, over-the-counter pills, a parade of gimmicks and a thriving business for sleep specialists.
"Sleep is the new sex." So says psychologist Arthur J. Spielman, associate director of the Center for Sleep Disorders Medicine & Research at New York Methodist Hospital in Brooklyn, New York. "People want it, need it, can't get enough of it." The same could be said of profits. Spielman is co-author of The Insomnia Answer (Perigee Books, 2006). He is also developing light-delivering goggles that are supposed to help people reset the circadian rhythms that govern when they nod off and wake up, so they fall asleep faster and stay asleep longer. Sleep is also the new snake oil -- the promise of a good snooze from a book or a bed or a bottle. It's easy pickings.
I'm so tired of being tired
"I'm so tired," said my friend the last time we met for lunch. "The doctor said I have chronic fatigue."
She was not sleeping more than six hours a night, didn't find time to eat well or exercise, and was always achy, so it was not surprising that she felt exhausted. But now there was a label attached to her symptoms that made her feel depressed and alarmed.
CNN Presents Classroom: Sleep: A Dr. Sanjay Gupta Special
Set your VCR to record the CNN Special Classroom Edition: Sleep: A Dr. Sanjay Gupta Special when it airs commercial-free on Monday, April 17, 2006, from approximately 4:10 -- 5:00 a.m. ET on CNN. (A short feature begins at 4:00 a.m. and precedes the program.)
Lighting for the Aging Eye
In the bath, avoid fluorescents, Gilbertson advises. Instead, opt for 100-percent color rendering light bulbs, positioned on either side of your bathroom mirror. Consider installing a dimmer on bathroom lights. Research shows that very low-level regular light, or light in the red spectrum, maximizes night vision while minimizing the disruption of our circadian rhythm, Blitzer says.
Top tips to better sleep
One in three people get less than five hours of sleep a night, according to new research. But Dr John Shneerson, director of the Sleep Centre, Papworth Hospital, Cambridge, says just being aware of some simple tricks can help sleep sufferers achieve a good night's rest. "Sticking to regular bedtimes, helping the body to unwind and avoiding certain foods and drinks in the evening can induce drowsiness and enhance sleep," he says.
Ramelteon Showed Significant Reduction in Time to Fall Asleep With No Evidence of Rebound Insomnia or Withdrawal Effects
Results of a sub-analysis from a phase 3 clinical study showed that Rozerem™ (ramelteon) significantly reduced time to fall asleep in adults with chronic insomnia and showed no evidence of rebound insomnia or withdrawal effects.
Night shift: Late-night work can be bad for your health
According to studies done in the past five years by Harvard University, the National Cancer Institute and the Fred Hutchinson Cancer Research Center in Seattle, women who work the night shift have an increased risk of breast and colorectal cancer. These women have a 60 percent higher risk of breast cancer than women who have never worked nights, the research says. Because of the circadian rhythm -- the 24-hour cycle of sleep and wakefulness -- the body will never be fooled into thinking it's daytime when it's dark out. However, Attarian says there are people who over time can get used to the off-hours. Because of their genetic make-up, Attarian says, some people are just night owls.
Remodeling of astrocytes, a prerequisite for synapse turnover in the adult brain?

A stitch in time, it’s all in the mind
Time slows down in some Kung Fu movie sequences. Jet Li’s foot takes forever to land. Michelle Yeoh’s riposte is glacially slow. This showcases a state-of-the-mind technique called entering the zone: Tai chi masters say this enables aspirants to ‘go faster by going slower.’ While sceptics scoff at such paradoxes, scientists are discovering that, like biofeedback, humans may have more conscious control over their measurement and perception of time than previously thought. Some say this could even lead to chemical cues to shrinking eternity and stretching fleeting moments for those who want to throw away their watch and rock around the clock.
Bed Rest May Not Be Helpful for Threatened Miscarriage
An opinion piece in the March 24 issue of The New York Times highlights a controversial issue in obstetrics: the value of bed rest for threatened miscarriage. Although this intervention is widely prescribed, evidence of its efficacy is limited or absent, and some experts suggest that there may be deleterious effects.
Smart strategies that help you become a beautiful dreamer
Naps can be lifesavers, but if you overdo them, it may be tough to nod off during normal sleeping hours. And you don't want to nap for more than an hour or so at a stretch. "The problem is, when you start getting into two- or three-hour naps, you start resetting your circadian cycle," Dr. Hartse says. (That's your body's internal clock.)

Tuesday, April 11, 2006

REM sleep and paranormal phenomena

Lindsay links to an interesting article in the Washington Post - Near-Death Experiences Linked to Sleep Cycles:
As many as 10 percent of survivors of heart attacks report having a near-death experience -- such as feelings of transcendence, being surrounded by light or floating outside their bodies.

New research announced yesterday suggests a biological explanation for such phenomena: People with near-death experiences are more likely to have different sleep-wake mechanisms in their brains.

In a study comparing 55 people with near-death experiences with 55 people who had no such experiences, neurologist Kevin Nelson of the University of Kentucky found that people who reported such experiences were also more likely to report a phenomenon known as "REM intrusion," where things normally experienced during sleep carry over into wakefulness. REM is an acronym for rapid eye movement, one of the phases of sleep.

Such people wake up but still feel paralyzed or hear sounds that others do not -- as the vestiges of sleep fall away, those experiences disappear. It is not considered a disorder, but merely a variant of the brain's sleep-wake cycle.

Nelson, who published his findings in the journal Neurology, said the extreme fear or feeling of danger brought on by imminent death might trigger the brain mechanism that governs the transition between sleep and wakefulness, leading people to experience various dreamlike phenomena.

The neurologist added that religious and cultural beliefs clearly influenced near-death experiences, and stressed that his findings only spoke to how such a brain mechanism might work, and not why it would work that way.
She also links to the abstract of the paper, a Nature magazine coverage of the connection between near-death experiences and REM sleep and a related article on the connection between sleep paralysis and alien abductions. A year ago, Chris Mooney published a good article on that connection as well:
Our bodies are paralyzed while we undergo REM sleep, and for good reason (lest we act out our dreams and injure ourselves). But in some small number of cases we can actually start to wake up before paralysis wears off, and yet still remain in a dreaming state. What results is hallucination, often of some extremely scary stuff. It appears that humans have always experienced sleep paralysis and sought to explain it, resulting in well known stories of incubi and succubi--demons thought to sexually attack people in their sleep--as well as related tales from other eras and cultures.

Sleepy Americans

Study Shows that Americans are Besieged by Sleeplessness
More and more Americans work and walk around like sleep-deprived zombies, in part due to growing work hours and poor choices made in an environment that is potentially always "on" due to television and the Internet. That's according to a study published last week by the National Academy of Sciences' Institute of Medicine.

The study found that chronic sleep disorders now affect a whopping 50 million to 70 million Americans. Millions more are deprived of sleep on a semi-regular basis. In addition to environment, factors owing to physiology play a role, too. Among other things, more and more Americans are obese, which can interfere with slumber.

The study noted that drug companies are rushing sleep medicines into the sleepless void, targeting the trend as an emerging market. Some 43 million prescriptions for sleep aids were filled last year, and four new drugs will be released over the next year and a half. New sleep centers have sprung up unaccredited throughout the land, tempting Americans. "You can get a sleep study done in a strip mall now without ever meeting with a [qualified] specialist," James Wyatt of the Sleep Disorders Center at Rush University Medical Center in Chicago told the Chicago Tribune.

As noted in the sleep study, the growth in disorders seems to be the product of a failure to deal effectively with environment. That's part of a larger societal trend, say other psychologists. The New York Times ran a piece last week noting that current research shows some 9 percent of Americans suffer from problems related to "high impulsiveness."

Heritability of snoring

Interesting, in today's New York Times:

In the Genes: When the Littlest Family Member Snores, Too
Snoring may be genetic. Children who snore are almost three times as likely as others to have parents who snore. And snoring and sleep-disordered breathing are twice as common in children who test positive for allergies.

Sleep-disordered breathing — snoring is one symptom of it — is associated with poor school performance, cardiovascular troubles and daytime behavioral problems like attention-deficit hyperactivity disorder.

Researchers studied 1-year-old children participating in the Cincinnati Childhood Allergy and Air Pollution Study. Among the 681 children, 105 were habitual snorers — that is, they snored more than three nights a week. The children were also examined for allergies to various foods and other substances using a skin-prick test.

Having a positive allergy test almost doubled the risk for snoring, and having one parent who snored almost tripled the risk. Being African-American more than tripled the risk that a child would be a habitual snorer. The results were published yesterday in the journal Chest.

"If you have a child who snores frequently or loudly," said Dr. Maninder Kalra, an author of the study, "we recommend evaluation by a sleep specialist." Treatment for sleep-disordered breathing in children may involve surgery to remove enlarged tonsils or adenoids, or the use of a breathing device during sleep. Dr. Kalra is an assistant professor of medicine at Cincinnati Children's Hospital Medical Center.

Sleep-disordered breathing can be definitively diagnosed only in a sleep laboratory, and the authors point out that one limitation of their study is that they did not perform this definitive test on each child. Further, the research relied on the reporting of parents, which may not have always been accurate.

Sunday, April 09, 2006

Chossat's Effect in humans and other animals

If you know what Chossat's Effect is, I guess you are a) a physiologist, b) expert in thermoregulation, and c) old. This is term that got expunged from the scientific lexicon a few decades ago, in an effort - correct me if I am wrong on this - spearheaded by the U.S. textbook companies, to replace scientific terminology named after the discoverers (and sometimes even Latin and Greek terms) with bland English neologisms.

But I love Schwann's Cells, Fallopian Tubes (or Mullerian Ducts), Purkinje Fibers, Broca's Area and the amazing Bundle of His! Those terms are memorable, make it easy to sneak in some historical context into teaching science, and have an emotional effect of bringing forth images of ancient scientists working under candlelight, sacrificing their eyesight and health, their social standing and sometimes even their lives, in the feverish hunger for knowledge.

So, what is Chossat's Effect? It comes from a certain 19th century French scientist who was studying the physiology of starvation [1]. The 'modern' term for this effect is "fasting-induced nocturnal hypothernia" (doesn't that sound like something that would prompt the students in the classroom to immediatelly stop paying attention to the teacher and instead pick-up their cell-phones and start text-messaging their friends?).

Actually, this is a very interesting area of research that is very tightly connected to circadian biology. This post is likely to be long, so feel free to skim and just focus on the first part if you are into birds, second part if you are interested in mammals, and the last part if you are into humans.


All warm-blooded animals (and yes, that includes at least some reptiles, not to mention a few heat-producing plants like stink-cabbage) exhibit a daily rhythm of body temperature. If an animal is active during the day (diurnal) and sleeps during the night, reducing the metabolic rate during the night is a good way to save energy.

Some of the smallest birds, like swifts and hummingbirds, need to feed continuously in order to stay alive. At night, when they are not able to forage (flowers are closed, it's hard to see, and owls are hunting at the time), they drop their metabolic rate, and thus body temperature, quite dramatically. The body temperature gets down as low as the environmental temperature, sometimes daringly close to the freezing point. The total drop can be as large as 40 degrees Celsius in some instances! This is called daily torpor (yup, click on that link - it is an excellent blog post) and the metabolic rate drops as much as 95% [2, 3]. This is like full-scale winter hibernation EVERY DAY!

Chossat's effect does not refer to daily torpor, though. It describes a drop in temperature during the night that is larger than the usual circadian fluctuation, in animals undergoing fasting, e.g., during spells of very bad weather (e.g., hurricanes).

Normal amplitude (daily maximum minus nightly minimum) of body temperature in birds with normal access to food ranges between about 1 and 2 degrees Celsius. For instance, a daily maximum may be 41 degrees and the nightly minimum may be 39 degrees (yes, the birds are much warmer than mammals, which makes them inhospitable to microbes that cause many mammalian diseases), which calculates to 2 degrees of amplitude.

During fasting (or food deprivation in the laboratory), the nightly minima drop down to lower levels than in fed birds. The minimum gets lower and lower with each additional night. Importantly, the daily maxima do not change at all. It is thought that it is advantageous for birds to retain their normal metabolic rates during the day so they can immediately resume foraging once the bad weather subsides. Also, if the bad weather persists for too long, the birds need the daytime metabolic rates in order to fly away [4].

According to John Wingfield's "Emergency Life-History Stage" hypothesis [5], an individual's perception of inclement weather directly affect the levels of stress hormones (e.g., corticosterone). An individual who does not perceive the bad weather to be "too bad", will reduce daytime activity and reduce night-time temperature in order to save energy - this individual has made a decision to sit it out.

On the other hand, an individual who perceives bad weather to be "really bad" (or if it lasts too long) will have higher levels of stress hormones and will attempt to fly away during the day. This is not the same mechanism as the seasonal migration, which is usually a nocturnal flight, i.e., they do not experience Zugunruhe, just stress. Stressed birds do not attempt to escape at night, at which time they have allowed their body temperature to drop by several degrees.

Nocturnal hypothermia has been studied in a large number of species of birds (see, for examples, references # 6-12), but most of the work was performed on pigeons [13-15] and quail [16]. Not all avian species exhibit this response. Laurilla at al. [18] write:
"On the other hand, many large birds that are adapted to long fasting periods as a part of their life histories, e.g. penguins and geese (Cherel et al., 1988; Castellini andRea, 1992), owls (Hohtola et al., 1994) and some raptors (McKechnie andLovegrove, 1999) do not show marked hypothermia during fasting. Some species enter hypothermia upon food restriction only when isolated from conspecifics in a laboratory environment, while in the field they remain normothermic by huddling. These observations have even led some authors to question the usefulness of the concept of hypothermia (Lovegrove andSmith, 2003)."[8]

Here is a graphic example of a fasting-induced nocturnal hypothermia in quail (from[17]). The period between the two triangles is the time (3 days) during which the birds had water but no food. Before and after, birds were fed ad libitum. Below is a graph that shows the difference between the temperature minima during the first, second and third day (left) and night (right) of food deprivation in comparison to the last three days and nights of normal feeding prior to the fasting treatment:
Much of the more recent research is looking at other environmental cues that can modify the Chossat's effect, as well as the involvement of the circadian clock in this time-specific form of thermoreguluation. For instance, some of the ambient cues that affect the response include ambient temperature [16, 20], ambient light [17], photoperiod [18, 19], single vs. repeated fasting [18, 19], caloric food restriction vs. complete food deprivation [13], social situation, e.g., opportunity for huddling [8] and presence of stationary vs. flying predators [19, 20]. Here is an example of an effect of ambient temperature on nocturnal hypothermia in fasted pigeons (from [20]). Lower the ambient temperature, deepeer the Chossat's effect:
Here is the effect of the presence of a predator (from [2]). In the presence of a perched hawk (P), nocturnal hypothermia reached normally low levels. In the presence of the flying hawk (F), temperature did not drop as much. Presumably, the pigeons kept the metabolic rate high enough to be able to fly fast if needed:
As stated above, hypothermia occurs only during the night while the temperature during the days remains normal. However, all the studies are performed either in natural conditions of day and night or in light-dark cycles in the laboratory. In constant darkness, the circadian rhythm of temperature persists and hypothermia is apparent. Moreover, the temperature drops both at the minima during the 'subjective night' and at the maxima during the 'subjective day' (from [17]):
This suggests that light has a direct (or "masking") effect on body temperature during the light-phase of the cycle. But is this effect acting directly on the thermoregulatory centers in the hypothalamus or is it mediated by the circadian clock that drives the rhythm of body temperature? In Japanese quail, the circadian pacemakers are located in the eyes. When the eyes are removed [17], both the daily maxima in the light-phase and the nightly minima during the dark phase drop, suggesting that the effect is mediated via the circadian clock, as the light perceived by the photoreceptors in the pineal gland and in the deep brain is incapable of keeping the daily maxima from dropping:

Some small mammals, such as smallest rodents and shrews, exhibit a full-blown daily torpor either normally [21] or in response to fasting [22]. Here is an example of a daily torpor of a mouse-opposum:
In nocturnal animals, which many mammals are, body temperature is high at night when the animals are active and it drops during the day when the animals are sleeping. In rats, fasting induces diurnal hypothermia, i.e., drop of the daily minimum during the day (black circles, compared to pre- and post- treatment values in white symbols) while the nightly maxima remain unaffected [23]:
Chronic caloric food restriction leads to the drop in both the daily minima and nightly maxima of temperature [24].

All the studies until recently have studied responses in relatively small animals (both birds and mammals) with high metabolic rates and high energy needs. But do larger animals, like humans, also exhibit Chossat's effect? After all, the first documented case, that by Chossat himself, was in a dog. This was repeated recently [25]. But even dogs are pretty small compared to humans.

Recently, researchers have addressed this question in a number of species of large mammals, including sheep, goats, horses and yaks [26-29]. Some additional environmental cues were also studied, including the effects of shearing on the circadian temperature rhythm in sheep [30]. Here is a record from a goat:
Notice that, unlike in birds, both the maxima and minima gradually go down.

But, as far as I could find by digging through the literature, nobody has ever performed a similar study in humans. I am assuming that it has been noticed if body temperature drops in fasted humans, but I am not aware of a study systematically addressing this question.


A few years ago I was teaching one of many sections of an Animal Anatomy and Physiology Course. This course requires students to perform a research project. One group of students studied the effects of fasting on body temperature and blood pressure in humans.

They found 8 subjects, all healthy, athletic, non-drinking, non-smoking students ages 19-23. They were instructed to eat normally during the Day1 of the experiment. They subequently spent 36 hours in a house drinking only water and eating nothing. Every four hours, temperature and pressure were measured. By using kids' digital ear thermometers and manual sphigmomanometers they managed, for the most part, not to awaken the subjects during the night. Here are examples of body temperature of three of the subjects - Night1, followed by Day2 and Night 2:

Here are the pooled data for all eight subjects, starting with Day2 and followed by Night1 and Night2 plotted on top of each other for comparison:
Obviously, body temperature of Night2, after a day of fasting, was lower than that of Night1, after the day of normal feeding. I do not have their raw data any more, but if I remember correctly, the data for blood pressure looked very similar. I heard they had a huge breakfast, courtesy of the young researchers, at the end of the experiment.

So, Chossat's Effect appears to be operating in humans as well. Now, this is cool in itself, and I sure hope that someone with access to good clinical lab repeats this study, but there is something else about these data that really excites me. This finding can be used as a tool for studying something entirely different!

The Hypothesis

One of the first demonstrations that humans have daily rhythms involved the time-of-day dependence of time perception. In other words, our subjective "feel" of the speed of passage of time changes systematically with the time of day. At the same time, it has been known for a couple of centuries now that the subjective time perception is also altered during fever. And we know that circadian clock governs daily rhtyhms of body temperature. So, what affects the time perception: time of day or body temperature? If the time passes faster in the evening than at dawn, is it because of the circadian clock acting on the time-perception brain-centers directly, or because we are warmer at the time (which is also driven by the circadian clock)?

This question has haunted circadian researchers for decades and they have devised ever more elaborate experiments to tease the two hypotheses apart, with no avail - we still do not know. But, if by depriving the subjects of food, we can dissociate clock-time from temperature, perhaps we can address this question after all. If the subjective perception of 1 minute (do not use 1 second or 1 hour - those are durations unsuited for this experiment) is similar between the night after a fed day and the night after the fasting day, then the perception is directly driven by the circadian clock. If, on the other hand, perception of a minute changes systematically between the two nights, then we conclude that it is body temperature that affects subjective time perception. Please, someone do this! And if you do, or even if you just want to replicate the Chossat's Effect in humans, I would appreciate it if you would properly cite this post:

Bora Zivkovic, Chossat's Effect in humans and other animals (April 9, 2006), blog Circadiana,


[1] M. Chossat, Sur l'inanition, Paris, 1843

[2] Hiebert, S.M. 1990. Energy costs and temporal organization of torpor in the rufous hummingbird (Selasphorus rufus). Physiological Zoology . 63:1082-1097.

[3] Hiebert, S.M. 1991. Seasonal differences in the response of rufous hummingbirds to food restriction: body mass and the use of torpor. Condor 93:526-537.

[4] Tobias Wang, Carrie C.Y. Hung, David J. Randall, THE COMPARATIVE PHYSIOLOGY OF FOOD DEPRIVATION: From Feast to Famine, Annual Review of Physiology, January 2006, Vol. 68, Pages 223-251

[5] Wingfield, JC; Maney, DL; Breuner, CW; Jacobs, JD; Lynn, S; Ramenofsky, M; Richardson, RD, Ecological bases of hormone-behavior interactions: The "emergency life history stage", American Zoologist [Am. Zool.]. Vol. 38, no. 1, pp. 191-206. 1998.

[6] Tracy A. Maddocks, Fritz Geiser, Energetics, Thermoregulation and Nocturnal Hypothermia in Australian Silvereyes, Condor, Vol. 99, No. 1 (Feb., 1997) , pp. 104-112

[7] Randi Eidsmo Reinertsen and Svein Haftorn, The effect of short-time fasting on metabolism and nocturnal hypothermia in the Willow Tit Parus montanus, Journal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology, Volume 154, Number 1 (January 1984): 23 - 28

[8] Barry G. Lovegrove and Gary A. Smith, Is 'nocturnal hypothermia' a valid physiological concept in small birds?: a study on Bronze Mannikins Spermestes cucullatus, Ibis, Volume 145, Issue 4, Page 547 - October 2003

[9] MacMillen RE, Trost CH., Nocturnal hypothermia in the Inca dove, Scardafella inca, Comp Biochem Physiol. 1967 Oct;23(1):243-53.


[11] Waite, TA, Nocturnal hypothermia in gray jays Perisoreus canadensis wintering in interior Alaska, ORNIS SCAND. Vol. 22, no. 2, pp. 107-110. 1991.

[12] Cécile Thouzeau, Claude Duchamp, and Yves Handrich, Energy Metabolism and Body Temperature of Barn Owls Fasting in the Cold, Physiological and Biochemical Zoology, volume 72 (1999), pages 170–178

[13] Rashotte ME, Henderson D., Coping with rising food costs in a closed economy: feeding behavior and nocturnal hypothermia in pigeons, J Exp Anal Behav. 1988 Nov;50(3):441-56.

[14] R. Graf, S. Krishna and H. C. Heller, Regulated nocturnal hypothermia induced in pigeons by food deprivation, Am J Physiol Regul Integr Comp Physiol 256: R733-R738, 1989

[15] Michael E. Rashotte, Iuri F. Pastukhov, Eugene L. Poliakov, and Ross P. Henderson, Vigilance states and body temperature during the circadian cycle in fed and fasted pigeons (Columba livia), Am J Physiol Regul Integr Comp Physiol 275: R1690-R1702, 1998

[16] Hohtola E, Hissa R, Pyornila A, Rintamaki H, Saarela S., Nocturnal hypothermia in fasting Japanese quail: the effect of ambient temperature, Physiol Behav. 1991 Mar;49(3):563-7.

[17] Herbert Underwood, Christopher T. Steele and Bora Zivkovic, Effects of Fasting on the Circadian Body Temperature Rhythm of Japanese Quail, Physiology & Behavior, Vol. 66, No. 1, pp. 137–143, 1999

[18] Mirja Laurila, Tiina Pilto, Esa Hohtola, Testing the flexibility of fasting-induced hypometabolism in birds: effect of photoperiod and repeated food deprivations, Journal of Thermal Biology 30 (2005) 131–138

[19] MIRJA LAURILA, THERMOREGULATORY CONSEQUENCES OF STARVATION AND DIGESTION IN BIRDS, PhD Dissertation, Faculty of Science, Department of Biology, University of Oulu, 2005 (

[20] Mirja Laurila, Esa Hohtola, The effect of ambient temperature and simulated predation risk on fasting-induced nocturnal hypothermia of pigeons in outdoor conditions, Journal of Thermal Biology 30 (2005) 392–399

[21] Francisco Bozinovic, Gricelda RuÍz, Arturo CortÉs & Mario Rosenmann, Energetics, thermoregulation and torpor in the Chilean mouse-opossum Thylamys elegans (Didelphidae), Revista Chilena de Historia Natural 78: 199-206, 2005

[22] Lovegrove BG, Raman J, Perrin MR., Daily torpor in elephant shrews (Macroscelidea: Elephantulus spp.) in response to food deprivation, J Comp Physiol [B]. 2001 Feb;171(1):11-21.

[23] Kei Nagashima, Sadamu Nakai, Kenta Matsue, Masahiro Konishi, Mutsumi Tanaka, and Kazuyuki Kanosue, Effects of fasting on thermoregulatory processes and the daily oscillations in rats, Am J Physiol Regul Integr Comp Physiol 284: R1486–R1493, 2003.

[24] Yoda T, Crawshaw LI, Yoshida K, Su L, Hosono T, Shido O, Sakudara S, Fukuda Y & Kanosue K (2000) Effects of food deprivation on daily changes in body temperature and behavioural thermoregulation in rats. Am J Physiol 278: R134-R139.

[25] G. Piccione, G. Caola and R. Refinetti, Daily Rhythms of Blood Pressure, Heart Rate, and Body Temperature in Fed and Fasted Male Dogs, J. Vet. Med. A 52, 377–381 (2005)

[26] Giuseppe Piccione, Giovanni Caola, Roberto Refinetti, Circadian rhythms of body temperature and liver function in fed and food-deprived goats, Comparative Biochemistry and Physiology Part A 134 (2003) 563–572

[27] Piccione, G., Caola, G., Refinetti, R., 2002a. Circadian modulation of starvation-induced hypothermia in sheep and goats. Chronobiol. Int. 19, 531–541.

[28] Piccione, G., Caola, G., Refinetti, R., 2002b. The circadian rhythm of body temperature of the horse. Biol. Rhythm Res. 33, 113–119.

[29] Xing-Tai Han, Ao-Yun Xie, Xi-Chao Bi, Shu-Jie Liu and Ling-Hao Hu, Effects of high altitude and season on fasting heat production in the yak Bos grunniens or Poephagus grunniens, British Journal of Nutrition (2002), 88, 189–197

[30] Giuseppe Piccione, Giovanni Caola, and Roberto Refinetti, Effect of shearing on the core body temperature of three breeds of Mediterranean sheep, Small Ruminant Research 46 (2002) 211–215

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